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Sample records for bone resorbing activity

  1. Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts

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    Kwon, Jun-Oh; Lee, Yong Deok; Kim, Haemin; Kim, Min Kyung; Song, Min-Kyoung; Lee, Zang Hee; Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr

    2016-09-02

    Tetraspanin family proteins regulate morphology, motility, fusion, and signaling in various cell types. We investigated the role of the tetraspanin 7 (Tspan7) isoform in the differentiation and function of osteoclasts. Tspan7 was up-regulated during osteoclastogenesis. When Tspan7 expression was reduced in primary precursor cells by siRNA-mediated gene knock-down, the generation of multinuclear osteoclasts was not affected. However, a striking cytoskeletal abnormality was observed: the formation of the podosome belt structure was inhibited and the microtubular network were disrupted by Tspan7 knock-down. Decreases in acetylated microtubules and levels of phosphorylated Src and Pyk2 in Tspan7 knock-down cells supported the involvement of Tspan7 in cytoskeletal rearrangement signaling in osteoclasts. This cytoskeletal defect interfered with sealing zone formation and subsequently the bone-resorbing activity of mature osteoclasts on dentin surfaces. Our results suggest that Tspan7 plays an important role in cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules. - Highlights: • Tspan7 expression is up-regulated during osteoclastogenesis. • Tspan7 regulates podosome belt organization in osteoclasts. • Tspan7 is crucial for sealing zone formation and bone-resorption by osteoclasts. • Src and Pyk2 phosphorylation and microtubule acetylation mediate Tspan7 function.

  2. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines

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    Huang, Qiang; Gao, Bo; Wang, Long; Hu, Ya-Qian; Lu, Wei-Guang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian, E-mail: liujianhq@sina.com

    2014-11-01

    Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H{sub 2}O{sub 2}) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARγ2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis. - Highlights: • Myricitrin protects MC3T3-E1 cells and hBMSCs from oxidative stress. • It is accompanied by a decrease in oxidative stress and bone-resorbing cytokines. • Myricitrin decreases serum reactive oxygen species to some degree. • Myricitrin partly reverses ovariectomy effects in vivo. • Myricitrin may represent a beneficial anti-osteoporosis treatment method.

  3. Resorbable screws for fixation of autologous bone grafts

    NARCIS (Netherlands)

    Raghoebar, GM; Liem, RSB; Bos, RRM; van der Wal, JE; Vissink, A

    The aim of this study was to evaluate the suitability of resorbable screws made of poly (D,L-lactide) acid (PDLLA) for fixation of autologous bone grafts related to graft regeneration and osseointegration of dental implants. In eight edentulous patients suffering from insufficient retention of their

  4. Resorbable bioactive ceramic for treatment of bone infection.

    Science.gov (United States)

    El-Ghannam, Ahmed; Jahed, Kiarash; Govindaswami, Meera

    2010-07-01

    Polymethylmethacrylate (PMMA) beads have been widely used in the treatment of bone infection over the last three decades. Although PMMA does offer a mechanism to quickly and effectively administer a localized dose of antibiotic to the site of infection, its efficacy is limited by its nonresorbability and nonbioactivity. Resorbable bioactive silica-calcium phosphate nanocomposite (SCPC75) was investigated as a novel controlled release carrier of vancomycin for the treatment of osteomyelitis. SCPC75 particles adsorbed significantly higher amount of vancomycin compared with PMMA. Moreover, SCPC75 provided a sustained release kinetics of therapeutic dose of vancomycin up to 35 days. The novel resorbable ceramic was able to release 95.5% of the adsorbed drug in an average dose of 12 microg/mL/day over 480 h (35 days). In conjunction with the sustained drug release, a controlled dissolution rate that led to 40% mass loss of SCPC75 was observed. On the other hand, PMMA provided a sustained release of a therapeutic dose of vancomycin for 14 days after which minimal concentration of the drug was detected. Moreover, PMMA retained 32% of the drug adsorbed onto its surface. The SCPC-vancomycin implant can serve a dual function: provide a sustained therapeutic dose of antibiotic to eradicate infection and stimulate bone cell differentiation and new bone formation. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

  5. The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts.

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    Bas ten Harkel

    Full Text Available Foreign body multinucleated giant cells (FBGCs and osteoclasts share several characteristics, like a common myeloid precursor cell, multinuclearity, expression of tartrate-resistant acid phosphatase (TRAcP and dendritic cell-specific transmembrane protein (DC-STAMP. However, there is an important difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form only under pathological conditions or at the surface of foreign materials, like medical implants. Despite similarities, an important distinction between these cell types is that osteoclasts can resorb bone, but it is unknown whether FBGCs are capable of such an activity. To investigate this, we differentiated FBGCs and osteoclasts in vitro from their common CD14+ monocyte precursor cells, using different sets of cytokines. Both cell types were cultured on bovine bone slices and analyzed for typical osteoclast features, such as bone resorption, presence of actin rings, formation of a ruffled border, and characteristic gene expression over time. Additionally, both cell types were cultured on a biomimetic hydroxyapatite coating to discriminate between bone resorption and mineral dissolution independent of organic matrix proteolysis. Both cell types differentiated into multinucleated cells on bone, but FBGCs were larger and had a higher number of nuclei compared to osteoclasts. FBGCs were not able to resorb bone, yet they were able to dissolve the mineral fraction of bone at the surface. Remarkably, FBGCs also expressed actin rings, podosome belts and sealing zones--cytoskeletal organization that is considered to be osteoclast-specific. However, they did not form a ruffled border. At the gene expression level, FBGCs and osteoclasts expressed similar levels of mRNAs that are associated with the dissolution of mineral (e.g., anion exchange protein 2 (AE2, carbonic anhydrase 2 (CAII, chloride channel 7 (CIC7, and vacuolar-type H+-ATPase (v-ATPase, in contrast the matrix degrading

  6. Bacteroides gingivalis antigens and bone resorbing activity in root surface fractions of periodontally involved teeth

    International Nuclear Information System (INIS)

    Patters, M.R.; Landsberg, R.L.; Johansson, L.-A.; Trummel, C.L.; Robertson, P.R.

    1982-01-01

    Bone resorbing activity and the presence of antigens of Bacteroides gingivalis were assessed in plaque, calculus, cementum, and dentin obtained from roots of teeth previously exposed to periodontitis. Each fraction was obtained by scaling the root surface. The fraction were extracted by stirring and sonication, and the soluble centrifuged, sterilized, dialyzed, and adjusted to equivalent protein concentrations. Cementum and dentin extracts from impacted teeth were prepared similarly and served as controls. Stimulation of bone resorption by each extract was assessed in organ cultures of fetal rat bones by measurement of release of previously-incorporated 45 Ca from the bone into the medium. In some groups of teeth, calculus and cementum were treated with acid prior to scaling. Citric acid washes were recovered and dialyzed. An enzyme-linked immunosorbent assay (ELISA) was used to assess the extracts for the presence of antigens reactive with an antiserum to B. gingivalis. Significant stimulation of bone resorption was found in all calculus and periodontally-involved cementum preparations. ELISA showed significant levels of B.gingivalis antigens in plaque, calculus, and cementum of periodontally-involved teeth, but not in involved dentin nor in cementum or dentin of impact teeth. Treatment with citric acid removed essentially all B.gingivalis antigens from cementum but not calculus. The results suggest that substances which stimulate bone resorption and substances which react with B. gingivalis antiserum are present in surface plaque, calculus, and cementum or periodontally-involved teeth. These substances are not present in cementum and dentin of impacted teeth nor in dentin of periodontally-involved teeth. Treatment by both scaling and citric demineralization will remove most of these substances from cementum of teeth previously exposed to periodontitis. (author)

  7. Bacteroides gingivalis antigens and bone resorbing activity in root surface fractions of periodontally involved teeth

    Energy Technology Data Exchange (ETDEWEB)

    Patters, M R; Landsberg, R L; Johansson, L A; Trummel, C L; Robertson, P R [Department of Periodontology, University of Connecticut, School of Dental Medicine, Farmington, Connecticut, U.S.A.

    1982-01-01

    Bone resorbing activity and the presence of antigens of Bacteroides gingivalis were assessed in plaque, calculus, cementum, and dentin obtained from roots of teeth previously exposed to periodontitis. Each fraction was obtained by scaling the root surface. The fraction were extracted by stirring and sonication, and the soluble centrifuged, sterilized, dialyzed, and adjusted to equivalent protein concentrations. Cementum and dentin extracts from impacted teeth were prepared similarly and served as controls. Stimulation of bone resorption by each extract was assessed in organ cultures of fetal rat bones by measurement of release of previously-incorporated /sup 45/Ca from the bone into the medium. In some groups of teeth, calculus and cementum were treated with acid prior to scaling. Citric acid washes were recovered and dialyzed. An enzyme-linked immunosorbent assay (ELISA) was used to assess the extracts for the presence of antigens reactive with an antiserum to B. gingivalis. Significant stimulation of bone resorption was found in all calculus and periodontally-involved cementum preparations. ELISA showed significant levels of B.gingivalis antigens in plaque, calculus, and cementum of periodontally-involved teeth, but not in involved dentin nor in cementum or dentin of impact teeth. Treatment with citric acid removed essentially all B.gingivalis antigens from cementum but not calculus. The results suggest that substances which stimulate bone resorption and substances which react with B. gingivalis antiserum are present in surface plaque, calculus, and cementum or periodontally-involved teeth. These substances are not present in cementum and dentin of impacted teeth nor in dentin of periodontally-involved teeth. Treatment by both scaling and citric demineralization will remove most of these substances from cementum of teeth previously exposed to periodontitis.

  8. Comparative analysis of guided bone regeneration using autogenous tooth bone graft material with and without resorbable membrane

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    Ji-Young Lee

    2013-09-01

    Conclusion: Both groups showed clinically acceptable bone regeneration without any eventful complications. Within the limitation of this study, we can carefully conclude that the use of resorbable membrane is not a critical factor in GBR when using AutoBT.

  9. Negative effect of rapidly resorbing properties of bioactive glass-ceramics as bone graft substitute in a rabbit lumbar fusion model.

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    Lee, Jae Hyup; Ryu, Hyun-Seung; Seo, Jun-Hyuk; Lee, Do-Yoon; Chang, Bong-Soon; Lee, Choon-Ki

    2014-03-01

    Bioactive glass-ceramics have the ability to directly bind to bones and have been widely used as bone graft substitutes due to their high osteoconductivity and biocompatibility. CaO-SiO2-P2O5-B2O3 glass-ceramics are known to have good osteoconductivity and are used as bone graft extenders. This study aimed to evaluate the effects of the resorbing properties of glass-ceramics in bone fusion after producing and analyzing three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with high osteoconductivity that had enhanced resorption by having an increased B2O3 content. The three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with B2O3 contents of 8.0, 9.0, and 9.5 weight % were designated and grouped as P20B80, P10B90, and P5B95, respectively. Glass-ceramic types were tested for fusion rates and bone formation by employing the lumbar 5-6 intertransverse process fusion model in 51 New Zealand male rabbits. Bioactivity was assessed by soaking in simulated body fluid (SBF). In vitro study results showed sufficient hydroxycarbonate apatite layer formation occurred for P20B80 in1 day, for P10B90 in 3 days, and for P5B95 in 5 days after soaking in SBF. For the rabbit lumbar spine posterolateral fusion model, the autograft group recorded a 100% fusion rate with levels significantly higher than those of P20B80 (29.4%), P10B90 (0%), and P5B95 (14.3%), with high resorbing properties. Resorbing property differences among the three glass-ceramic groups were not significant. Histological results showed new bone formation confirming osteoconductivity in all three types of glass-ceramics. Radiomorphometric results also confirmed the resorbing properties of the three glass-ceramic types. The high resorbing properties and osteoconductivity of porous glass-ceramics can be advantageous as no glass-ceramics remain in the body. However, their relatively fast rate of resorption in the body negatively affects their role as an osteoconductive scaffold as glass-ceramics are resorbed before bony fusion.

  10. Dilemma in pediatric mandible fractures: resorbable or metallic plates?

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    Taylan Filinte, Gaye; Akan, İsmail Mithat; Ayçiçek Çardak, Gülçin Nujen; Özkaya Mutlu, Özay; Aköz, Tayfun

    2015-12-01

    The aim of this study was to compare the efficiency of resorbable and metallic plates in open reduction and internal fixation of mandible fractures in children. Thirty-one patients (mean age, 8.05 years; range 20 months-14 years) were operated on various fractures of the mandible (26 [60.4%] symphysis- parasymphysis, 12 [27.9%] condylar-subcondylar fractures, 5 [11.6%] angulus and ramus fractures). Twelve patients were treated with resorbable plates and 19 patients with metallic plates. Mean follow-up time was 41 months (11-74 months) in the metallic hardware group and was 22 months (8-35 months) in the resorbable plate group. Both groups were investigated for primary bone healing, complications, number of operations, and mandibular growth. The results were discussed below. Both groups demonstrated primary bone healing. Minor complications were similar in both groups. The metallic group involved secondary operations for plate removal. Mandibular growth was satisfactory in both groups. Resorbable plates cost more than the metallic ones; however, when the secondary operations are included in the total cost, resorbable plates were favourable. As mandibular growth and complication parameters are similar in both groups, resorbable plates are favored due to avoidance of potential odontogenic injury, elimination of long-term foreign body retention and provision of adequate stability for rapid bone healing. However, learning curve and concerns for decreased stability against heavy forces of mastication accompanied with the resorbable plates when compared to the metallic ones should be kept in mind.

  11. Investigation of novel bioactive rapidly resorbable bone substitute materials and their influence on osteoblastic cell differentiation in vivo

    OpenAIRE

    Jonscher, Sebastian

    2010-01-01

    Among the various techniques to reconstruct or enlarge a deficient alveolar ridge, the concept of guided bone regeneration (GBR) has become a predictable and well-documented surgical approach. At present, autogenous bone grafts are preferably combined with barrier membranes. Using synthetic biodegradable bone substitute materials, however, is advantageous, since it avoids second-site surgery for autograft harvesting. A bone substitute for alveolar ridge augmentation must be rapidly resorbable...

  12. Novel resorbable glass-ceramic scaffolds for hard tissue engineering: from the parent phosphate glass to its bone-like macroporous derivatives.

    Science.gov (United States)

    Bretcanu, Oana; Baino, Francesco; Verné, Enrica; Vitale-Brovarone, Chiara

    2014-05-01

    One of the major challenges of hard tissue engineering research focuses on the development of scaffolds that can match the mechanical properties of the host bone and resorb at the same rate as the bone is repaired. The aim of this work was the synthesis and characterization of a resorbable phosphate glass, as well as its application for the fabrication of three dimensional (3-D) scaffolds for bone regeneration. The glass microstructure and behaviour upon heating were analysed by X-ray diffraction, differential scanning calorimetry and hot stage microscopy. The glass solubility was investigated according to relevant ISO standards using distilled water, simulated body fluid (SBF) and Tris-HCl as testing media. The glass underwent progressive dissolution over time in all three media but the formation of a hydroxyapatite-like layer was also observed on the samples soaked in SBF and Tris-HCl, which demonstrated the bioactivity of the material. The glass powder was used to fabricate 3-D macroporous bone-like glass-ceramic scaffolds by adopting polyethylene particles as pore formers: during thermal treatment, the polymer additive was removed and the sintering of glass particles was allowed. The obtained scaffolds exhibited high porosity (87 vol.%) and compressive strength around 1.5 MPa. After soaking for 4 months in SBF, the scaffolds mass loss was 76 wt.% and the pH of the solution did not exceed the 7.55 value, thereby remaining in a physiological range. The produced scaffolds, being resorbable, bioactive, architecturally similar to trabecular bone and exhibiting interesting mechanical properties, can be proposed as promising candidates for bone repair applications.

  13. The Role of Resorbable Plate and Artificial Bone Substitute in Reconstruction of Large Orbital Floor Defect

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    Ho Kwon

    2016-01-01

    Full Text Available It is essential to reduce and reconstruct bony defects adequately in large orbital floor fracture and defect. Among many reconstructive methods, alloplastic materials have attracted attention because of their safety and ease of use. We have used resorbable plates combined with artificial bone substitutes in large orbital floor defect reconstructions and have evaluated their long-term reliability compared with porous polyethylene plate. A total of 147 patients with traumatic orbital floor fracture were included in the study. Surgical results were evaluated by clinical evaluations, exophthalmometry, and computed tomography at least 12 months postoperatively. Both orbital floor height discrepancy and orbital volume change were calculated and compared with preoperative CT findings. The average volume discrepancy and vertical height discrepancies were not different between two groups. Also, exophthalmometric measurements were not significantly different between the two groups. No significant postoperative complication including permanent diplopia, proptosis, and enophthalmos was noted. Use of a resorbable plate with an artificial bone substitute to repair orbital floor defects larger than 2.5 cm2 in size yielded long-lasting, effective reconstruction without significant complications. We therefore propose our approach as an effective alternative method for large orbital floor reconstructions.

  14. Relative accretion of /sup 99m/Tc-polyphosphate by forming and resorbing bone systems in rats: its significance in the pathologic basis of bone scanning

    International Nuclear Information System (INIS)

    Garcia, D.A.; Tow, D.E.; Kapur, K.K.; Wells, H.

    1976-01-01

    The relative roles of osteogenesis and osteolysis in the production of positive radionuclide images of skeletal lesions were investigated. The uptake of /sup 99m/Tc-polyphosphate (Tc-PP) by each process was measured in an animal model that permitted bone formation and resorption to be studied independently. Ten rats received intramuscular implants of bone-forming demineralized matrix (DM) and resorbing devitalized bone (DV). Radiographs and Tc-PP scintiscans were made each week thereafter. At 6 to 10 weeks, the implants and normal bone samples were removed, counted for /sup 99m/Tc, and examined histologically. The uptake of Tc-PP by DM implants was first detected on images made 3 weeks after implantation, and by DV implants, 1 to 2 weeks later. Serial radiography showed progressive calcification of DM and resorption of DV implants. Microscopic examinations of undecalcified sections, stained with a modified Goldner preparation, revealed vital-bone formation in the DM implants and osteoclastic resorption in the DV. Activity counts per gram of DM and DV implants were, respectively, 200 percent and 90 percent that of normal bone. Since only the bone-forming system (DM) accumulated Tc-PP at greater than normal concentrations, this study indicates that positive bone images of osteolytic lesions solely reflect compensatory osteogenic responses

  15. The impact of thickness of resorbable membrane of human origin on the ossification of bone defects: A pathohistologic study

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    Bubalo Marija

    2012-01-01

    Full Text Available Background/Aim. A wide range of resorbable and nonresorbable membranes have been investigated over the last two decades. The barrier membrane protects the defect from ingrowth of soft tissue cells and allows bone progenitor cells to develop bone within a blood clot that is formed beneath the barrier membrane. The membranes are applied to reconstruct small bony defect prior to implantation, to cover dehiscences and fenestrations around dental implants. The aim of this study was to evaluate the influence of human resorbable demineralized membrane (RHDM thickness on bone regeneration. Methods. The experiment, approved by Ethical Committee, was performed on 6 dogs and conducted into three phases. Bone defects were created in all the 6 dogs on the left side of the mandible, 8 weeks after extraction of second, third and fourth premolars. One defect was covered with RHDM 100 μ thick, one with RHDM 200 μ thick, and the third defect left empty (control defect. The histopathological analysis was done 2, 4 and 6 months after the surgery. In the third phase samples of bone tissue were taken and subjected to histopathological analysis. Results. In all the 6 dogs the defects treated with RHDM 200 μ thick showed higher level of bone regeneration in comparison with the defect treated with RHDM 100 μ thick and especially with empty defect. Conclusion. Our results demonstrated that the thicker membrane showed the least soft tissue ingrowths and promoted better bone formation at 6 months compared with a thinner one.

  16. The biphasic effect of triiodothyronine compared to bone resorbing effect of PTH on bone modelling of mouse long bone in vitro

    International Nuclear Information System (INIS)

    Soskolne, W.A.; Schwartz, Z.; Goldstein, M.; Ornoy, A.

    1990-01-01

    To examine the effects of T3 on fetal long bone modelling the radii and ulnae of 16 day old fetal mice were grown in vitro for two days. Their growth, mineralization, and resorption were assessed by measuring diaphyseal length, calcium and phosphorus content, hydroxyproline content, and the release of incorporated 45 Ca. The effects of T3 were compared to the effects of 1-34 PTH, a known resorbing agent, on the same system. Devitalized bones were used as a control. The results showed that T3 had a biphasic effect. At high concentrations (10(-5) M-10(-6) M) T3 inhibited the growth of the bones as indicated by their diaphyseal length and hydroxyproline content. Calcium and phosphorus content were significantly decreased while 45 Ca release was increased. Similar effects were also found after the addition of 1-34 PTH to the media. However, T3, at lower concentrations (10(-7) M-10(-9) M), stimulated the growth and calcification of the bones as indicated by an increase in diaphyseal length and the hydroxyproline, calcium, and phosphorus content. 45 Ca release was significantly decreased at these concentrations. Neither T3 nor 1-34 PTH affected devitalized bones in the same system. The results suggest that at physiological concentrations, T3 has a direct, anabolic effect on bone, which may explain its major role in the growth process of various species. At high doses, however, T3 stimulates bone resorption in a way similar to PTH

  17. [Our experience about the use of resorbable plates in the treatment of craniostenosis].

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    Grassiot, B; Delabar, V; Szathmari, A; Beuriat, P A; Paulus, C; Mottolese, C

    2015-09-01

    The use of resorbable plates increases for craniosynostosis surgery. This material, based on polymere (PLA, PGA) can replace steel wire and non resorbable plates. A few studies present surgical results about the use of this material with a long follow-up. We present our ten years experience of using resorbable material for craniosynostosis treatment in children. Between 2002 and 2012, we operated 283 craniosynostosis (98 scaphocephalies, 55 trigonocephalies, 79 plagiocephalies et 51 craniofaciostenoses). Among these surgeries, 211 were realized with resorbable material (plates and screws). Different criteria were observed: the esthetic result, the infection rate, the re-intervention, the bone defects and the inflammatory granuloma. Among the 211 craniosynostosis, we found 62 plagiocephalies, 66 scaphocephalies, 50 trigonocephalies, 33 craniofaciostenoses. All the reconstructions were realized with the same resorbable material (Macropore by Medtronic). The rate of complications was low: one scar infection without participation of material for two patients (0.9%), a pseudo-meningocele for two patients (0.9%), epilepsy for four children (1.8%) and bone defect for 15 (7%). We observed no granuloma for these patients. Our experience of ten years using resorbable material is very satisfactory. This material permits to realize solid and esthetic reconstructions with a low rate of infection without dangerous reaction for children in young age. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Treatment of intrabony defects with resorbable materials, non-resorbable materials and flap debridement.

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    Zybutz, M D; Laurell, L; Rapoport, D A; Persson, G R

    2000-03-01

    Different types of barriers are used in guided tissue regenerative procedures. This prospective study compared resorbable citric acid ester softened polylactic acid membranes (RM) and non-resorbable expanded polytetrafluoroethylene (ePTFE) barriers (NRM) in GTR treatment of intrabony defects. 29 subjects were randomly assigned to the RM group or NRM group. Each patient received one GTR procedure. An open flap debridement (FD) was performed at another site 2 weeks later to evaluate healing potential. Clinical treatment outcomes were finally evaluated 12 months after surgery for changes of pocket depth PD, probing attachment level PAL, and probing bone level PBL, and radiographically for bone change using standardised radiographs. No differences in healing patters after surgery were found between patients in the 2 study groups as evaluated from the FD surgical procedures. NRM treated sites showed less signs of post-surgical inflammation during the 1st 4 weeks of healing than did RM treated sites (p<0.05). GTR-treated defects in the RM group, initially 7.0+/-2.2 mm deep, showed PD reduction of 3.3+/-2.2 mm, PAL gain of 2.4+/-1.8 mm, PBL gain of 2.4+/-3.7 mm (28%) and a radiographic bone fill of 2.3+/-2.4 mm. Defects treated with the NRM exhibited PD reduction of 3.1+/-2.1 mm, PAL gain of 2.4+/-0.8 mm, PBL gain of 2.2+/-1.7 mm (25%) and a radiographic bone fill of 3.3+/-2.2 mm. All improvements were statistically significant (p<0.01) but there was no difference between RM and NRM treatments for any of the efficacy variables. The results of this study indicated that there was no clinically significant difference in treatment outcomes following GTR treatment of intrabony defects with citric acid ester softened polylactic acid membranes as compared to ePTFE barriers. The overall mean inter-proximal vertical bone defect fill at 12 months as assessed from intra-oral radiographs was 44% of the original mean defect depth. Thus, no clinically significant difference in

  19. Resorbable versus titanium plates for orthognathic surgery.

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    Agnihotry, Anirudha; Fedorowicz, Zbys; Nasser, Mona; Gill, Karanjot S

    2017-10-04

    Recognition of some of the limitations of titanium plates and screws used for the fixation of bones has led to the development of plates manufactured from bioresorbable materials. Whilst resorbable plates appear to offer clinical advantages over metal plates in orthognathic surgery, concerns remain about the stability of fixation and the length of time required for their degradation and the possibility of foreign body reactions. This review compares the use of titanium versus bioresorbable plates in orthognathic surgery and is an update of the Cochrane Review first published in 2007. To compare the effects of bioresorbable fixation systems with titanium systems used during orthognathic surgery. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 January 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11) in the Cochrane Library (searched 20 January 2017); MEDLINE Ovid (1946 to 20 January 2017); and Embase Ovid (1980 to 20 January 2017). We searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 20 January 2017), and the World Health Organization International Clinical Trials Registry Platform (searched 20 January 2017) for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials comparing bioresorbable versus titanium fixation systems used for orthognathic surgery in adults. Two review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias of the included studies. We resolved disagreement by discussion. Clinical heterogeneity between the included trials precluded pooling of data, and only a descriptive summary is presented. This review included two trials, involving 103 participants, one comparing titanium with resorbable plates and screws and

  20. Assessment of Bonelike (registered) graft with a resorbable matrix using an animal model

    International Nuclear Information System (INIS)

    Lobato, J.V.; Hussain, N. Sooraj; Botelho, C.M.; Mauricio, A.C.; Afonso, A.; Ali, N.; Santos, J.D.

    2006-01-01

    Synthetic bone grafts have been developed to provide an alternative to autografts and allografts. Bonelike (registered) is a patented synthetic osteoconductive bone graft that mimics the mineral composition of natural bone. In the present preliminary animal studies a user-friendly version of synthetic bone graft Bonelike (registered) have been developed by using a resorbable matrix, Floseal (registered) , as a vehicle and raloxifene hydrochloride as a therapeutic molecule, that is known to decrease osteoclast activity and therefore enhanced bone formation. From histological and scanning electron microscopy evaluations, the use of Bonelike (registered) associated with Floseal (registered) and raloxifene hydrochloride showed that new bone was rapidly apposed on implanted granules and also that the presence of the matrix and therapeutic molecule does not alter the proven highly osteoconductivity properties of Bonelike (registered) . Therefore, this association may be one step-forward for the clinical applications of Bonelike (registered) scaffolds since it is much more easy-to-handle when compared to granular materials

  1. Design and Optimization of Resorbable Silk Internal Fixation Devices

    Science.gov (United States)

    Haas, Dylan S.

    Limitations of current material options for internal fracture fixation devices have resulted in a large gap between user needs and hardware function. Metal systems offer robust mechanical strength and ease of implantation but require secondary surgery for removal and/or result in long-term complications (infection, palpability, sensitivity, etc.). Current resorbable devices eliminate the need for second surgery and long-term complications but are still associated with negative host response as well as limited functionality and more difficult implantation. There is a definitive need for orthopedic hardware that is mechanically capable of immediate fracture stabilization and fracture fixation during healing, can safely biodegrade while allowing complete bone remodeling, can be resterilized for reuse, and is easily implantable (self-tapping). Previous work investigated the use of silk protein to produce resorbable orthopedic hardware for non- load bearing fracture fixation. In this study, silk orthopedic hardware was further investigated and optimized in order to better understand the ability of silk as a fracture fixation system and more closely meet the unfulfilled market needs. Solvent-based and aqueous-based silk processing formulations were cross-linked with methanol to induce beta sheet structure, dried, autoclaved and then machined to the desired device/geometry. Silk hardware was evaluated for dry, hydrated and fatigued (cyclic) mechanical properties, in vitro degradation, resterilization, functionalization with osteoinductive molecules and implantation technique for fracture fixation. Mechanical strength showed minor improvements from previous results, but remains comparable to current resorbable fixation systems with the advantages of self-tapping ability for ease of implantation, full degradation in 10 months, ability to be resterilized and reused, and ability to release molecules for osteoinudction. In vivo assessment confirmed biocompatibility, showed

  2. Bone apatite composition of necrotic trabecular bone in the femoral head of immature piglets.

    Science.gov (United States)

    Aruwajoye, Olumide O; Kim, Harry K W; Aswath, Pranesh B

    2015-04-01

    Ischemic osteonecrosis of the femoral head (IOFH) can lead to excessive resorption of the trabecular bone and collapse of the femoral head as a structure. A well-known mineral component to trabecular bone is hydroxyapatite, which can be present in many forms due to ionic substitution, thus altering chemical composition. Unfortunately, very little is known about the chemical changes to bone apatite following IOFH. We hypothesized that the apatite composition changes in necrotic bone possibly contribute to increased osteoclast resorption and structural collapse of the femoral head. The purpose of this study was to assess the macroscopic and local phosphate composition of actively resorbed necrotic trabecular bone to isolate differences between areas of increased osteoclast resorption and normal bone formation. A piglet model of IOFH was used. Scanning electron microscopy (SEM), histology, X-ray absorbance near edge structure (XANES), and Raman spectroscopy were performed on femoral heads to characterize normal and necrotic trabecular bone. Backscattered SEM, micro-computed tomography and histology showed deformity and active resorption of necrotic bone compared to normal. XANES and Raman spectroscopy obtained from actively resorbed necrotic bone and normal bone showed increased carbonate-to-phosphate content in the necrotic bone. The changes in the apatite composition due to carbonate substitution may play a role in the increased resorption of necrotic bone due to its increase in solubility. Indeed, a better understanding of the apatite composition of necrotic bone could shed light on osteoclast activity and potentially improve therapeutic treatments that target excessive resorption of bone.

  3. Preparation and Characterization of Resorbable Bacterial Cellulose Membranes Treated by Electron Beam Irradiation for Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Sung-Jun An

    2017-10-01

    Full Text Available Bacterial cellulose (BC is an excellent biomaterial with many medical applications. In this study, resorbable BC membranes were prepared for guided bone regeneration (GBR using an irradiation technique for applications in the dental field. Electron beam irradiation (EI increases biodegradation by severing the glucose bonds of BC. BC membranes irradiated at 100 kGy or 300 kGy were used to determine optimal electron beam doses. Electron beam irradiated BC membranes (EI-BCMs were evaluated by scanning electron microscopy (SEM, attenuated total reflectance-Fourier transform infrared (ATR-FTIR spectroscopy, thermal gravimetric analysis (TGA, and using wet tensile strength measurements. In addition, in vitro cell studies were conducted in order to confirm the cytocompatibility of EI-BCMs. Cell viabilities of NIH3T3 cells on 100k and 300k EI-BCMs (100 kGy and 300 kGy irradiated BC membranes were significantly greater than on NI-BCMs after 3 and 7 days (p < 0.05. Bone regeneration by EI-BCMs and their biodegradabilities were also evaluated using in vivo rat calvarial defect models for 4 and 8 weeks. Histometric results showed 100k EI-BCMs exhibited significantly larger new bone area (NBA; % than 300k EI-BCMs at 8 weeks after implantation (p < 0.05. Mechanical, chemical, and biological analyses showed EI-BCMs effectively interacted with cells and promoted bone regeneration.

  4. A Novel Procedure for the Immediate Reconstruction of Severely Resorbed Alveolar Sockets for Advanced Periodontal Disease.

    Science.gov (United States)

    Aimetti, Mario; Manavella, Valeria; Cricenti, Luca; Romano, Federica

    2017-01-01

    Background. Several clinical techniques and a variety of biomaterials have been introduced over the years in an effort to overcome bone remodeling and resorption after tooth extraction. However, the predictability of these procedures in sockets with severely resorbed buccal/lingual plate due to periodontal disease is still unknown. Case Description. A patient with advanced periodontitis underwent extraction of upper right lateral and central incisors. The central incisor exhibited complete buccal bone plate loss and a 9 mm vertical bone deficiency on its palatal side. The alveolar sockets were filled with collagen sponge and covered with a nonresorbable high-density PTFE membrane. Primary closure was not attained and any rigid scaffold material was not used. Histologic analysis provided evidence of new bone formation. At 12 months a cone-beam computed tomographic scan revealed enough bone volume to insert two conventional dental implants in conjunction with minor horizontal bone augmentation procedures. Clinical Implications. This case report would seem to support the potential of the proposed reconstructive approach in changing the morphology of severely resorbed alveolar sockets, minimizing the need for advanced bone regeneration procedures during implant placement.

  5. A Novel Procedure for the Immediate Reconstruction of Severely Resorbed Alveolar Sockets for Advanced Periodontal Disease

    Directory of Open Access Journals (Sweden)

    Mario Aimetti

    2017-01-01

    Full Text Available Background. Several clinical techniques and a variety of biomaterials have been introduced over the years in an effort to overcome bone remodeling and resorption after tooth extraction. However, the predictability of these procedures in sockets with severely resorbed buccal/lingual plate due to periodontal disease is still unknown. Case Description. A patient with advanced periodontitis underwent extraction of upper right lateral and central incisors. The central incisor exhibited complete buccal bone plate loss and a 9 mm vertical bone deficiency on its palatal side. The alveolar sockets were filled with collagen sponge and covered with a nonresorbable high-density PTFE membrane. Primary closure was not attained and any rigid scaffold material was not used. Histologic analysis provided evidence of new bone formation. At 12 months a cone-beam computed tomographic scan revealed enough bone volume to insert two conventional dental implants in conjunction with minor horizontal bone augmentation procedures. Clinical Implications. This case report would seem to support the potential of the proposed reconstructive approach in changing the morphology of severely resorbed alveolar sockets, minimizing the need for advanced bone regeneration procedures during implant placement.

  6. BONE TUMOR ENVIRONMENT AS POTENTIAL THERAPEUTIC TARGET IN EWING SARCOMA

    Directory of Open Access Journals (Sweden)

    Françoise eREDINI

    2015-12-01

    Full Text Available Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, ES is an aggressive, rapidly fatal malignancy that mainly develops in osseous sites (85%, but also in extraskeletal soft tissue. It spreads naturally to the lungs, bones and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption is responsible for the clinical features of bone tumors including pain, vertebral collapse and spinal cord compression. Based on the vicious cycle concept of tumor cells and bone resorbing cells, drugs which target osteoclasts may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable niche for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing Sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates (BPs or drugs blocking the pro-resorbing cytokine Receptor Activator of NF-kappa B Ligand (RANKL. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

  7. Vertical distraction of the severely resorbed edentulous mandible : An assessment of treatment outcome

    NARCIS (Netherlands)

    Raghoebar, Gerry M.; Stellingsma, Kees; Meijer, Henny J. A.; Vissink, Arjan

    2008-01-01

    Purpose: To assess the treatment outcome (implant survival, surgical complications, patient satisfaction) of vertical distraction of the severely resorbed edentulous mandible. Materials and Methods: Forty-six patients with severe resorption of the edentulous mandible (bone height 5 to 8 mm, median 6

  8. Recombinant VSV G proteins reveal a novel raft-dependent endocytic pathway in resorbing osteoclasts

    International Nuclear Information System (INIS)

    Mulari, Mika T.K.; Nars, Martin; Laitala-Leinonen, Tiina; Kaisto, Tuula; Metsikkoe, Kalervo; Sun Yi; Vaeaenaenen, H. Kalervo

    2008-01-01

    Transcytotic membrane flow delivers degraded bone fragments from the ruffled border to the functional secretory domain, FSD, in bone resorbing osteoclasts. Here we show that there is also a FSD-to-ruffled border trafficking pathway that compensates for the membrane loss during the matrix uptake process and that rafts are essential for this ruffled border-targeted endosomal pathway. Replacing the cytoplasmic tail of the vesicular stomatitis virus G protein with that of CD4 resulted in partial insolubility in Triton X-100 and retargeting from the peripheral non-bone facing plasma membrane to the FSD. Recombinant G proteins were subsequently endosytosed and delivered from the FSD to the peripheral fusion zone of the ruffled border, which were both rich in lipid rafts as suggested by viral protein transport analysis and visualizing the rafts with fluorescent recombinant cholera toxin. Cholesterol depletion by methyl-β-cyclodextrin impaired the ruffled border-targeted vesicle trafficking pathway and inhibited bone resorption dose-dependently as quantified by measuring the CTX and TRACP 5b secreted to the culture medium and by measuring the resorbed area visualized with a bi-phasic labeling method using sulpho-NHS-biotin and WGA-lectin. Thus, rafts are vital for membrane recycling from the FSD to the late endosomal/lysosomal ruffled border and bone resorption

  9. Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma.

    Science.gov (United States)

    Redini, Françoise; Heymann, Dominique

    2015-01-01

    Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the "vicious cycle" concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable "niche" for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

  10. Fisetin antagonizes cell fusion, cytoskeletal organization and bone resorption in RANKL-differentiated murine macrophages.

    Science.gov (United States)

    Kim, Yun-Ho; Kim, Jung-Lye; Lee, Eun-Jung; Park, Sin-Hye; Han, Seon-Young; Kang, Soon Ah; Kang, Young-Hee

    2014-03-01

    Osteoclastogenesis is comprised of several stage s including progenitor survival, differentiation to mononuclear preosteoclasts, cell fusion to multinuclear mature osteoclasts, and activation to osteoclasts with bone resorbing activity. Botanical antioxidants are now being increasingly investigated for their health-promoting effects on bone. This study investigated that fisetin, a flavonol found naturally in many fruits and vegetables, suppressed osteoclastogenesis by disturbing receptor activator of nuclear factor (NF)-κB ligand (RANKL)-mediated signaling pathway and demoting osteoclastogenic protein induction. Nontoxic fisetin at ≤10 μM inhibited the induction of RANK, tumor necrosis factor receptor associated factor 6 (TRAF6) and the activation of NF-κB in RANKL-stimulated RAW 264.7 macrophages. In RANKL-differentiated osteoclasts cell fusion protein of E-cadherin was induced, which was dampened by fisetin. The formation of tartrate-resistance acid phosphatase-positive multinucleated osteoclasts was suppressed by adding fisetin to RANKL-exposed macrophages. It was also found that fisetin reduced actin ring formation and gelsolin induction of osteclasts enhanced by RANKL through disturbing c-Src-proline-rich tyrosine kinase 2 signaling. Fisetin deterred preosteoclasts from the cell-cell fusion and the organization of the cytoskeleton to seal the resorbing area and to secret protons for bone resorption. Consistently, the 5 day-treatment of fisetin diminished RANKL-induced cellular expression of carbonic anhydrase II and integrin β3 concurrently with a reduction of osteoclast bone-resorbing activity. Therefore, fisetin was a natural therapeutic agent retarding osteoclast fusion and cytoskeletal organization such as actin rings and ruffled boarder, which is a property of mature osteoclasts and is required for osteoclasts to resorb bone. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. A supra-cellular model for coupling of bone resorption to formation during remodeling

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L

    2014-01-01

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the ost......The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released...... by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow...... and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors...

  12. Delivery of gentamicin from resorbable polymeric carriers as anti-infective strategy for implant-associated osteomyelitis

    NARCIS (Netherlands)

    ter Boo, G.A.

    2016-01-01

    This thesis describes the development of gentamicin loaded resorbable polymeric carriers as anti-infective strategy for implant-associated osteomyelitis and their in vitro and in vivo evaluation. Local delivery of antibiotics has several advantages in the case of trauma to the bone and surrounding

  13. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

    Henriksen, K; Leeming, Diana Julie; Byrjalsen, I

    2007-01-01

    We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling...... of aged bones....

  14. Distinctive subdomains in the resorbing surface of osteoclasts.

    Directory of Open Access Journals (Sweden)

    Kinga A Szewczyk

    Full Text Available We employed a novel technique to inspect the substrate-apposed surface of activated osteoclasts, the cells that resorb bone, in the scanning electron microscope. The surface revealed unexpected complexity. At the periphery of the cells were circles and crescents of individual or confluent nodules. These corresponded to the podosomes and actin rings that form a 'sealing zone', encircling the resorptive hemivacuole into which protons and enzymes are secreted. Inside these rings and crescents the osteoclast surface was covered with strips and patches of membrane folds, which were flattened against the substrate surface and surrounded by fold-free membrane in which many orifices could be seen. Corresponding regions of folded and fold-free membrane were found by transmission electron microscopy in osteoclasts incubated on bone. We correlated these patterns with the distribution of several proteins crucial to resorption. The strips and patches of membrane folds corresponded in distribution to vacuolar H+-ATPase, and frequently co-localized with F-actin. Cathepsin K localized to F-actin-free foci towards the center of cells with circular actin rings, and at the retreating pole of cells with actin crescents. The chloride/proton antiporter ClC-7 formed a sharply-defined band immediately inside the actin ring, peripheral to vacuolar H+-ATPase. The sealing zone of osteoclasts is permeable to molecules with molecular mass up to 10,000. Therefore, ClC-7 might be distributed at the periphery of the resorptive hemivacuole in order to prevent protons from escaping laterally from the hemivacuole into the sealing zone, where they would dissolve the bone mineral. Since the activation of resorption is attributable to recognition of the αVβ3 ligands bound to bone mineral, such leakage would, by dissolving bone mineral, release the ligands and so terminate resorption. Therefore, ClC-7 might serve not only to provide the counter-ions that enable proton pumping, but

  15. DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Mahmood, Amer

    2011-01-01

    . In a number of in vitro culture systems, Dlk1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of proinflammatory bone-resorbing cytokines (eg, Il7, Tnfa, and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of Dlk1...... in the bone marrow by activated T cells. Interestingly, Dlk1(-/-) mice were significantly protected from ovx-induced bone loss compared with wild-type mice. Thus we identified Dlk1 as a novel regulator of bone mass that functions to inhibit bone formation and to stimulate bone resorption. Increasing DLK1...... production by T cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss....

  16. Erk1 positively regulates osteoclast differentiation and bone resorptive activity.

    Directory of Open Access Journals (Sweden)

    Yongzheng He

    Full Text Available The extracellular signal-regulated kinases (ERK1 and 2 are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1(-/- bone marrow mononuclear cells (BMMNCs demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2(-/- BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

  17. The effect of osteotomy dimension on osseointegration to resorbable media-treated implants: a study in the sheep.

    Science.gov (United States)

    Galli, Silvia; Jimbo, Ryo; Tovar, Nick; Yoo, Daniel Y; Anchieta, Rodolfo B; Yamaguchi, Satoshi; Coelho, Paulo G

    2015-03-01

    The drilling technique and the surface characteristics are known to influence the healing times of oral implants. The influence of osteotomy dimension on osseointegration of microroughned implant surfaces treated with resorbable blasting media was tested in an in vivo model. Ninety-six implants (ø4.5 mm, 8 mm in length) with resorbable blasting media-treated surfaces were placed in the ileum of six sheep. The final osteotomy diameters were 4.6 mm (reamer), 4.1 mm (loose), 3.7 mm (medium), and 3.2 mm (tight). After three and six weeks of healing, the implants were biomechanically tested and histologically evaluated. Statistical analysis was performed using Page L trend test for ordered and paired sample and linear regression, with significance level at p bone with all the implant surfaces and osteoblast lines were visible in all sections. The resorbable blasting media microroughed surfaces achieved successful osseointegration for all the instrumentation procedures tested, with higher osseointegration scores for the high insertion torque group. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. [Guided bone regeneration: general survey].

    Science.gov (United States)

    Cosyn, Jan; De Bruyn, Hugo

    2009-01-01

    The principle of 'guided bone regeneration' was first described in 1988 on the basis of animal-experimental data. Six weeks after transmandibular defects had been created and protected by non-resorbable teflonmembranes, complete bone regeneration was found. The technique was based on the selective repopulation of the wound: every infiltration of cells outside the neighbouring bone tissue was prevented by the application of the membrane. Additional animal experiments showed that guided bone regeneration was a viable treatment option for local bone defects surrounding dental implants. Clinical practice, however, showed that premature membrane exposure was a common complication, which was responsible for a tremendous reduction in regenerated bone volume. In addition, a second surgical intervention was always necessary to remove the membrane. As a result, resorbable alternatives were developed. Since these are less rigid, bone fillers are usually used simultaneously. These comprise autogenous bone chips and bone substitutes from allogenic or xenogenic origine. Also alloplastic materials could be used for this purpose. Based on their characteristics this article provides an overview of the biomaterials that could be considered for guided bone regeneration. Specific attention goes to their application in clinical practice.

  19. Polymeric membranes for guided bone regeneration.

    Science.gov (United States)

    Gentile, Piergiorgio; Chiono, Valeria; Tonda-Turo, Chiara; Ferreira, Ana M; Ciardelli, Gianluca

    2011-10-01

    In this review, different barrier membranes for guided bone regeneration (GBR) are described as a useful surgical technique to enhance bone regeneration in damaged alveolar sites before performing implants and fitting other dental appliances. The GBR procedure encourages bone regeneration through cellular exclusion and avoids the invasion of epithelial and connective tissues that grow at the defective site instead of bone tissue. The barrier membrane should satisfy various properties, such as biocompatibility, non-immunogenicity, non-toxicity, and a degradation rate that is long enough to permit mechanical support during bone formation. Other characteristics such as tissue integration, nutrient transfer, space maintenance and manageability are also of interest. In this review, various non-resorbable and resorbable commercially available membranes are described, based on expanded polytetrafluoroethylene, poly(lactic acid), poly(glycolic acid) and their copolymers. The polyester-based membranes are biodegradable, permit a single-stage procedure, and have higher manageability than non-resorbable membranes; however, they have shown poor biocompatibility. In contrast, membranes based on natural materials, such as collagen, are biocompatible but are characterized by poor mechanical properties and stability due to their early degradation. Moreover, new approaches are described, such as the use of multi-layered, graft-copolymer-based and composite membranes containing osteoconductive ceramic fillers as alternatives to conventional membranes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro

    DEFF Research Database (Denmark)

    Feng, Shan; Madsen, Suzi H; Viller, Natasja N

    2015-01-01

    Osteoclasts reside on bone and are the main bone resorbing cells playing an important role in bone homeostasis, while natural killer (NK) cells are bone-marrow-derived cells known to play a crucial role in immune defence against viral infections. Although mature NK cells traffic through bone marrow...

  1. Acceleration of Alveolar Ridge Augmentation Using a Low Dose of Recombinant Human Bone Morphogenetic Protein-2 Loaded on a Resorbable Bioactive Ceramic.

    Science.gov (United States)

    Fahmy, Rania A; Mahmoud, Naguiba; Soliman, Samia; Nouh, Samir R; Cunningham, Larry; El-Ghannam, Ahmed

    2015-12-01

    The aim of the present study was to evaluate the effect of a porous silica-calcium phosphate composite (SCPC50) loaded with and without recombinant human bone morphogenetic protein-2 (rhBMP-2) on alveolar ridge augmentation in saddle-type defects. Micro-granules of SCPC50 resorbable bioactive ceramic were coated with rhBMP-2 10 mg and then implanted into a saddle-type defect (12 × 7 mm) in a dog mandible and covered with a collagen membrane. Control groups included defects grafted with SCPC50 granules without rhBMP-2 and un-grafted defects. Bone healing was evaluated at 8 and 16 weeks using histologic and histomorphometric techniques. The increase in bone height and total defect fill were assessed for each specimen using the ImageJ 1.46 program. The release kinetics of rhBMP-2 was determined in vitro. The height of the bone in the grafted defects and the total defect fill were statistically analyzed. SCPC50 enhanced alveolar ridge augmentation as indicated by the increased vertical bone height, bone surface area, and bone volume after 16 weeks. SCPC50-rhBMP-2 provided a sustained release profile of a low effective dose (BMP-2 4.6 ± 1.34 pg/mL per hour) during the 1- to 21-day period. The slow rate of release of rhBMP-2 from SCPC50 accelerated synchronized complete bone regeneration and graft material resorption in 8 weeks. Successful rapid reconstruction of the alveolar ridge by SCPC50 and SCPC50-rhBMP-2 occurred without any adverse excessive bone formation, inflammation, or fluid-filled voids. Results of this study suggest that SCPC50 is an effective graft material to preserve the alveolar ridge after tooth extraction. Coating SCPC50-rhBMP-2 further accelerated bone regeneration and a considerable increase in vertical bone height. These findings make SCPC50 the primary choice as a carrier for rhBMP-2. SCPC50-rhBMP-2 can serve as an alternative to autologous bone grafting. Published by Elsevier Inc.

  2. Bone remodelling: its local regulation and the emergence of bone fragility.

    Science.gov (United States)

    Martin, T John; Seeman, Ego

    2008-10-01

    Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.

  3. A novel one-pot process for near-net-shape fabrication of open-porous resorbable hydroxyapatite/protein composites and in vivo assessment

    International Nuclear Information System (INIS)

    Mueller, Berit; Koch, Dietmar; Lutz, Rainer; Schlegel, Karl A.; Treccani, Laura; Rezwan, Kurosch

    2014-01-01

    We present a mild one-pot freeze gelation process for fabricating near-net, complex-shaped hydroxyapatite scaffolds and to directly incorporate active proteins during scaffold processing. In particular, the direct protein incorporation enables a simultaneous adjustment and control of scaffold microstructure, porosity, resorbability and enhancement of initial mechanical and handling stability. Two proteins, serum albumin and lysozyme, are selected and their effect on scaffold stability and microstructure investigated by biaxial strength tests, electron microscopy, and mercury intrusion porosimetry. The resulting hydroxyapatite/protein composites feature adjustable porosities from 50% to 70% and a mechanical strength ranging from 2 to 6 MPa comparable to that of human spongiosa without any sintering step. Scaffold degradation behaviour and protein release are assessed by in vitro studies. A preliminary in vivo assessment of scaffold biocompatibility and resorption behaviour in adult domestic pigs is discussed. After implantation, composites were resorbed up to 50% after only 4 weeks and up to 65% after 8 weeks. In addition, 14% new bone formation after 4 weeks and 37% after 8 weeks were detected. All these investigations demonstrate the outstanding suitability of the one-pot-process to create, in a customisable and reliable way, biocompatible scaffolds with sufficient mechanical strength for handling and surgical insertion, and for potential use as biodegradable bone substitutes and versatile platform for local drug delivery. - Highlights: • We present a one-pot process for directly incorporating protein into HAp scaffolds. • The effect of two model proteins, BSA and LSZ, on scaffold properties is analysed. • HAp/protein scaffolds feature a mechanical strength comparable to human spongiosa. • BSA incorporation in scaffolds leads to strength increase despite porosity increment. • New bone formation in-vivo exceeds established xenograft bone substitutes

  4. Three-Dimensional Volumetric Changes in Severely Resorbed Alveolar Sockets After Ridge Augmentation with Bovine-Derived Xenograft and Resorbable Barrier: A Preliminary Study on CBCT Imaging.

    Science.gov (United States)

    Manavella, Valeria; Romano, Federica; Corano, Lisa; Bignardi, Cristina; Aimetti, Mario

    The primary aim of the study was to describe a novel technique to evaluate volumetric hard tissue dimensional changes after ridge augmentation procedures. The secondary aim was to apply this newly developed measuring method to compromised alveolar sockets grafted with a slowly resorbing biomaterial covered with a collagen membrane. Eleven patients (6 men and 5 women, mean age 52.7 ± 8.3 years) requiring extraction of one hopeless tooth for severe periodontitis in the maxillary anterior area were consecutively treated with a ridge augmentation procedure. All experimental sockets showed advanced buccal bone plate deficiency and were grafted with deproteinized bovine bone mineral with 10% collagen covered with a collagen membrane. Sockets healed by secondary intention. Three-dimensional volumetric alveolar bone changes were calculated by superimposing cone beam computed tomography scans obtained before and 12 months after the augmentation procedure. After 12 months, the alveolar mineralized tissue filled 91.20% ± 7.96% of the maximum volume for regeneration. The augmentation procedure appeared not only to compensate for bone remodeling in most alveolar regions but also to repair a significant portion of the buccal wall. The most significant ridge width changes occurred 1 mm apical to the bone crest (2.33 ± 1.46 mm, P socket volume. A ridge preservation technique performed with collagenated bovine bone and a collagen membrane was able to improve ridge shape and dimensions in compromised alveolar sockets.

  5. Bone scan and SPECT/CT findings in marble bone disease

    International Nuclear Information System (INIS)

    Kapoor, Jiten; Joshi, Prathamesh; Lele, Vikram

    2012-01-01

    Marble bone disease or osteopetrosis, is a rare inborn disorder characterized by the failure of osteoclasts to resorb bone. Overall incidence of the disease is estimated to be 1 case in 100,000-500,000 population. Whereas the radiographic features of the disease are well known, information on bone scan imaging is sparse in the literature. We present technitium 99m methylene diphosphonate ( 99m Tc MDP) bone scan features of osteopetrosis, along with single photon emission computed tomography-computed tomography(SPECT/CT) correlation in a young male.

  6. Bone scan and SPECT/CT findings in marble bone disease

    Energy Technology Data Exchange (ETDEWEB)

    Kapoor, Jiten; Joshi, Prathamesh; Lele, Vikram [Jaslok Hospital and Research Centre, Woril (India)

    2012-03-15

    Marble bone disease or osteopetrosis, is a rare inborn disorder characterized by the failure of osteoclasts to resorb bone. Overall incidence of the disease is estimated to be 1 case in 100,000-500,000 population. Whereas the radiographic features of the disease are well known, information on bone scan imaging is sparse in the literature. We present technitium 99m methylene diphosphonate ({sup 99m}Tc MDP) bone scan features of osteopetrosis, along with single photon emission computed tomography-computed tomography(SPECT/CT) correlation in a young male.

  7. In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes

    International Nuclear Information System (INIS)

    Burger, E.H.; Van der Meer, J.W.; van de Gevel, J.S.; Gribnau, J.C.; Thesingh, G.W.; van Furth, R.

    1982-01-01

    The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45 Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes

  8. Interleukin-2 stimulates osteoclastic activity: Increased acid production and radioactive calcium release

    International Nuclear Information System (INIS)

    Ries, W.L.; Seeds, M.C.; Key, L.L.

    1989-01-01

    Recombinant human interleukin-2 (IL-2) was studied to determine effects on acid production by individual osteoclasts in situ on mouse calvarial bones. This analysis was performed using a microspectrofluorimetric technique to quantify acid production in individual cells. Radioactive calcium release was determined using calvarial bones in a standard tissue culture system. This allowed us to correlate changes in acid production with a measure of bone resorption. IL-2 stimulated acid production and bone resorbing activity. Both effects were inhibited by calcitonin. No stimulation of bone resorption occurred when IL-2-containing test media was incubated with a specific anti-IL-2 antibody and ultrafiltered. Our data demonstrated a correlation between acid production and bone resorbing activity in mouse calvaria exposed to parathyroid hormone (PTH). The data obtained from cultured mouse calvaria exposed to IL-2 demonstrated similar stimulatory effects to those seen during PTH exposure. These data suggest that calvaria exposed to IL-2 in vitro have increased osteoclastic acid production corresponding with increased bone resorption. (author)

  9. Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo.

    Science.gov (United States)

    Tower, R J; Campbell, G M; Müller, M; Glüer, C C; Tiwari, S

    2015-05-01

    The turnover of bone is a tightly regulated process between bone formation and resorption to ensure skeletal homeostasis. This process differs between bone types, with trabecular bone often associated with higher turnover than cortical bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in structure and mineral content, but are limited in the study of metabolic activity at a single time point, while analyses of serum markers can reveal changes in bone metabolism, but cannot delineate the origin of any aberrant findings. To obtain a site-specific assessment of bone metabolic status, bisphosphonate binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Using time-lapse micro-CT, longitudinal bone turnover was quantified. The spine showed a significantly greater percent resorbing volume and surface in response to OVX, while mice treated with PTH showed significantly greater resorbing volume per bone surface in the spine and significantly greater forming surfaces in the knee. Correlation studies between binding kinetics and micro-CT suggest that forming surfaces, as assessed by time-lapse micro-CT, are preferentially reflected in the rate constant values while forming and resorbing bone volumes primarily affect plateau values. Additionally, we developed a blood pool correction method which now allows for quantitative multi-compartment analyses to be conducted using FMT. These results further expand our understanding of bisphosphonate binding and the use of bisphosphonate binding kinetics as a tool to monitor site-specific changes in bone metabolism in

  10. Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

    International Nuclear Information System (INIS)

    Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

    2011-01-01

    During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered) ). Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research highlights: → 3-Day imatinib treatment. → Causes growth plate anomalies in young rats. → Causes biomechanical changes and significant bone loss at distal trabecular bone. → Results in loss of osteoclasts at osteochondral junction.

  11. Arctigenin suppresses receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow-derived macrophages.

    Science.gov (United States)

    Kim, A-Ram; Kim, Hyuk Soon; Lee, Jeong Min; Choi, Jung Ho; Kim, Se Na; Kim, Do Kyun; Kim, Ji Hyung; Mun, Se Hwan; Kim, Jie Wan; Jeon, Hyun Soo; Kim, Young Mi; Choi, Wahn Soo

    2012-05-05

    Osteoclasts, multinucleated bone-resorbing cells, are closely associated with bone diseases such as rheumatoid arthritis and osteoporosis. Osteoclasts are derived from hematopoietic precursor cells, and their differentiation is mediated by two cytokines, including macrophage colony stimulating factor and receptor activator of nuclear factor κB ligand (RANKL). Previous studies have shown that arctigenin exhibits an anti-inflammatory effect. However, the effect of arctigenin on osteoclast differentiation is yet to be elucidated. In this study, we found that arctigenin inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages in a dose-dependent manner and suppressed RANKL-mediated bone resorption. Additionally, the expression of typical marker proteins, such as NFATc1, c-Fos, TRAF6, c-Src, and cathepsin K, were significantly inhibited. Arctigenin inhibited the phosphorylation of Erk1/2, but not p38 and JNK, in a dose-dependent manner. Arctigenin also dramatically suppressed immunoreceptor tyrosine-based activation motif-mediated costimulatory signaling molecules, including Syk and PLCγ2, and Gab2. Notably, arctigenin inhibited the activation of Syk through RANKL stimulation. Furthermore, arctigenin prevented osteoclast differentiation in the calvarial bone of mice following stimulation with lipopolysaccharide. Our results show that arctigenin inhibits osteoclast differentiation in vitro and in vivo. Therefore, arctigenin may be useful for treating rheumatoid arthritis and osteoporosis. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Midlife women, bone health, vegetables, herbs and fruit study. The Scarborough Fair study protocol

    Directory of Open Access Journals (Sweden)

    Gunn Caroline A

    2013-01-01

    Full Text Available Abstract Background Bone loss is accelerated in middle aged women but increased fruit/vegetable intake positively affects bone health by provision of micronutrients essential for bone formation, buffer precursors which reduce acid load and phytochemicals affecting inflammation and oxidative stress. Animal studies demonstrated bone resorption inhibiting properties of specific vegetables, fruit and herbs a decade ago. Objective: To increase fruit/vegetable intake in post menopausal women to 9 servings/day using a food specific approach to significantly reduce dietary acid load and include specific vegetables, fruit and herbs with bone resorbing inhibiting properties to assess effect on bone turnover, metabolic and inflammatory markers. Methods/Design The Scarborough Fair Study is a randomised active comparator controlled multi centre trial. It aimed to increase fruit and vegetable intake in 100 post menopausal women from ≤ 5 servings/day to ≥ 9 servings/day for 3 months. The women in the dietary intervention were randomly assigned to one of the two arms of the study. Both groups consumed ≥ 9 servings/day of fruit/vegetables and selected herbs but the diet of each group emphasised different fruit/vegetables/herbs with one group (B selecting from a range of vegetables, fruit and culinary herbs with bone resorbing inhibiting properties. 50 women formed a negative control group (Group C usual diet. Primary outcome variables were plasma bone markers assessed at baseline, 6 weeks and 12 weeks. Secondary outcome variables were plasma inflammation and metabolic markers and urinary electrolytes (calcium, magnesium, potassium and sodium assessed at baseline and 12 weeks. Dietary intake and urine pH change also were outcome variables. The dietary change was calculated with 3 day diet diaries and a 24 hour recall. Intervention participants kept a twice weekly record of fruit, vegetable and herb intake and urine pH. Discussion This study will provide

  13. Stem cell factor stimulates chicken osteoclast activity in vitro

    NARCIS (Netherlands)

    van't Hof, R. J.; von Lindern, M.; Nijweide, P. J.; Beug, H.

    1997-01-01

    Stem cell factor (SCF) is a polypeptide growth factor active on multiple cell types, mainly of hematopoietic origin. We studied the effects of avian SCF on the differentiation of chicken osteoclasts from their putative progenitors as well as on the bone-resorbing activity of terminally

  14. Benefits of mineralized bone cortical allograft for immediate implant placement in extraction sites: an in vivo study in dogs.

    Science.gov (United States)

    Orti, Valérie; Bousquet, Philippe; Tramini, Paul; Gaitan, Cesar; Mertens, Brenda; Cuisinier, Frédéric

    2016-10-01

    The aim of the present study was to evaluate the effectiveness of using a mineralized bone cortical allograft (MBCA), with or without a resorbable collagenous membrane derived from bovine pericardium, on alveolar bone remodeling after immediate implant placement in a dog model. Six mongrel dogs were included. The test and control sites were randomly selected. Four biradicular premolars were extracted from the mandible. In control sites, implants without an allograft or membrane were placed immediately in the fresh extraction sockets. In the test sites, an MBCA was placed to fill the gap between the bone socket wall and implant, with or without a resorbable collagenous membrane. Specimens were collected after 1 and 3 months. The amount of residual particles and new bone quality were evaluated by histomorphometry. Few residual graft particles were observed to be closely embedded in the new bone without any contact with the implant surface. The allograft combined with a resorbable collagen membrane limited the resorption of the buccal wall in height and width. The histological quality of the new bone was equivalent to that of the original bone. The MBCA improved the quality of new bone formation, with few residual particles observed at 3 months. The preliminary results of this animal study indicate a real benefit in obtaining new bone as well as in enhancing osseointegration due to the high resorbability of cortical allograft particles, in comparison to the results of xenografts or other biomaterials (mineralized or demineralized cancellous allografts) that have been presented in the literature. Furthermore, the use of an MBCA combined with a collagen membrane in extraction and immediate implant placement limited the extent of post-extraction resorption.

  15. RANK, RANKL and osteoprotegerin in arthritic bone loss

    Directory of Open Access Journals (Sweden)

    M.C. Bezerra

    2005-02-01

    Full Text Available Rheumatoid arthritis is characterized by the presence of inflammatory synovitis and destruction of joint cartilage and bone. Tissue proteinases released by synovia, chondrocytes and pannus can cause cartilage destruction and cytokine-activated osteoclasts have been implicated in bone erosions. Rheumatoid arthritis synovial tissues produce a variety of cytokines and growth factors that induce monocyte differentiation to osteoclasts and their proliferation, activation and longer survival in tissues. More recently, a major role in bone erosion has been attributed to the receptor activator of nuclear factor kappa B ligand (RANKL released by activated lymphocytes and osteoblasts. In fact, osteoclasts are markedly activated after RANKL binding to the cognate RANK expressed on the surface of these cells. RANKL expression can be upregulated by bone-resorbing factors such as glucocorticoids, vitamin D3, interleukin 1 (IL-1, IL-6, IL-11, IL-17, tumor necrosis factor-alpha, prostaglandin E2, or parathyroid hormone-related peptide. Supporting this idea, inhibition of RANKL by osteoprotegerin, a natural soluble RANKL receptor, prevents bone loss in experimental models. Tumor growth factor-ß released from bone during active bone resorption has been suggested as one feedback mechanism for upregulating osteoprotegerin and estrogen can increase its production on osteoblasts. Modulation of these systems provides the opportunity to inhibit bone loss and deformity in chronic arthritis.

  16. Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption.

    Science.gov (United States)

    van't Hof, R J; Armour, K J; Smith, L M; Armour, K E; Wei, X Q; Liew, F Y; Ralston, S H

    2000-07-05

    Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study, we investigated the role that the iNOS pathway plays in mediating the bone-resorbing effects of IL-1 by studying mice with targeted disruption of the iNOS gene. Studies in vitro and in vivo showed that iNOS-deficient mice exhibited profound defects of IL-1-induced osteoclastic bone resorption but responded normally to calciotropic hormones such as 1,25 dihydroxyvitamin D3 and parathyroid hormone. Immunohistochemical studies and electrophoretic mobility shift assays performed on bone marrow cocultures from iNOS-deficient mice showed abnormalities in IL-1-induced nuclear translocation of the p65 component of NFkappaB and in NFkappaB-DNA binding, which were reversed by treatment with the NO donor S-nitroso-acetyl penicillamine. These results show that the iNOS pathway is essential for IL-1-induced bone resorption and suggest that the effects of NO may be mediated by modulating IL-1-induced nuclear activation of NFkappaB in osteoclast precursors.

  17. Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption

    Science.gov (United States)

    van't Hof, R. J.; Armour, K. J.; Smith, L. M.; Armour, K. E.; Wei, X. Q.; Liew, F. Y.; Ralston, S. H.

    2000-01-01

    Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study, we investigated the role that the iNOS pathway plays in mediating the bone-resorbing effects of IL-1 by studying mice with targeted disruption of the iNOS gene. Studies in vitro and in vivo showed that iNOS-deficient mice exhibited profound defects of IL-1-induced osteoclastic bone resorption but responded normally to calciotropic hormones such as 1,25 dihydroxyvitamin D3 and parathyroid hormone. Immunohistochemical studies and electrophoretic mobility shift assays performed on bone marrow cocultures from iNOS-deficient mice showed abnormalities in IL-1-induced nuclear translocation of the p65 component of NFκB and in NFκB-DNA binding, which were reversed by treatment with the NO donor S-nitroso-acetyl penicillamine. These results show that the iNOS pathway is essential for IL-1-induced bone resorption and suggest that the effects of NO may be mediated by modulating IL-1-induced nuclear activation of NFκB in osteoclast precursors. PMID:10869429

  18. Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo.

    Science.gov (United States)

    Baek, Jong Min; Kim, Ju-Young; Ahn, Sung-Jun; Cheon, Yoon-Hee; Yang, Miyoung; Oh, Jaemin; Choi, Min Kyu

    2016-03-01

    Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (μ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis.

  19. Sinus lift using a nanocrystalline hydroxyapatite silica gel in severely resorbed maxillae: histological preliminary study.

    Science.gov (United States)

    Canullo, Luigi; Dellavia, Claudia

    2009-10-01

    The aim of this preliminary study was to evaluate histologically a nanocrystalline hydroxyapatite silica gel in maxillary sinus floor grafting in severely resorbed maxillae. A total of 16 consecutive patients scheduled for sinus lift were recruited during this study. Patients were randomly divided in two groups, eight patients each. In both groups, preoperative residual bone level ranged between 1 and 3 mm (mean value of 2.03 mm). No membrane was used to occlude the buccal window. Second surgery was carried out after a healing period of 3 months in Group 1 and 6 months in Group 2. Using a trephine bur, one bone specimen was harvested from each augmented sinus and underwent histological and histomorphometric analysis. Histological analysis showed significant new bone formation and remodeling of the grafted material. In the cores obtained at 6 months, regenerated bone, residual NanoBone, and bone marrow occupied respectively 48 +/- 4.63%, 28 +/- 5.33%, and 24 +/- 7.23% of the grafted volume. In the specimens taken 3 months after grafting, mean new bone was 8 +/- 3.34%, mean NanoBone was 45 +/- 5.10%, and mean bone marrow was 47 +/- 6.81% of the bioptical volume. Within the limits of this preliminary prospective study, it was concluded that grafting of maxillary sinus using nanostructured hydroxyapatite silica gel as only bone filler is a reliable procedure also in critical anatomic conditions and after early healing period.

  20. Uranium in bone: metabolic and autoradiographic studies in the rat

    International Nuclear Information System (INIS)

    Priest, N.D.; Haines, J.W.; Howells, G.R.; Green, D.

    1982-01-01

    The distribution and retention of intravenously injected hexavalent uranium-233 in the skeleton of the female rat has been investigated using a variety of autoradiographic and radiochemical techniques. These showed that approximately one third of the injected uranium is deposited in the skeleton where it is retained with an initial biological half-time of approximately 40 days. The studies also showed that: 1) Uranium is initially deposited on to all types of bone surface, but preferentially on to those that are accreting. 2) Uranium is deposited in the calcifying zones of skeletal cartilage. 3) Bone accretion results in the burial of surface deposits of uranium. 4) Bone resorption causes the removal of uranium from surfaces. 5) Resorbed uranium is not retained by osteoclasts and macrophages in the bone marrow. 6) Uranium removed from bone surfaces enters the bloodstream where most is either redeposited in bone or excreted via the kidneys. 7) The recycling of resorbed uranium within the skeleton tends to produce a uniform level of uranium contamination throughout mineralized bone. These results are taken to indicate that uranium deposition in bone shares characteristics in common with both the 'volume-seeking radionuclides' typified by the alkaline earth elements and with the 'bone surface-seeking radionuclides' typified by plutonium. (author)

  1. Uranium in bone: metabolic and autoradiographic studies in the rat.

    Science.gov (United States)

    Priest, N D; Howells, G R; Green, D; Haines, J W

    1982-03-01

    The distribution and retention of intravenously injected hexavalent uranium-233 in the skeleton of the female rat has been investigated using a variety of autoradiographic and radiochemical techniques. These showed that approximately one third of the injected uranium is deposited in the skeleton where it is retained with an initial biological half-time of approximately 40 days. The studies also showed that: 1 Uranium is initially deposited onto all types of bone surface, but preferentially onto those that are accreting. 2 Uranium is deposited in the calcifying zones of skeletal cartilage. 3 Bone accretion results in the burial of surface deposits of uranium. 4 Bone resorption causes the removal of uranium from surfaces. 5 Resorbed uranium is not retained by osteoclasts and macrophages in the bone marrow. 6 Uranium removed from bone surfaces enters the bloodstream where most is either redeposited in bone or excreted via the kidneys. 7 The recycling of resorbed uranium within the skeleton tends to produce a uniform level of uranium contamination throughout mineralized bone. These results are taken to indicate that uranium deposition in bone shares characteristics in common with both the 'volume-seeking radionuclides' typified by the alkaline earth elements and with the 'bone surface-seeking radionuclides' typified by plutonium.

  2. Water extract of Acer tegmentosum reduces bone destruction by inhibiting osteoclast differentiation and function.

    Science.gov (United States)

    Ha, Hyunil; Shim, Ki-Shuk; Kim, Taesoo; An, Hyosun; Lee, Chung-Jo; Lee, Kwang Jin; Ma, Jin Yeul

    2014-04-01

    The stem of Acer tegmentosum has been widely used in Korea for the treatment of hepatic disorders. In this study, we investigated the bone protective effect of water extract of the stem of Acer tegmentosum (WEAT). We found that WEAT inhibits osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclast differentiation. In osteoclast precursor cells, WEAT inhibited RANKL-induced activation of JNK, NF-κB, and cAMP response element-binding protein, leading to suppression of the induction of c-Fos and nuclear factor of activated T cells cytoplasmic 1, key transcription factors for osteoclast differentiation. In addition, WEAT inhibited bone resorbing activity of mature osteoclasts. Furthermore, the oral administration of WEAT reduced RANKL-induced bone resorption and trabecular bone loss in mice. Taken together, our study demonstrates that WEAT possesses a protective effect on bone destruction by inhibiting osteoclast differentiation and function.

  3. Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

    Directory of Open Access Journals (Sweden)

    Patricia Ros-Tárraga

    2016-09-01

    Full Text Available This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared. The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung as a result of degradation products being released.

  4. Tooth apatite as a bone substitute: an experimental study and clinical applications

    International Nuclear Information System (INIS)

    Eun-Seok Kim; Pill-Hoon Choung

    1999-01-01

    The purpose of this study is to evaluate the usefulness of calcined teeth powder as biological apatite. The animal experiment was performed in 36 rabbits aging 6 weeks and weighing 1.6 kg. In experimental group, tooth apatite powder was implanted to 10 mm bony defects in diameter made on the cranial bone of the rabbits. As control groups, synthetic porous hydroxyapatite and resorbable type calcium carbonate were implanted to the defects of same size. Each group was sacrificed in 1, 2, 4, 6, 8, 12 weeks after the surgery. Specimens were prepared for decalcified samples and observed by a light microscope. And we also performed quantitative analysis of new bone formation through image analysis using computer. In clinical applications, we used tooth apatite alone or mixed with decalcified freeze-dried bone for reconstruction of bony defects in 15 patients undergone enucleation of cyst or ameloblastoma. The obtained results were as follows; 1) The powder of the calcined teeth was called as 'tooth apatite' and it seemed to have biocompatibility in rabbits and human. 2) In group of tooth apatite, after 4 weeks of operation, new bone directly bonded to the particles was observed. And in 12 weeks of it, new bone occupied most of the bony defects. In 6 weeks, resorption of the tooth apatite particles was observed. Thus the tooth apatite was regarded as one of resorbable apatite. 3) The group of tooth apatite showed new bone formation similar to the group of porous hydroxyapatite, but they were inferior to the group of resorbable calcium carbonate. 4) In clinical application, tooth apatite had biocompatibility and new bone formation was observed without any complication except for 1 case. So we think it is a useful bone substitute with osteoconductivity

  5. Similar healthy osteoclast and osteoblast activity on nanocrystalline hydroxyapatite and nanoparticles of tri-calcium phosphate compared to natural bone

    Directory of Open Access Journals (Sweden)

    MacMillan AK

    2014-12-01

    Full Text Available Adam K MacMillan,1 Francis V Lamberti,1 Julia N Moulton,2 Benjamin M Geilich,2 Thomas J Webster2,3 1RTI Surgical, Alachua, FL, USA; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: While there have been numerous studies to determine osteoblast (bone forming cell functions on nanocrystalline compared to micron crystalline ceramics, there have been few studies which have examined osteoclast activity (including tartrate-resistant acid phosphatase, formation of resorption pits, size of resorption pits, and receptor activator of nuclear factor κB [RANK]. This is despite the fact that osteoclasts are an important part of maintaining healthy bone since they resorb bone during the bone remodeling process. Moreover, while it is now well documented that bone formation is enhanced on nanoceramics compared to micron ceramics, some have pondered whether osteoblast functions (such as osteoprotegerin and RANK ligand [RANKL] are normal (ie, non-diseased on such materials compared to natural bone. For these reasons, the objective of the present in vitro study was to determine various functions of osteoclasts and osteoblasts on nanocrystalline and micron crystalline hydroxyapatite as well as tri-calcium phosphate materials and compare such results to cortical and cancellous bone. Results showed for the first time similar osteoclast activity (including tartrate-resistant acid phosphatase, formation of resorption pits, size of resorption pits, and RANK and osteoblast activity (osteoprotegerin and RANKL on nanocrystalline hydroxyapatite compared to natural bone, whereas osteoclast and osteoblast functions on micron crystalline versions of these ceramics were much different than natural bone. In this manner, this study provides additional evidence that nanocrystalline calcium phosphates can serve as suitable synthetic

  6. Patients' preoperative expectations and postoperative satisfaction of dysgnathic patients operated on with resorbable osteosyntheses.

    Science.gov (United States)

    Ballon, Alexander; Laudemann, Katharina; Sader, Robert; Landes, Constantin A

    2011-03-01

    This study evaluated whether personal expectations and satisfaction throughout orthognathic surgery were fulfilled. In addition, patients were interrogated about their experience of resorbable osteosynthesis. A total of 50 patients were interviewed 3 times each throughout the study by a mixed questionnaire of standard psychologic tests and a tailored itemized questionnaire regarding their expectations regarding resorbable osteofixation and their postoperative satisfaction. A postoperative increase in self-esteem and approach to life were evident. An examination of Oral Health-Related Quality of Life showed constant quality of life; an examination of Oral Health Impact Profile-Germany) showed no postoperative difficulties in dental hygiene and nutrition. No statistically significant change in any of the tests could be expressly determined. Avoidance of secondary surgery motivated 94% to choose resorbable osteofixations, although a mere 66% had heard of them before; 90% of patients were satisfied with the operation result. Orthognathic surgery cannot change preexistent depression or a problematic social background. Mastication and oral health improved, and postoperative happiness and confidence increased. When given the choice between resorbable fixation and titanium osteofixation, patients generally preferred resorbable fixations.

  7. Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Sara Rocío Chuguransky

    2016-01-01

    Full Text Available Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs that impair bone marrow progenitor cell (BMPC osteogenic potential and decrease bone quality. Here we investigated the in vitro effect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats. We also evaluated the in vivo effect of alendronate (administered orally to rats with insulin-deficient Diabetes on long-bone microarchitecture and BMPC multilineage potential. In vitro, the osteogenesis (Runx2, alkaline phosphatase, type 1 collagen, and mineralization and chondrogenesis (glycosaminoglycan production of BMPC were both decreased by AGEs, while coincubation with alendronate prevented these effects. The adipogenesis of BMPC (PPARγ, intracellular triglycerides, and lipase was increased by AGEs, and this was prevented by coincubation with alendronate. In vivo, experimental Diabetes (a decreased femoral trabecular bone area, osteocyte density, and osteoclastic TRAP activity; (b increased bone marrow adiposity; and (c deregulated BMPC phenotypic potential (increasing adipogenesis and decreasing osteogenesis and chondrogenesis. Orally administered alendronate prevented all these Diabetes-induced effects on bone. Thus, alendronate could improve bone alterations in diabetic rats by preventing the antiosteogenic, antichondrogenic, and proadipocytic effects of AGEs on BMPC.

  8. Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice

    Directory of Open Access Journals (Sweden)

    Jong Min Baek

    2014-08-01

    Full Text Available Aconitum pseudo-laeve var. erectum (APE has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone resorption. In this study, we confirmed that the administration of APE could restore normal skeletal conditions in a murine model of lipopolysaccharide (LPS-induced bone loss via a decrease in the receptor activator of nuclear factor kappa-B ligand (RANKL/osteoprotegerin (OPG ratio and osteoclast number. We then investigated the effect of APE on the RANKL-induced formation and function of osteoclasts to elucidate its underlying molecular mechanisms. APE suppressed the formation of tartrate-resistant acid phosphatase (TRAP-positive cells, as well as the bone-resorbing activity of mature osteoclasts. Furthermore, APE attenuated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1 and c-Fos without affecting any early signal pathway of osteoclastogenesis. Subsequently, APE significantly downregulated the expression of various genes exclusively expressed in osteoclasts. These results demonstrate that APE restores LPS-induced bone loss through a decrease of the serum RANKL/OPG ratio, and inhibits osteoclast differentiation and function, suggesting the promise of APE as a potential cure for various osteoclast-associated bone diseases.

  9. Contemporary guided bone regeneration therapy for unaesthetic anterior peri-implantitis case

    Directory of Open Access Journals (Sweden)

    Benso Sulijaya

    2016-12-01

    Full Text Available Background: Dental implant is one of an alternative solutions reconstruction therapy for missing teeth. Complication of dental implant could occurs and leading to implant failure. In order to restore the complication, surgical treatment with guided bone regeneration (GBR is indicated. The potential use of bone substitutes is widely known to be able to regenerate the bone surrounding the implant and maintain bone volume. Purpose: The study aimed to demonstrate the effectiveness of implant-bone fully coverage by using sandwich technique of biphasic calcium phosphate (BCP and demineralized freeze-dried bone allografts (DFDBA bone substitutes combined with collagen resorbable membrane. Case: A 24-year-old male came with diagnosis of peri-implantitis on implant #11. Clinical finding indicated that implant thread was exposed on the labial aspect. Case management: After initial therapy including oral hygiene improvement performed, an operator did a contemporary GBR to correct the defect. Bone graft materials used were 40% β-tri calcium phosphate (β-TCP-60% hydroxyapatite (HA on the outer layer and DFDBA on the inner layer of the defect. Resorbable collagen membrane was used to cover the graft. Conclusion: GBR with sandwich technique could serve as one of the treatment choices for correcting an exposed anterior implant that would enhance the successful aesthetic outcome.

  10. The role of active ingredients nanopowder Stichopus hermanii gel to bone resorption in tension area of orthodontic tooth movement

    Directory of Open Access Journals (Sweden)

    Noengki Prameswari

    2017-12-01

    Full Text Available Background: Orthodontic tooth movement is a continual and balanced process between bone deposition and bone resorption in pressure and tension sites. Stichopus hermanii is one of the best fishery commodities in Indonesia. It is natural and contains various active ingredients such as hyaluronic acid, chondroitin sulphate, cell growth factor, eicosa pentaenoic acid (EPA docosa hexaenoic acid (DHA and flavonoid that potentially play a role in orthodontic tooth movement. Purpose: The aim of this study was to investigate the active ingredients of nanopowder Stichopus hermanii promoting bone resorption in tension area orthodontic tooth movement. Methods: A quantitative test for active ingredients of stichopus hermanii was conducted. Thirty two male Cavia cobaya were divisibled became four groups. K (– groups as a negative control group (without treatment, K (+ groups as a positive control group which were provided with a separator rubber for orthodontic tooth movement, and P1, P2 groups, which were treated with 3% and 3.5% stichopus hermanii for orthodontic tooth movement. After treatment the cavia cobaya were sacrificed. TRAP-6 expression as a osteoclast marker was examined by means of an immunohistochemistry method. Results: A one-way Anova test confirmed that TRAP-6 expression was significantly increased with p = 0.00 (p≤0,05 in P2 compared to K (+. P2 to K (–, P2 to P1 and P1 to K (+ had no significant differences Conclusion: Nanopowder Stichopus hermanii 3.5% has an active ingredient that could increase osteoclast activity to resorb periodontal ligament and alveolar bone in tension areas of orthodontic tooth movement.

  11. The cell biology and role of resorptive cells in diseases: A review.

    Science.gov (United States)

    Babaji, Prashant; Devanna, Raghu; Jagtap, Kiran; Chaurasia, Vishwajit Rampratap; Jerry, Jeethu John; Choudhury, Basanta Kumar; Duhan, Dinesh

    2017-01-01

    Resorptive cells are responsible for the resorption of mineralized matrix of hard tissues. Bone-resorbing cells are called osteoclasts; however, they can resorb mineralized dental tissues or calcified cartilage and then they are called odontoclasts and chondroclasts, respectively. Resorptive cells form when mononuclear precursors derived from a monocyte-macrophage cell lineage are attracted to certain mineralized surfaces and subsequently fuse and adhere onto them for exerting their resorbing activity. These cells are responsible for degradation of calcified extracellular matrix composed of organic molecules and hydroxyapatite. The activity of these cells can be observed in both physiological and pathological processes throughout life and their activity is mainly required in bone turnover and growth, spontaneous and induced (orthodontic) tooth movement, tooth eruption, and bone fracture healing, as well as in pathological conditions such as osteoporosis, osteoarthritis, and bone metastasis. In addition, they are responsible for daily control of calcium homeostasis. Clastic cells also resorb the primary teeth for shedding before the permanent teeth erupt into the oral cavity.

  12. Ridge Preservation Comparing a Nonresorbable PTFE Membrane to a Resorbable Collagen Membrane: A Clinical and Histologic Study in Humans.

    Science.gov (United States)

    Arbab, Hussain; Greenwell, Henry; Hill, Margaret; Morton, Dean; Vidal, Ricardo; Shumway, Brian; Allan, Nicholas D

    2016-02-01

    The primary aim of this randomized, controlled, blinded clinical trial was to compare the effect of a resorbable collagen membrane (CM group) versus a nonresorbable high-density polytetrafluoroethylene membrane (PTFE group) on the clinical and histologic outcomes of a ridge preservation procedure. All 24 sites received an intrasocket cancellous allograft and a buccal overlay bovine derived xenograft. The change in horizontal crestal ridge width was -1.4 ± 1.2 mm for the CM group, whereas the PTFE group lost -2.2 ± 1.5 mm, which was not statistically significant between groups (P > 0.05). Vertical ridge height change was -1.2 ± 1.5 for the CM group, whereas the PTFE group lost -0.5 ± 1.6, which was not significantly different between groups (P > 0.05). The percent vital bone was similar and not significantly different between groups. Primary closure was not obtained and the exposed membrane portion over the socket opening healed with keratinized tissue. The choice of a resorbable versus a nonresorbable barrier membrane did not affect the clinical or the histologic outcome of ridge preservation treatment.

  13. TRAF Family Member-Associated NF-κB Activator (TANK) Induced by RANKL Negatively Regulates Osteoclasts Survival and Function

    OpenAIRE

    Mengrui Wu, Yiping Wang, Lianfu Deng, Wei Chen, Yi-Ping Li

    2012-01-01

    Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation...

  14. TRAF Family Member-Associated NF-κB Activator (TANK) Induced by RANKL Negatively Regulates Osteoclasts Survival and Function

    OpenAIRE

    Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

    2012-01-01

    Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and...

  15. Injection resorbable polymer shells for soft tissue augmentation

    CSIR Research Space (South Africa)

    Naidoo, Kersch

    2008-11-01

    Full Text Available CSIR researchers have developed an injectable, resorbable soft tissue bulking product that has potential applications in fields ranging from heart and recontructive surgery, to minimally invasive cosmetic surgery. Biomaterials research is very...

  16. Medium-Term Function of a 3D Printed TCP/HA Structure as a New Osteoconductive Scaffold for Vertical Bone Augmentation: A Simulation by BMP-2 Activation

    Directory of Open Access Journals (Sweden)

    Mira Moussa

    2015-04-01

    Full Text Available Introduction: A 3D-printed construct made of orthogonally layered strands of tricalcium phosphate (TCP and hydroxyapatite has recently become available. The material provides excellent osteoconductivity. We simulated a medium-term experiment in a sheep calvarial model by priming the blocks with BMP-2. Vertical bone growth/maturation and material resorption were evaluated. Materials and methods: Titanium hemispherical caps were filled with either bare- or BMP-2 primed constructs and placed onto the calvaria of adult sheep (n = 8. Histomorphometry was performed after 8 and 16 weeks. Results: After 8 weeks, relative to bare constructs, BMP-2 stimulation led to a two-fold increase in bone volume (Bare: 22% ± 2.1%; BMP-2 primed: 50% ± 3% and a 3-fold decrease in substitute volume (Bare: 47% ± 5%; BMP-2 primed: 18% ± 2%. These rates were still observed at 16 weeks. The new bone grew and matured to a haversian-like structure while the substitute material resorbed via cell- and chemical-mediation. Conclusion: By priming the 3D construct with BMP-2, bone metabolism was physiologically accelerated, that is, enhancing vertical bone growth and maturation as well as material bioresorption. The scaffolding function of the block was maintained, leaving time for the bone to grow and mature to a haversian-like structure. In parallel, the material resorbed via cell-mediated and chemical processes. These promising results must be confirmed in clinical tests.

  17. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

    International Nuclear Information System (INIS)

    Colnot, C.; Huang, S.; Helms, J.

    2006-01-01

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis

  18. Protective Effects of Selected Botanical Agents on Bone

    Directory of Open Access Journals (Sweden)

    James Jam Jolly

    2018-05-01

    Full Text Available Osteoporosis is a serious health problem affecting more than 200 million elderly people worldwide. The early symptoms of this disease are hardly detectable. It causes progressive bone loss, which ultimately renders the patients susceptible to fractures. Osteoporosis must be prevented because the associated fragility fractures result in high morbidity, mortality, and healthcare costs. Many plants used in herbal medicine contain bioactive compounds possessing skeletal protective effects. This paper explores the anti-osteoporotic properties of selected herbal plants, including their actions on osteoblasts (bone forming cells, osteoclasts (bone resorbing cells, and bone remodelling. Some of the herbal plant families included in this review are Berberidaceae, Fabaceae, Arecaceae, Labiatae, Simaroubaceaea, and Myrsinaceae. Their active constituents, mechanisms of action, and pharmaceutical applications were discussed. The literature shows that very few herbal plants have undergone human clinical trials to evaluate their pharmacological effects on bone to date. Therefore, more intensive research should be performed on these plants to validate their anti-osteoporotic properties so that they can complement the currently available conventional drugs in the battle against osteoporosis.

  19. Bone development in the fetus and neonate: role of the calciotropic hormones.

    Science.gov (United States)

    Kovacs, Christopher S

    2011-12-01

    During embryonic and fetal development much of the skeleton initiates as a cartilaginous scaffold, which is progressively resorbed and replaced by bone. Endochondral bone formation continues until the growth plates fuse during puberty. At all life stages adequate delivery of mineral is required for the skeleton to achieve and maintain appropriate mineral content and strength. During fetal development the placenta actively transports calcium, phosphorus, and magnesium. Postnatally passive and then active absorption from the intestines becomes the main supply of minerals to the skeleton. Animal and human data indicate that fetal bone development requires parathyroid hormone (PTH) and PTH-related protein but not vitamin D/calcitriol, calcitonin, or (possibly) sex steroids. During the postnatal period, when intestinal calcium absorption becomes an active process, skeletal development begins to depend upon vitamin D/calcitriol but this requirement can be bypassed by increasing the calcium content of the diet or by administering intermittent calcium infusions.

  20. Influence of bone affinity on the skeletal distribution of fluorescently labeled bisphosphonates in vivo.

    Science.gov (United States)

    Roelofs, Anke J; Stewart, Charlotte A; Sun, Shuting; Błażewska, Katarzyna M; Kashemirov, Boris A; McKenna, Charles E; Russell, R Graham G; Rogers, Michael J; Lundy, Mark W; Ebetino, Frank H; Coxon, Fraser P

    2012-04-01

    Bisphosphonates are widely used antiresorptive drugs that bind to calcium. It has become evident that these drugs have differing affinities for bone mineral; however, it is unclear whether such differences affect their distribution on mineral surfaces. In this study, fluorescent conjugates of risedronate, and its lower-affinity analogues deoxy-risedronate and 3-PEHPC, were used to compare the localization of compounds with differing mineral affinities in vivo. Binding to dentine in vitro confirmed differences in mineral binding between compounds, which was influenced predominantly by the characteristics of the parent compound but also by the choice of fluorescent tag. In growing rats, all compounds preferentially bound to forming endocortical as opposed to resorbing periosteal surfaces in cortical bone, 1 day after administration. At resorbing surfaces, lower-affinity compounds showed preferential binding to resorption lacunae, whereas the highest-affinity compound showed more uniform labeling. At forming surfaces, penetration into the mineralizing osteoid was found to inversely correlate with mineral affinity. These differences in distribution at resorbing and forming surfaces were not observed at quiescent surfaces. Lower-affinity compounds also showed a relatively higher degree of labeling of osteocyte lacunar walls and labeled lacunae deeper within cortical bone, indicating increased penetration of the osteocyte canalicular network. Similar differences in mineralizing surface and osteocyte network penetration between high- and low-affinity compounds were evident 7 days after administration, with fluorescent conjugates at forming surfaces buried under a new layer of bone. Fluorescent compounds were incorporated into these areas of newly formed bone, indicating that "recycling" had occurred, albeit at very low levels. Taken together, these findings indicate that the bone mineral affinity of bisphosphonates is likely to influence their distribution within the

  1. Histological Evaluation of Degradable Guided Bone Regeneration Membranes Prepared from Poly(trimethylene carbonate) and Biphasic Calcium Phosphate Composites

    NARCIS (Netherlands)

    Zeng, Ni; van Leeuwen, Anne; Bos, Ruud R.M.; Grijpma, Dirk W.; Kuijer, Roel

    2013-01-01

    In oral and maxillofacial surgery, guided bone regeneration using barrier membranes is an important strategy to treat bone defects. The currently used barrier membranes have important disadvantages. Barrier membranes prepared from resorbable poly(trimethylene carbonate) (PTMC) performed as well as

  2. Histological evaluation of degradable guided bone regeneration membranes prepared from poly(trimethylene carbonate) and biphasic calcium phosphate composites

    NARCIS (Netherlands)

    Zeng, Ni; van Leeuwen, Anne; Bos, Ruud R.M.; Grijpma, Dirk W.; Kuijer, Roel

    2013-01-01

    In oral and maxillofacial surgery, guided bone regeneration using barrier membranes is an important strategy to treat bone defects. The currently used barrier membranes have important disadvantages. Barrier membranes prepared from resorbable poly(trimethylene carbonate) (PTMC) performed as well as

  3. Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma.

    Science.gov (United States)

    Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W; Novane, Nora; Shah, Jatin J; Davis, Richard E; Hou, Jian; Gagel, Robert F; Yang, Jing

    2016-08-24

    Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP up-regulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP up-regulated the methylation of IRF8 and thereby enhanced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1 protein), leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2-deoxy-d-ribose (2DDR). Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K (phosphoinositide 3-kinase)/Akt signaling, and increased DNMT3A (DNA methyltransferase 3A) expression, resulting in hypermethylation of RUNX2, osterix, and IRF8 This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. Because TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. Copyright © 2016, American Association for the Advancement of Science.

  4. Endoscopic outcomes of resorbable nasal packing after functional endoscopic sinus surgery: a multicenter prospective randomized controlled study.

    Science.gov (United States)

    Berlucchi, Marco; Castelnuovo, Paolo; Vincenzi, Andrea; Morra, Bruno; Pasquini, Ernesto

    2009-06-01

    Nasal packings can aid in control of postoperative bleeding and healing following functional endoscopic sinus surgery (FESS), but traditional non-resorbable stents have several inherent drawbacks. We performed a randomized, controlled, multicenter clinical trial to assess efficacy of resorbable nasal packing in patients undergoing FESS for chronic rhinosinusitis. A total of 66 patients for 88 nasal cavities were randomized to receive either hyaluronan resorbable packing (MeroGel) or standard non-resorbable nasal dressing after FESS. All underwent preoperative rhinoscopy, CT of sinuses, and, after surgery, were reassessed by rhinoscopy at 2, 4, and 12 weeks in blinded fashion. A total of 44 nasal cavities (MeroGel-group) received resorbable packing, whereas the remaining 44 were packed with non-resorbable nasal dressing. At follow-up endoscopic visit, the presence of nasal synechia was evaluated as primary outcome. Moreover, the tolerability and surgical handling properties of MeroGel and its comfort were assessed by surgeons and patients. Preoperative severity of rhinosinusitis was similar in both groups. No significant adverse events were observed in all patients. Follow-up endoscopy showed a lower proportion of nasal adhesions in MeroGel-group at both 4 (P = 0.041) and 12 weeks (P appearance of nasal mucosa of nasal cavities after FESS was observed in the MeroGel-group. Tolerability and surgical handling properties of MeroGel were positively rated by clinicians and the overall patient judged comfort of MeroGel was favorable. In conclusion, MeroGel can be considered a valid alternative to standard non-resorbable nasal dressings. It is safe, well-accepted, well-tolerated, and has significant advantage of being resorbable. Moreover, it may favor improved healing in patients undergoing FESS and reduce formation of adhesions.

  5. Development of Novel Biodegradable Amino Acid Ester Based Polyphosphazene-Hydroxyapatite Composites for Bone Tissue Engineering

    National Research Council Canada - National Science Library

    Sethuraman, Swaminathan; Nair, Lakshmi S; Singh, Anurima; Bender, Jared D; Greish, Yaser E; Brown, Paul W; Allcock, H. R; Laurencin, Cato T

    2005-01-01

    .... CPCs are attractive candidates for the development of scaffolds for bone tissue engineering, since they are moldable, resorbable, set at physiological temperature without the use of toxic chemicals...

  6. Dynamics of bone graft healing around implants

    Directory of Open Access Journals (Sweden)

    Narayan Venkataraman

    2015-01-01

    A few questions arise pertaining to the use of bone grafts along with implants are whether these are successful in approximation with implant. Do they accelerate bone regeneration? Are all defects ultimately regenerated with new viable bone? Is the bone graft completely resorbed or integrated in new bone? Does the implant surface characteristic positively affect osseointegration when used with a bone graft? What type of graft and implant surface can be used that will have a positive effect on the healing type and time? Finally, what are the dynamics of bone graft healing around an implant? This review discusses the cellular and molecular mechanisms of bone graft healing in general and in vicinity of another foreign, avascular body, namely the implant surface, and further, the role of bone grafts in osseointegration and/or clinical success of the implants.

  7. A rapidly resorbable hemostatic biomaterial based on dihydroxyacetone

    NARCIS (Netherlands)

    Henderson, Peter W.; Kadouch, Daniel J. M.; Singh, Sunil P.; Zawaneh, Peter N.; Weiser, Jennifer; Yazdi, Sara; Weinstein, Andrew; Krotscheck, Ursula; Wechsler, Bennett; Putnam, David; Spector, Jason A.

    2010-01-01

    We have developed a rapid acting, rapidly resorbable, non-toxic, topical hemostatic agent comprised of a PEGylated, polymerized sequence of dihydroxyacetone (MPEG-pDHA) that is highly effective in vivo. Twenty-eight Sprague-Dawley rats underwent left lateral hepatectomy. To the cut edge of the

  8. A prospective clinical evaluation of the longevity of resorbable ...

    African Journals Online (AJOL)

    2012-09-15

    Sep 15, 2012 ... Key words: Evaluation, longevity, oral, resorbable sutures, surgical procedure. Date of ... presence of saliva, specific microbiota, high vascularization, as well as its ..... documented the mean survival of vicryl in the oral cavity.

  9. Comparative Efficacies of a 3D-Printed PCL/PLGA/β-TCP Membrane and a Titanium Membrane for Guided Bone Regeneration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jin-Hyung Shim

    2015-10-01

    Full Text Available This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid/β-tricalcium phosphate (PCL/PLGA/β-TCP membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes using extrusion-based 3D printing technology; mechanical tensile testing and in vitro cell proliferation testing were performed. Implant surgery and guided bone regeneration were performed randomly in three groups (a no membrane group, a titanium membrane group, and a PCL/PLGA/β-TCP membrane group (n = 8 per group. Histological and histometric analyses were conducted to evaluate effects on bone regeneration and osseointegration. Using the results of mechanical testing; a PCL/PLGA/β-TCP ratio of 2:6:2 was selected. The new bone areas (% in buccal defects around implants were highest in the PCL/PLGA/β-TCP group and significantly higher than in the control group (p < 0.05. Bone-to-implant contact ratios (% were also significantly higher in the PCL/PLGA/β-TCP and titanium groups than in the control group (p < 0.05. When the guided bone regeneration procedure was performed using the PCL/PLGA/β-TCP membrane; new bone formation around the implant and osseointegration were not inferior to those of the non-resorbable pre-formed titanium mesh membrane.

  10. Involvement of Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-induced Incomplete Cytokinesis in the Polyploidization of Osteoclasts*

    Science.gov (United States)

    Takegahara, Noriko; Kim, Hyunsoo; Mizuno, Hiroki; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Tomura, Michio; Kanagawa, Osami; Ishii, Masaru; Choi, Yongwon

    2016-01-01

    Osteoclasts are specialized polyploid cells that resorb bone. Upon stimulation with receptor activator of nuclear factor-κB ligand (RANKL), myeloid precursors commit to becoming polyploid, largely via cell fusion. Polyploidization of osteoclasts is necessary for their bone-resorbing activity, but the mechanisms by which polyploidization is controlled remain to be determined. Here, we demonstrated that in addition to cell fusion, incomplete cytokinesis also plays a role in osteoclast polyploidization. In in vitro cultured osteoclasts derived from mice expressing the fluorescent ubiquitin-based cell cycle indicator (Fucci), RANKL induced polyploidy by incomplete cytokinesis as well as cell fusion. Polyploid cells generated by incomplete cytokinesis had the potential to subsequently undergo cell fusion. Nuclear polyploidy was also observed in osteoclasts in vivo, suggesting the involvement of incomplete cytokinesis in physiological polyploidization. Furthermore, RANKL-induced incomplete cytokinesis was reduced by inhibition of Akt, resulting in impaired multinucleated osteoclast formation. Taken together, these results reveal that RANKL-induced incomplete cytokinesis contributes to polyploidization of osteoclasts via Akt activation. PMID:26670608

  11. Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption

    OpenAIRE

    van't Hof, R. J.; Armour, K. J.; Smith, L. M.; Armour, K. E.; Wei, X. Q.; Liew, F. Y.; Ralston, S. H.

    2000-01-01

    Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study,...

  12. "Ruffled border" formation on a CaP-free substrate: A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over.

    Science.gov (United States)

    Merolli, Antonio; Fung, Stephanie; Murthy, N Sanjeeva; Pashuck, E Thomas; Mao, Yong; Wu, Xiaohuan; Steele, Joseph A M; Martin, Daniel; Moghe, Prabhas V; Bromage, Timothy; Kohn, Joachim

    2018-03-21

    Osteoclasts are large multinucleated giant cells that actively resorb bone during the physiological bone turnover (BTO), which is the continuous cycle of bone resorption (by osteoclasts) followed by new bone formation (by osteoblasts). Osteoclasts secrete chemotactic signals to recruit cells for regeneration of vasculature and bone. We hypothesize that a biomaterial that attracts osteoclasts and re-establishes BTO will induce a better healing response than currently used bone graft materials. While the majority of bone regeneration efforts have focused on maximizing bone deposition, the novelty in this approach is the focus on stimulating osteoclastic resorption as the starter for BTO and its concurrent new vascularized bone formation. A biodegradable tyrosine-derived polycarbonate, E1001(1k), was chosen as the polymer base due to its ability to support bone regeneration in vivo. The polymer was functionalized with a RGD peptide or collagen I, or blended with β-tricalcium phosphate. Osteoclast attachment and early stages of active resorption were observed on all substrates. The transparency of E1001(1k) in combination with high resolution confocal imaging enabled visualization of morphological features of osteoclast activation such as the formation of the "actin ring" and the "ruffled border", which previously required destructive forms of imaging such as transmission electron microscopy. The significance of these results is twofold: (1) E1001(1k) is suitable for osteoclast attachment and supports osteoclast maturation, making it a base polymer that can be further modified to optimize stimulation of BTO and (2) the transparency of this polymer makes it a suitable analytical tool for studying osteoclast behavior.

  13. Bioactive silica nanoparticles reverse age-associated bone loss in mice.

    Science.gov (United States)

    Weitzmann, M Neale; Ha, Shin-Woo; Vikulina, Tatyana; Roser-Page, Susanne; Lee, Jin-Kyu; Beck, George R

    2015-05-01

    We recently reported that in vitro, engineered 50nm spherical silica nanoparticles promote the differentiation and activity of bone building osteoblasts but suppress bone-resorbing osteoclasts. Furthermore, these nanoparticles promote bone accretion in young mice in vivo. We have now investigated the capacity of these nanoparticles to reverse bone loss in aged mice, a model of human senile osteoporosis. Aged mice received nanoparticles weekly and bone mineral density (BMD), bone structure, and bone turnover were quantified. Our data revealed a significant increase in BMD, bone volume, and biochemical markers of bone formation. Biochemical and histological examinations failed to identify any abnormalities caused by nanoparticle administration. Our studies demonstrate that silica nanoparticles effectively blunt and reverse age-associated bone loss in mice by a mechanism involving promotion of bone formation. The data suggest that osteogenic silica nanoparticles may be a safe and effective therapeutic for counteracting age-associated bone loss. Osteoporosis poses a significant problem in the society. Based on their previous in-vitro findings, the authors' group investigated the effects of spherical silica nanoparticles in reversing bone loss in a mouse model of osteoporosis. The results showed that intra-peritoneal injections of silica nanoparticles could increase bone mineral density, with little observed toxic side effects. This novel method may prove important in future therapy for combating osteoporosis. Published by Elsevier Inc.

  14. Evaluation of the bone microstructures after the mandibular reconstruction, using bioresorbable hydroxyapatite/poly-L-lactide mesh tray and the particulate cancellous bone

    International Nuclear Information System (INIS)

    Takahashi, Hidetoshi; Matsuo, Akira; Chiba, Hiroshige

    2010-01-01

    The combination of particulate cancellous bone and marrow (PCBM) and a titanium tray is frequently used for mandibular reconstruction. However, there are difficulties in bending the tray and forming a suitable contour. In addition, the metallic ions elute into the living body and the hinders the implant insertion; therefore, a removable operation is required after reconstruction. Hydroxyapatite/poly-L-lactide (HA/PLLA) is a bone-bonding material that has both bio-activity and bio-resorbability. It may overcome the weakness of a titanium tray, but the bone microstructures have not been evaluated after the use of this tray for PCBM reconstruction. We created defects on the mandible of a beagle and reconstructed it by filling it with a mixture of PCBM and PRP using the HA/PLLA tray. We examined the bone-formation mechanism using a confocal laser microscope and bone microstructural analysis using microCT. As a result, compared to the titanium tray, the bone-formation is delayed during the first 3 to 6 months with an HA/PLLA tray. However, a formation of new bone with equal quality is observed after 12 months. According to the bone microstructural measurement, both of them had higher bone volume fraction than the native bone but other parameters were the same. From the above, the quantity of the new bone in the HA/PLLA tray is the same as the bone in the titanium tray, and has equal bone microstructures with the surrounding native bone. (author)

  15. No effect of Osteoset, a bone graft substitute, on bone healing in humans: a prospective randomized double-blind study

    DEFF Research Database (Denmark)

    Petruskevicius, Juozas; Nielsen, Mette Strange; Kaalund, Søren

    2002-01-01

    We studied the effects of a newly marketed bone substitute, Osteoset, on bone healing in a tibial defect in humans. 20 patients undergoing an ACL (anterior cruciate ligament) reconstruction with bone-patella tendon-bone graft were block-randomized into 2 groups of 10 each. In the treatment group......, the tibial defect was filled manually with Osteoset pellets, in the control group the defect was left empty. CTs of the defect were taken on the first day after the operation, 6 weeks, 3 and 6 months postoperatively. We found about the same amount of bone in the defect in the Osteoset and control groups...... after 6 weeks, 3, and 6 months. In the control group, but not in the Osteoset group, the bone volume increased from 6 weeks to 3 months. The Osteoset pellets were almost resorbed after 6 weeks....

  16. Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction.

    Science.gov (United States)

    Iwamoto, Yoriko; Nishikawa, Keizo; Imai, Ryusuke; Furuya, Masayuki; Uenaka, Maki; Ohta, Yumi; Morihana, Tetsuo; Itoi-Ochi, Saori; Penninger, Josef M; Katayama, Ichiro; Inohara, Hidenori; Ishii, Masaru

    2016-06-01

    Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor κB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  17. Protocol for Bone Augmentation with Simultaneous Early Implant Placement: A Retrospective Multicenter Clinical Study

    Directory of Open Access Journals (Sweden)

    Peter Fairbairn

    2015-01-01

    Full Text Available Purpose. To present a novel protocol for alveolar bone regeneration in parallel to early implant placement. Methods. 497 patients in need of extraction and early implant placement with simultaneous bone augmentation were treated in a period of 10 years. In all patients the same specific method was followed and grafting was performed utilizing in situ hardening fully resorbable alloplastic grafting materials consisting of β-tricalcium phosphate and calcium sulfate. The protocol involved atraumatic extraction, implant placement after 4 weeks with simultaneous bone augmentation, and loading of the implant 12 weeks after placement and grafting. Follow-up periods ranged from 6 months to 10 years (mean of 4 years. Results. A total of 601 postextraction sites were rehabilitated in 497 patients utilizing the novel protocol. Three implants failed before loading and three implants failed one year after loading, leaving an overall survival rate of 99.0%. Conclusions. This standardized protocol allows successful long-term functional results regarding alveolar bone regeneration and implant rehabilitation. The concept of placing the implant 4 weeks after extraction, augmenting the bone around the implant utilizing fully resorbable, biomechanically stable, alloplastic materials, and loading the implant at 12 weeks seems to offer advantages when compared with traditional treatment modalities.

  18. Multicellular tumor spheroid interactions with bone cells and bone

    International Nuclear Information System (INIS)

    Wezeman, F.H.; Guzzino, K.M.; Waxler, B.

    1985-01-01

    In vitro coculture techniques were used to study HSDM1C1 murine fibrosarcoma multicellular tumor spheroid (HSDM1C1-MTS) interactions with mouse calvarial bone cells having osteoblastic characteristics and mouse bone explants. HSDM1C1-MTS attached to confluent bone cell monolayers and their attachment rate was quantified. HSDM1C1-MTS interaction with bone cells was further demonstrated by the release of 3 H-deoxyuridine from prelabeled bone cells during coculture with multicellular tumor spheroids. HSDM1C1-MTS-induced cytotoxicity was mimicked by the addition of 10(-5) M prostaglandin E2 (PGE2) to 3 H-deoxyuridine-labeled bone cells. The effects of low (10(-9) M) and high (10(-5) M) concentrations of PGE2 on bone cell proliferation were also studied. Higher concentrations of PGE2 inhibited bone cell proliferation. HSDM1C1-MTS resorbed living explants in the presence of indomethacin, suggesting that other tumor cell products may also participate in bone resorption. HSDM1C1-MTS caused direct bone resorption as measured by the significantly elevated release of 45 Ca from prelabeled, devitalized calvaria. However, the growth of a confluent bone cell layer on devitalized, 45 Ca-prelabeled calvaria resulted in a significant reduction in the amount of 45 Ca released subsequent to the seeding of HSDM1C1-MTS onto the explants. Bone cells at the bone surface may act as a barrier against invasion and tumor cell-mediated bone resorption. Violation of this cellular barrier is achieved, in part, by tumor cell products

  19. Does collagen trigger the recruitment of osteoblasts into vacated bone resorption lacunae during bone remodeling?

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Søe, Kent; Andersen, Thomas Levin

    2014-01-01

    matrix molecules, collagen's potency was superior and only equaled by fibronectin. Next, the majority of the newly recruited osteoblast lineage cells positioned immediately next to the osteoclasts exhibit uPARAP/Endo180, an endocytic collagen receptor reported to be involved in collagen internalization......Osteoblast recruitment during bone remodeling is obligatory to re-construct the bone resorbed by the osteoclast. This recruitment is believed to be triggered by osteoclast products and is therefore likely to start early during the remodeling cycle. Several osteoclast products with osteoblast...... recruitment potential are already known. Here we draw the attention on the osteoblast recruitment potential of the collagen that is freshly demineralized by the osteoclast. Our evidence is based on observations on adult human cancellous bone, combined with in vitro assays. First, freshly eroded surfaces where...

  20. Bone metabolism in the fetus and neonate.

    Science.gov (United States)

    Kovacs, Christopher S

    2014-05-01

    During embryonic development most of the skeleton begins as a cartilaginous scaffold that is progressively resorbed and replaced by bone. Such endochondral bone development does not cease until the growth plates fuse during puberty. Growth and mineralization of the skeleton are dependent upon the adequate delivery of mineral. During fetal development, the placenta actively transports calcium, magnesium and phosphorus from the maternal circulation. After birth, the role of mineral transport is assumed by the intestines. The limited data currently available on fetal humans are largely based on cord blood samples from normal fetuses and pathological specimens from fetuses which died in utero or at birth. Consequently, much of our understanding of the regulation of fetal mineral and bone homeostasis comes from the study of animal fetuses that have been manipulated surgically, pharmacologically and genetically. Animal and human data indicate that fetal mineral homeostasis requires parathyroid hormone (PTH) and PTH-related protein-but not vitamin D/calcitriol, calcitonin or sex steroids. In the days to weeks after birth, intestinal calcium absorption becomes an active process, which necessitates that the infant depends upon vitamin D/calcitriol. However, even this postnatal function of calcitriol can be bypassed by increasing the calcium content of the diet or by administering calcium infusions.

  1. Lost salt technique for severely resorbed alveolar ridges: An innovative approach

    Directory of Open Access Journals (Sweden)

    Himanshi Aggarwal

    2012-01-01

    Full Text Available The success of a complete denture relies on the principles of retention, stability and support. The prosthodontist skill lies in applying these principles efficiently in critical situations. Severely resorbed maxillary edentulous ridges that are narrow and constricted with increased inter ridge space provide decreased support, retention and stability. The consequent weight of the processed denture only compromises them further. This article describes a case report of an edentulous patient with resorbed ridges where a simplified technique of fabricating a hollow maxillary complete denture using lost salt technique was used for preservation of denture bearing areas. The hollowing of the denture reduces the weight of the denture, thereby enhancing stability and retention, reducing the further resorption of the jaws.

  2. Involvement of Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-induced Incomplete Cytokinesis in the Polyploidization of Osteoclasts.

    Science.gov (United States)

    Takegahara, Noriko; Kim, Hyunsoo; Mizuno, Hiroki; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Tomura, Michio; Kanagawa, Osami; Ishii, Masaru; Choi, Yongwon

    2016-02-12

    Osteoclasts are specialized polyploid cells that resorb bone. Upon stimulation with receptor activator of nuclear factor-κB ligand (RANKL), myeloid precursors commit to becoming polyploid, largely via cell fusion. Polyploidization of osteoclasts is necessary for their bone-resorbing activity, but the mechanisms by which polyploidization is controlled remain to be determined. Here, we demonstrated that in addition to cell fusion, incomplete cytokinesis also plays a role in osteoclast polyploidization. In in vitro cultured osteoclasts derived from mice expressing the fluorescent ubiquitin-based cell cycle indicator (Fucci), RANKL induced polyploidy by incomplete cytokinesis as well as cell fusion. Polyploid cells generated by incomplete cytokinesis had the potential to subsequently undergo cell fusion. Nuclear polyploidy was also observed in osteoclasts in vivo, suggesting the involvement of incomplete cytokinesis in physiological polyploidization. Furthermore, RANKL-induced incomplete cytokinesis was reduced by inhibition of Akt, resulting in impaired multinucleated osteoclast formation. Taken together, these results reveal that RANKL-induced incomplete cytokinesis contributes to polyploidization of osteoclasts via Akt activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Study of irradiated bone: Part III. /sup 99m/Tc pyrophosphate autoradiographic changes

    International Nuclear Information System (INIS)

    King, M.A.; Corriveau, O.; Casarett, G.W.; Weber, D.A.

    1978-01-01

    The macroautoradiographic and microautoradiographic localization of /sup 99m/Tc-pyrophosphate (/sup 99m/TcPPi) was studied in x-irradiated bone of rabbits up to one year post-irradiation. In cortical bone, /sup 99m/TcPPi was concentrated on bone surfaces near vasculature. Both forming and resorbing bone surfaces were comparably labeled at 2 hrs post-injection. Uptake on the surface of sites of haversian bone remodeling was observed to be at least part of the increased /sup 99m/TcPPi observed in irradiated bone in camera images. In irradiated trabecular bone 12 months following irradiation, a patchy decrease in /sup 99m/TcPPi uptake was correlated with localized decreases in vasculature

  4. Histone Deacetylases in Bone Development and Skeletal Disorders

    Science.gov (United States)

    Bradley, Elizabeth W.; Carpio, Lomeli R.; van Wijnen, Andre J.; McGee-Lawrence, Meghan E.; Westendorf, Jennifer J.

    2015-01-01

    Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn2+ for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2+. Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of-function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the utility of

  5. Determination of the most appropriate stress distribution by Finite Element Analysis in fixation with resorbable screws after Bilateral Sagittal Split Ramus Osteotomy surgery

    Directory of Open Access Journals (Sweden)

    Sarkarat F.

    2009-12-01

    Full Text Available "nBackground and Aim: Due to the complications associated with fixation by Titanium screws and plates in Bilateral Sagittal Split Ramus Osteotomy (BSSRO surgery, the use of resorbable polymers has been increasingly recommended. Since there are not enough studies on this issue, this study aimed to assess the most appropriate stress distribution in fixation with resorbable screws after BSSRO surgery by Fnite Element Analysis (FEA."nMaterials and Methods: This experimental study was performed on simulated human mandible using Ansys and Catia softwares. The osteotomy line was applied to the simulated model and experimental loads of 75, 135 and 600 N were respectively exerted according to the natural direction of occlusal force. The distribution pattern of stress was assessed and compared for fixation with one resorbable screw, two resorbable screws in vertical pattern, two resorbable screws in horizontal pattern, three resorbable screws in L pattern and three resorbable screws in inverted backward L pattern using Ansys software."nResults: Among the four simulated fixations, L pattern showed the highest primary stability. Two screws in vertical pattern were also associated with sufficient primary stability and less trauma and cost for patients. One screw did not provide enough stability under 600 N."nConclusion: Polymer-based resorbable screws (polyglycolic acid and D, L polylactide acid provided satisfactory primary stability in BSSRO surgery.

  6. An adaptation model for trabecular bone at different mechanical levels

    Directory of Open Access Journals (Sweden)

    Lv Linwei

    2010-07-01

    Full Text Available Abstract Background Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of bone formed and what is resorbed, should be different. Methods An adaptation model for the trabecular bone at different mechanical levels was presented in this study based on a number of experimental observations and numerical algorithms in the literature. In the proposed model, the amount of bone formation and the probability of bone remodeling activation were proposed in accordance with the mechanical levels. Seven numerical simulation cases under different mechanical conditions were analyzed as examples by incorporating the adaptation model presented in this paper with the finite element method. Results The proposed bone adaptation model describes the well-known bone adaptation behaviors in different zones. The bone mass and architecture of the bone tissue within the adaptation zone almost remained unchanged. Although the probability of osteoclastic activation is enhanced in the overload zone, the potential of osteoblasts to form bones compensate for the osteoclastic resorption, eventually strengthening the bones. In the disuse zone, the disuse-mode remodeling removes bone tissue in disuse zone. Conclusions The study seeks to provide better understanding of the relationships between bone morphology and the mechanical, as well as biological environments. Furthermore, this paper provides a computational model and methodology for the numerical simulation of changes of bone structural morphology that are caused by changes of mechanical and biological

  7. Osteosíntesis maxilofacial con materiales reabsorbibles Maxillofacial osteosynthesis with resorbable material

    Directory of Open Access Journals (Sweden)

    J.L. López-Cedrún Cembranos

    2004-12-01

    Full Text Available La popularización de la combinación de ácidos poliláctico y poliglicólico ha hecho que estos nuevos materiales se utilicen cada vez más en la osteosíntesis maxilofacial, no solo en su aplicación pediátrica, sino también en adultos. Aunque todavía presentan algunas desventajas en relación con el titanio, como la mayor incomodidad de uso y el coste económico, la experiencia acumulada demuestra que es una alternativa válida a la osteosíntesis con titanio en la mayoría de las situaciones clínicas. En este artículo se analizan las características y cualidades de los materiales reabsorbibles empleados en osteosíntesis maxilofacial. Así mismo, se discuten las ventajas y desventajas de ambos tipos de osteosíntesis y se documentan las indicaciones actuales de la osteosíntesis reabsorbible basándonos en nuestra experiencia y en la revisión de la literatura.Resorbable plates and screws composed of polylactic and polyglycolic acid, as internal fixation devices have gained widespread use during recent years in pediatric and also adult patients. Although these materials show some disadvantages when compared with titanium plates, such as discomfort and economical cost, accumulated experience shows that resorbable ostheosynthesis is a reliable alternative to the titanium osteosynthesis used in most clinical cases. In this paper we analyze the main characteristics of resorbable materials used in maxillofacial osteosynthesis. We discuss the advantages and disadvantages of both types of osteosynthesis and the indications for resorbable ostheosynthesis at the present time, based on our experience and on a revision of the literature.

  8. Tissue reaction and material characteristics of four bone substitutes

    DEFF Research Database (Denmark)

    Jensen, S S; Aaboe, M; Pinholt, E M

    1996-01-01

    and Interpore 500 HA/CC) were implanted into 5-mm bur holes in rabbit tibiae. There was no difference in the amount of newly formed bone around the four biomaterials. Interpore 500 HA/CC resorbed completely, whereas the other three biomaterials did not undergo any detectable biodegradation. Bio......The aim of the present study was to qualitatively and quantitatively compare the tissue reactions around four different bone substitutes used in orthopedic and craniofacial surgery. Cylinders of two bovine bone substitutes (Endobon and Bio-Oss) and two coral-derived bone substitutes (Pro Osteon 500......-Oss was osseointegrated to a higher degree than the other biomaterials. Material characteristics obtained by diffuse reflectance infrared Fourier transform spectrometry analysis and energy-dispersive spectrometry did not explain the differences in biologic behavior....

  9. Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute: an experimental study in dogs

    DEFF Research Database (Denmark)

    Jensen, T B; Overgaard, S; Lind, M

    2007-01-01

    Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules...... (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant...... surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three...

  10. Evaluation of resorbable membrane in treatment of human gingival isolated buccal recession

    Directory of Open Access Journals (Sweden)

    Sumit Narang

    2011-01-01

    Conclusion: Resorbable membrane is a versatile treatment modality for coverage of isolated buccal gingival recession. Although membrane exposure occurred in four patients, it did not interfere with post operative healing.

  11. Space Maintenance and New Bone Formation with Polyurethane Biocomposites in a Canine Saddle Defect

    Science.gov (United States)

    2014-05-01

    Vanderbilt University, Nashville, TN 2. Medtronic Spinal and Biologics, Memphis, TN 3. US Army Institute of Surgical Research, Fort Sam Houston, TX...and 15% hydroxyapatite (HA) that is similar in mineral content to natural bone.3 45S5 Bioactive glass (BG) is a resorbable material that has been... used effectively in a variety of bone regeneration applications.4 In the present study, we investigated the ability of injectable PUR/MG and PUR/BG

  12. Nutritional factors affecting poultry bone health.

    Science.gov (United States)

    Fleming, Robert H

    2008-05-01

    Outlined are two main current research concerns relating to skeletal disorders in poultry: (a) osteoporosis in egg-laying hens; (b) leg problems caused by rapid bone growth in broiler chickens. Surveys indicate that 30% of caged laying hens suffer at least one lifetime fracture (a severe welfare issue). Modern hybrids produce one egg per d for 50 weeks. For this period 'normal' bone turnover ceases; only medullary bone (MB) is formed, a woven bone type of limited structural value. MB is resorbed for eggshell formation alongside structural bone, leading to increased fracture risk. Avian osteoporosis is reduced by activity and genetic selection but nutrition is also important. Fluoride and vitamin K are beneficial but the timing of nutritional intervention is important. Ca, inorganic P and vitamin D must be adequate and the form of Ca is critical. Limestone fed as particulates benefits skeletal and eggshell quality. In hens fed particulate limestone compared with flour-fed hens the tibiotarsus breaking strength and radiographic density are increased at 56 weeks of age (Pbroiler (meat) chickens selection for rapid growth from approximately 50 g to 3 kg in 42 d has inadvertently produced skeletal disorders such as tibial dyschondroplasia, rickets and associated valgus-varus deformities leading to lameness. The beneficial skeletal effects during growth of increased dietary n-3 PUFA:n-6 PUFA (utilising salmon oil) have been demonstrated. Experiments simulating daylight UVB levels have produced beneficial skeletal effects in Ca- and vitamin D-deficient chicks.

  13. Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1.

    Directory of Open Access Journals (Sweden)

    Shinya Nakamura

    Full Text Available Trimethylation of histone H3 lysine 4 and lysine 27 (H3K4me3 and H3K27me3 at gene promoter regions critically regulates gene expression. Key developmental genes tend to exhibit changes in histone modification patterns from the H3K4me3/H3K27me3 bivalent pattern to the H3K4me3 monovalent pattern. Using comprehensive chromatin immunoprecipitation followed by sequencing in bone marrow-derived macrophages (BMMs and mature osteoclasts, we found that cell surface adhesion molecule 1 (Cadm1 is a direct target of nuclear factor of activated T cells 1 (NFATc1 and exhibits a bivalent histone pattern in BMMs and a monovalent pattern in osteoclasts. Cadm1 expression was upregulated in BMMs by receptor activator of nuclear factor kappa B ligand (RANKL, and blocked by a calcineurin/NFATc1 inhibitor, FK506. Cadm1-deficient mice exhibited significantly reduced bone mass compared with wild-type mice, which was due to the increased osteoclast differentiation, survival and bone-resorbing activity in Cadm1-deficient osteoclasts. These results suggest that Cadm1 is a direct target of NFATc1, which is induced by RANKL through epigenetic modification, and regulates osteoclastic bone resorption in a negative feedback manner.

  14. Resorbable triangular plate for osteosynthesis of fractures of the condylar neck.

    Science.gov (United States)

    Lauer, Günter; Pradel, Winnie; Leonhardt, Henry; Loukota, Richard; Eckelt, Uwe

    2010-10-01

    We describe a new design of resorbable plate for use in the treatment of fractures of the condylar neck, and report the outcome of initial treatment in two patients. Copyright © 2009 The British Association of Oral and Maxillofacial Surgeons. All rights reserved.

  15. Osteoblast and osteoclast behaviors in the turnover of attachment bones during medaka tooth replacement.

    Science.gov (United States)

    Mantoku, Akiko; Chatani, Masahiro; Aono, Kazushi; Inohaya, Keiji; Kudo, Akira

    2016-01-15

    Tooth replacement in polyphyodont is a well-organized system for maintenance of homeostasis of teeth, containing the dynamic structural change in skeletal tissues such as the attachment bone, which is the supporting element of teeth. Histological analyses have revealed the character of tooth replacement, however, the cellular mechanism of how skeletal tissues are modified during tooth replacement is largely unknown. Here, we showed the important role of osteoblasts for controlling osteoclasts to modify the attachment bone during tooth replacement in medaka pharyngeal teeth, coupled with an osterix-DsRed/TRAP-GFP transgenic line to visualize osteoblasts and osteoclasts. In the turnover of the row of attachment bones, these bones were resorbed at the posterior side where most developed functional teeth were located, and generated at the anterior side where teeth were newly erupted, which caused continuous tooth replacement. In the cellular analysis, osteoclasts and osteoblasts were located at attachment bones separately, since mature osteoclasts were localized at the resorbing side and osteoblasts gathered at the generating side. To demonstrate the role of osteoclasts in tooth replacement, we established medaka made deficient in c-fms-a by TALEN. c-fms-a deficient medaka showed hyperplasia of attachment bones along with reduced bone resorption accompanied by a low number of TRAP-positive osteoclasts, indicating an important role of osteoclasts in the turnover of attachment bones. Furthermore, nitroreductase-mediated osteoblast-specific ablation induced disappearance of osteoclasts, indicating that osteoblasts were essential for maintenance of osteoclasts for the proper turnover. Taken together, our results suggested that the medaka attachment bone provides the model to understand the cellular mechanism for tooth replacement, and that osteoblasts act in the coordination of bone morphology by supporting osteoclasts. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. In Vivo Performance of Bilayer Hydroxyapatite Scaffolds for Bone Tissue Regeneration in the Rabbit Radius

    Science.gov (United States)

    2011-02-02

    no treatments and the pres- ence of periosteal callus-like layer surrounding defects with scaffold implantation were observed after 8 weeks post...vivo evaluation of resorbable bone graft substitutes in a rabbit tibial defect model. Biomaterials. 2004; 25(20):5037–44. 20. Lu JX, Gallur A, Flautre

  17. Physical activity effects on bone metabolism.

    Science.gov (United States)

    Smith, E L; Gilligan, C

    1991-01-01

    The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.

  18. Vertical distraction of the severely resorbed mandible - The Groningen Distraction Device

    NARCIS (Netherlands)

    Raghoebar, GM; Heydenrijk, K; Vissink, A

    2000-01-01

    In this paper, both the surgical procedure and the clinical results of a novel distraction device to augment a severely resorbed anterior edentulous mandible are described. The distraction device is non-voluminous, and consists of two distraction screws and one guide screw. Two months after the last

  19. In vivo study of magnesium plate and screw degradation and bone fracture healing.

    Science.gov (United States)

    Chaya, Amy; Yoshizawa, Sayuri; Verdelis, Kostas; Myers, Nicole; Costello, Bernard J; Chou, Da-Tren; Pal, Siladitya; Maiti, Spandan; Kumta, Prashant N; Sfeir, Charles

    2015-05-01

    Each year, millions of Americans suffer bone fractures, often requiring internal fixation. Current devices, like plates and screws, are made with permanent metals or resorbable polymers. Permanent metals provide strength and biocompatibility, but cause long-term complications and may require removal. Resorbable polymers reduce long-term complications, but are unsuitable for many load-bearing applications. To mitigate complications, degradable magnesium (Mg) alloys are being developed for craniofacial and orthopedic applications. Their combination of strength and degradation make them ideal for bone fixation. Previously, we conducted a pilot study comparing Mg and titanium devices with a rabbit ulna fracture model. We observed Mg device degradation, with uninhibited healing. Interestingly, we observed bone formation around degrading Mg, but not titanium, devices. These results highlighted the potential for these fixation devices. To better assess their efficacy, we conducted a more thorough study assessing 99.9% Mg devices in a similar rabbit ulna fracture model. Device degradation, fracture healing, and bone formation were evaluated using microcomputed tomography, histology and biomechanical tests. We observed device degradation throughout, and calculated a corrosion rate of 0.40±0.04mm/year after 8 weeks. In addition, we observed fracture healing by 8 weeks, and maturation after 16 weeks. In accordance with our pilot study, we observed bone formation surrounding Mg devices, with complete overgrowth by 16 weeks. Bend tests revealed no difference in flexural load of healed ulnae with Mg devices compared to intact ulnae. These data suggest that Mg devices provide stabilization to facilitate healing, while degrading and stimulating new bone formation. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. Bone grafting of alveolar socket and ovate seat pontic preparation for natural emergence profile for anterior bridge - A case report

    Directory of Open Access Journals (Sweden)

    Vijay Deshmukh

    2009-01-01

    Full Text Available Alveolar atrophy following tooth extraction remains a challenge for future prosthetic restorations. Immediate implant placement and postextraction alveolar bone grafting are two methods that are used to prevent significant postextraction bone loss. Grafting is one of the most common methods of socket preservation widely used to prevent the collapse of oral tissues following extraction so that an excellent esthetic prosthesis can be provided particularly in the anterior maxillary region. The present report describes the management of a maxillary tooth extraction socket using a socket preservation technique involving placement of an osteoconductive slowly resorbable grafting material & resorbable collagen membrane in the extraction socket also called as Bio-Col socket preservation technique followed by a provisional restoration to preserve the tissues & interdental papilla for the placement of future final ovate pontic anterior bridge to give the illusion of the tooth emerging from the gums. This technique resulted in a successful prevention of alveolar bone loss following tooth extraction & maintainence of tissue contour & density which provided a good tissue base for the fabrication of Ovate pontic giving excellent esthetic results.

  1. Bone bonding at natural and biomaterial surfaces.

    Science.gov (United States)

    Davies, John E

    2007-12-01

    Bone bonding is occurring in each of us and all other terrestrial vertebrates throughout life at bony remodeling sites. The surface created by the bone-resorbing osteoclast provides a three-dimensionally complex surface with which the cement line, the first matrix elaborated during de novo bone formation, interdigitates and is interlocked. The structure and composition of this interfacial bony matrix has been conserved during evolution across species; and we have known for over a decade that this interfacial matrix can be recapitulated at a biomaterial surface implanted in bone, given appropriate healing conditions. No evidence has emerged to suggest that bone bonding to artificial materials is any different from this natural biological process. Given this understanding it is now possible to explain why bone-bonding biomaterials are not restricted to the calcium-phosphate-based bioactive materials as was once thought. Indeed, in the absence of surface porosity, calcium phosphate biomaterials are not bone bonding. On the contrary, non-bonding materials can be rendered bone bonding by modifying their surface topography. This paper argues that the driving force for bone bonding is bone formation by contact osteogenesis, but that this has to occur on a sufficiently stable recipient surface which has micron-scale surface topography with undercuts in the sub-micron scale-range.

  2. Calcium and bone metabolism disorders during pregnancy and lactation.

    Science.gov (United States)

    Kovacs, Christopher S

    2011-12-01

    Pregnancy and lactation cause a substantial increase in demand for calcium that is met by different maternal adaptations within each period. Intestinal calcium absorption more than doubles during pregnancy, whereas the maternal skeleton resorbs to provide most of the calcium content of breast milk during lactation. These maternal adaptations also affect the presentation, diagnosis, and management of disorders of calcium and bone metabolism. Although some women may experience fragility fractures as a consequence of pregnancy or lactation, for most women, parity and lactation do not affect the long-term risks of low bone density, osteoporosis, or fracture. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Clinical management of highly resorbed mandibular ridge without fibrous tissue

    Directory of Open Access Journals (Sweden)

    Veeramalai N Devaki

    2012-01-01

    Full Text Available Alveolar ridge atrophy poses a clinical challenge toward the fabrication of successful prosthesis. Resorption of mandibular denture bearing areas results in unstable non-retentive dentures associated with pain and discomfort. This article describes rehabilitation procedure of a patient with resorbed ridge with maximal areas of coverage to improve support and neutral zone arrangement of teeth to improve stability of denture.

  4. Bulletin of Materials Science | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    A resorbable composite which acts as a active barrier in guided bone regeneration was fabricated using chitosan, demineralized bone matrix and bone ash. Its potential to form bone like apatite in simulated body fluid was assessed in this study. The mechanical strength of these composites was correlated with bone ash ...

  5. Comparing membranes and bone substitutes in a one-stage procedure for horizontal bone augmentation. A double-blind randomised controlled trial.

    Science.gov (United States)

    Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Pagliaro, Umberto; Raffaelli, Eugenia; Nieri, Michele

    2015-01-01

    The objective of this parallel randomised controlled trial is to compare two bone substitutes and collagen membranes in a one-stage procedure for horizontal bone augmentation: anorganic bovine bone (Bio-Oss) and collagen porcine membranes (Bio-Gide) (BB group) versus a synthetic resorbable bone graft substitute made of pure β-tricalcium phosphate (Ceros TCP) and porcine pericardium collagen membranes (Jason) (CJ group). Patients in need of implant treatment having at least one site with horizontal osseous defects at a private clinic in Rimini (Italy) were included in this study. Patients were randomised to receive either the BB or CJ treatment. Randomisation was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes. Patients and the outcome assessor were blinded to group assignment. The main outcome measures were implant failure, complications, clinical bone gain at augmented sites, and complete filling of the bone defect. Secondary outcome measures were chair-time, postoperative pain and peri-implant marginal bone level changes. Twenty-five patients with 32 implants were allocated to the BB group and 25 patients with 29 implants to the CJ group. All 50 randomised patients received the treatment as allocated and there were no dropouts up to 6-months post-loading (12 months post-surgery). There were no failures and there were three complications in the BB group and three complications in the CJ group (relative risk: 1.00, 95% CI from 0.22 to 4.49, P = 1.00). The estimated difference between treatments in the vertical defect bone gain was -0.15 mm (95% CI from -0.65 to 0.35, P = 0.5504) favouring the BB group, and the estimated difference between treatments in the horizontal defect bone gain was -0.27 mm (95%CI from -0.73 to 0.19, P = 0.3851) favouring the BB group. There was no difference in the complete filling of the defect (relative risk: 0.88, 95%CI from 0.58 to 1.34, P = 0.7688). No significant differences were

  6. Magnetic forces and magnetized biomaterials provide dynamic flux information during bone regeneration.

    Science.gov (United States)

    Russo, Alessandro; Bianchi, Michele; Sartori, Maria; Parrilli, Annapaola; Panseri, Silvia; Ortolani, Alessandro; Sandri, Monica; Boi, Marco; Salter, Donald M; Maltarello, Maria Cristina; Giavaresi, Gianluca; Fini, Milena; Dediu, Valentin; Tampieri, Anna; Marcacci, Maurilio

    2016-03-01

    The fascinating prospect to direct tissue regeneration by magnetic activation has been recently explored. In this study we investigate the possibility to boost bone regeneration in an experimental defect in rabbit femoral condyle by combining static magnetic fields and magnetic biomaterials. NdFeB permanent magnets are implanted close to biomimetic collagen/hydroxyapatite resorbable scaffolds magnetized according to two different protocols . Permanent magnet only or non-magnetic scaffolds are used as controls. Bone tissue regeneration is evaluated at 12 weeks from surgery from a histological, histomorphometric and biomechanical point of view. The reorganization of the magnetized collagen fibers under the effect of the static magnetic field generated by the permanent magnet produces a highly-peculiar bone pattern, with highly-interconnected trabeculae orthogonally oriented with respect to the magnetic field lines. In contrast, only partial defect healing is achieved within the control groups. We ascribe the peculiar bone regeneration to the transfer of micro-environmental information, mediated by collagen fibrils magnetized by magnetic nanoparticles, under the effect of the static magnetic field. These results open new perspectives on the possibility to improve implant fixation and control the morphology and maturity of regenerated bone providing "in site" forces by synergically combining static magnetic fields and biomaterials.

  7. Treatment of Severely Resorbed Maxilla Due to Peri-Implantitis by Guided Bone Regeneration Using a Customized Allogenic Bone Block: A Case Report

    Directory of Open Access Journals (Sweden)

    Oliver Blume

    2017-10-01

    Full Text Available The objective of this case report is to introduce a customized CAD/CAM freeze-dried bone allograft (FDBA block for its use in Guided Bone Regeneration (GBR procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show optimal integration behavior of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept.

  8. Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells?

    Science.gov (United States)

    Miron, Richard J; Zohdi, Hamoon; Fujioka-Kobayashi, Masako; Bosshardt, Dieter D

    2016-12-01

    Recently accumulating evidence has put into question the role of large multinucleated giant cells (MNGCs) around bone biomaterials. While cells derived from the monocyte/macrophage lineage are one of the first cell types in contact with implanted biomaterials, it was originally thought that specifically in bone tissues, all giant cells were bone-resorbing osteoclasts whereas foreign body giant cells (FBGCs) were found associated with a connective tissue foreign body reaction resulting in fibrous encapsulation and/or material rejection. Despite the great majority of bone grafting materials routinely found with large osteoclasts, a special subclass of bone biomaterials has more recently been found surrounded by large giant cells virtually incapable of resorbing bone grafts even years after their implantation. While original hypotheses believed that a 'foreign body reaction' may be taking place, histological data retrieved from human samples years after their implantation have put these original hypotheses into question by demonstrating better and more stable long-term bone volume around certain bone grafts. Exactly how or why this 'special' subclass of giant cells is capable of maintaining long-term bone volume, or methods to scientifically distinguish them from osteoclasts remains extremely poorly studied. The aim of this review article was to gather the current available literature on giant cell markers and differences in expression patterns between osteoclasts and MNGCs utilizing 19 specific markers including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (previously referred to as FBGCs) as well as wound-healing M2-MNGCs is introduced and discussed. This review article presents 19 specific cell-surface markers to distinguish between osteoclasts and MNGCs including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (often

  9. P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis

    DEFF Research Database (Denmark)

    Wang, Ning; Agrawal, Ankita; Jørgensen, Niklas Rye

    2018-01-01

    Post-menopausal osteoporosis is a condition that affects millions worldwide and places a huge socio-economic burden on society. Previous research has shown an association of loss of function SNPs in the gene for the purinergic receptor P2X7R with low bone mineral density, increased rates of bone...... loss and vertebral fractures in post-menopausal women. In this study we use a mouse model of oestrogen deficiency-induced bone loss and the BALB/cJ P2X7R-/- to show that absence of the P2X7R resulted in increased bone loss. Osteoclast precursors were isolated from both BALB/cJ P2X7R-/- and BALB/cJ P2X7......R+/+ mice and then cultured in vitro to form mature resorbing osteoclasts. The BALB/cJ P2X7R-/- derived precursors generated slightly more osteoclasts but with a significant reduction in the amount of resorption per osteoclast. Furthermore, when using modified culture conditions osteoclast activity...

  10. Bone cutting capacity and osseointegration of surface-treated orthodontic mini-implants.

    Science.gov (United States)

    Kim, Ho-Young; Kim, Sang-Cheol

    2016-11-01

    The objective of the study was to evaluate the practicality and the validity of different surface treatments of self-drilling orthodontic mini-implants (OMIs) by comparing bone cutting capacity and osseointegration. Self-drilling OMIs were surface-treated in three ways: Acid etched (Etched), resorbable blasting media (RBM), partially resorbabla balsting media (Hybrid). We compared the bone cutting capacity by measuring insertion depths into artificial bone (polyurethane foam). To compare osseointegration, OMIs were placed in the tibia of 25 rabbits and the removal torque value was measured at 1, 2, 4, and 8 weeks after placement. The specimens were analyzed by optical microscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). The bone cutting capacity of the etched and hybrid group was lower than the machined (control) group, and was most inhibited in the RBM group ( p drilling OMIs, without a corresponding reduction in bone cutting capacity.

  11. Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model

    OpenAIRE

    Zhang, Haifeng; Mao, Xiyuan; Du, Zijing; Jiang, Wenbo; Han, Xiuguo; Zhao, Danyang; Han, Dong; Li, Qingfeng

    2016-01-01

    Abstract We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500??m and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, ?-tricalcium phosphate (?-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, prolife...

  12. Fibrous scaffolds for bone tissue engineering: static and dynamic in vitro studies with MG63 cells

    Czech Academy of Sciences Publication Activity Database

    Buczynska, J.; Pamula, E.; Blazewicz, S.; Bačáková, Lucie; Pařízek, Martin; Chlupáč, Jaroslav; Mikolajczyk, T.; Boguň, M.; Dobrzynski, P.

    2007-01-01

    Roč. 10, 65-66 (2007), s. 1-6 ISSN 1429-7248 R&D Projects: GA ČR(CZ) GA106/06/1576 Grant - others:-(PL) 3T08D 023 30 Institutional research plan: CEZ:AV0Z50110509 Keywords : resorbable scaffolds * bioarteficial bone * dynamic cell culture system Subject RIV: EI - Biotechnology ; Bionics

  13. On a new law of bone remodeling based on damage elasticity: a thermodynamic approach

    Directory of Open Access Journals (Sweden)

    Idhammad Ahmed

    2012-11-01

    Full Text Available Abstract Background Bone tissue is the main element of the human skeleton and is a dynamic tissue that is continuously renewed by bone-resorbing osteoclasts and bone-forming osteoblasts. The bone is also capable of repairing itself and adapting its structure to changes in its load environment through the process of bone remodeling. Therefore, this phenomenon has been gaining increasing interest in the last years and many laws have been developed in order to simulate this process. Results In this paper, we develop a new law of bone remodeling in the context of damaged elastic by applying the thermodynamic approach in the case of small perturbations. The model is solved numerically by a finite difference method in the one-dimensional bone structure of a n-unit elements model. Conclusion In addition, several numerical simulations are presented that confirm the accuracy and effectiveness of the model.

  14. Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Nakamura, Ryosuke; Kayamori, Kou; Oue, Erika; Sakamoto, Kei; Harada, Kiyoshi; Yamaguchi, Akira

    2015-01-01

    Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and the bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC

  15. Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Ryosuke [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Kayamori, Kou [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Oue, Erika [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Sakamoto, Kei [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Harada, Kiyoshi [Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan)

    2015-03-20

    Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and the bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC

  16. Clinical use of the resorbable bioscaffold poly lactic co-glycolic acid (PLGA) in post-extraction socket for maintaining the alveolar height: A prospective study.

    Science.gov (United States)

    Hoda, Nadeemul; Saifi, Aamir Malick; Giraddi, Girish B

    2016-01-01

    A common sequel of tooth extraction is alveolar bone resorption. It makes the placement of dental implants difficult and creates an esthetic problem for the fabrication of conventional prostheses. Therefore, alveolar bone following tooth extraction should be preserved. The present prospective study was conducted to evaluate the efficacy of the resorbable bioscaffold poly lactic co-glycolic acid (PLGA) in maintaining the alveolar height in post-extraction socket. 20 patients were selected based on inclusion and exclusion criteria and were randomly divided into two groups: cases and control comprising of 10 patients each. Atraumatic tooth extraction was done in all patients. PLGA bioscaffold was placed in cases and socket was closed with 3-0 vicryl. In control group, socket was directly closed with 3-0 vicryl. The patients were kept on follow-up and complications such as dry socket, pain, and swelling were recorded. IOPA were taken at 1st, 4th, 12th, and 24th week to record changes in the height of alveolar bone. The radiographic measurements were compared and the differences were statistically analyzed. Reduction in alveolar bone height after placement of PLGA bioscaffold was significantly less in cases as compared to controls at 4th, 12th, and 24th week following extraction. No complications were observed throughout the follow-up period. PLGA scaffold significantly reduces bone resorption. Application is very simple and can be easily performed in a dental setup. However, PLGA scaffold adds significantly to the cost of treatment.

  17. Alveolar distraction osteogenesis: revive and restore the native bone.

    Science.gov (United States)

    Sant, Sumedha; Jagtap, Amit

    2009-12-01

    In prosthodontics, knife-edge bony alveolar ridges can cause a problem in their rehabilitation. The distraction osteogenesis process raises the medullary component of the alveolus, allowing the labial plate of the existing natural bone to be displaced. This process involves mobilization, transport, and fixation of a healthy segment of bone adjacent to the deficient site. It entails use of the gradual controlled displacement of surgically created fractures, which results in simultaneous expansion of soft tissue and bone volume. A mechanical device, the alveolar distraction device, is used for this purpose. This modality of treatment can be used in implant dentistry cases for rehabilitation of resorbed ridges. The objective of this overview is to explain this procedure wherein the alveolar housing, including the osseous and soft-tissue components, is enlarged in a single, simultaneous process, which makes creation of an appropriate alveolar morphology possible.

  18. In vivo bone regeneration using a novel porous bioactive composite

    Energy Technology Data Exchange (ETDEWEB)

    Xie En [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Hu Yunyu [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China)], E-mail: orth1@fmmn.edu.cn; Chen Xiaofeng [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Bai Xuedong; Li Dan [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Ren Li [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Zhang Ziru [Foreign Languages School, Northwest University Xi' an (China)

    2008-11-15

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

  19. In vivo bone regeneration using a novel porous bioactive composite

    International Nuclear Information System (INIS)

    Xie En; Hu Yunyu; Chen Xiaofeng; Bai Xuedong; Li Dan; Ren Li; Zhang Ziru

    2008-01-01

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications

  20. Osteoclast inhibition impairs chondrosarcoma growth and bone destruction.

    Science.gov (United States)

    Otero, Jesse E; Stevens, Jeff W; Malandra, Allison E; Fredericks, Douglas C; Odgren, Paul R; Buckwalter, Joseph A; Morcuende, Jose

    2014-12-01

    Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. Long-term results of bone-retinaculum-bone autograft for scapholunate instability.

    Science.gov (United States)

    Soong, Maximillian; Merrell, Gregory A; Ortmann, Fred; Weiss, Arnold-Peter C

    2013-03-01

    To report long-term follow-up of scapholunate interosseous ligament reconstruction with bone-retinaculum-bone autograft in patients with dynamic scapholunate instability. Of the 14 patients from the previously reported cohort who had bone-retinaculum-bone autograft for dynamic instability, 6 returned for clinical examination and radiographs, 3 were reached by telephone, and 2 were lost to follow-up. The remaining 3 had salvage procedures (2 total wrist arthrodeses and 1 proximal row carpectomy) between the prior report and the current study and thus reached an endpoint, at 2 to 4 years. For the 6 who returned, outcome measurements included scapholunate angle and gap, radiographic evidence of secondary arthritis, wrist extension and flexion, grip strength, and Mayo wrist score. Follow-up averaged 11.9 years (range, 10.7-14.1 y). Clinical and radiographic outcomes deteriorated moderately from the prior report. Mayo wrist score averaged 83. There were 3 failures, resulting in 1 proximal row carpectomy and 2 total wrist arthrodeses. Findings at repeat surgery in the failed group included an intact graft without any apparent abnormalities, a partially ruptured graft (after a subsequent re-injury), and a completely resorbed graft. Bone-retinaculum-bone autograft reconstruction is a viable treatment option for dynamic scapholunate instability in which the scaphoid and lunate can be reduced. Results may deteriorate but are similar to those reported previously from other techniques. Problems with graft strength or stiffness may necessitate further surgery. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  2. How Does Physical Activity Help Build Healthy Bones?

    Science.gov (United States)

    ... Share Facebook Twitter Pinterest Email Print How does physical activity help build healthy bones? Bones are living tissue. Weight-bearing physical activity causes new bone tissue to form, and this ...

  3. Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

    Science.gov (United States)

    Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

    2009-11-01

    Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

  4. Peri-Implant Crestal Bone Loss: A Putative Mechanism

    Directory of Open Access Journals (Sweden)

    Yuko Ujiie

    2012-01-01

    Full Text Available Purpose. The immunological mechanisms of peri-implant crestal bone loss have, hitherto, not been elucidated. We hypothesized that bacterial products from the microgap cause upregulation of cytokines in otherwise healthy peri-implant cells, which results in osteoclast formation and, ultimately, in bone resorption. Materials and Methods. We used RT-PCR and ELISA to assay mediators of osteoclastogenesis in rat and human macrophages (r-and hMO; bone marrow derived stromal cells (r-and hBMCs; and human gingival fibroblasts (hGF—with or without stimulation by LPS. TRAP positive multinucleate cells were assessed for their resorptive ability. Results. We show that IL-1α, IL-1β, and IL-6 were expressed by all examined cell types, and TNF-α was upregulated in hGF. Secretion of IL-1α and IL-1β proteins was stimulated in hMO by LPS, and IL-6 protein secretion was highly stimulated in hBMCs and hGF. Both LPS and RANKL stimulated macrophages to form osteoclast-like TRAP positive cells, which resorbed calcium phosphate substrates. Conclusion. Taken together, the results of our study support the hypothesis that bacterial endotoxins upregulate enhanced mediators of osteoclastogenesis in resident cells found in the healthy peri-implant compartment and that the local synergistic action of cytokines secreted by such cells results in the genesis of resorptively active osteoclasts.

  5. The purinergic P2X7 ion channel receptor — a ‘repair’ receptor in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye

    2018-01-01

    A strong skeleton relies on adaptation to varying physical demands and on maintenance of the bone tissue in order to avoid accumulation of micro-damage. In bone, the purinergic P2X7 ion channel receptor is expressed on both cells of the stromal lineage such as the bone forming osteoblasts...... and the mechano-sensing osteocytes and on cells belonging to the immune-related monocyte–macrophage lineage, the bone resorbing osteoclasts. Recent studies have demonstrated that the receptor plays important roles in the anabolic responses to mechanical loading on bone and, together with the pannexin1 hemi......-channel, in the process of initiating bone remodeling in response to micro-damage. Thus, the receptor is crucial in skeletal mechano-transduction and in the continuous repair process. However, under pathophysiological conditions such as diabetes with high glucose concentrations or glucocorticoid-treatment the receptor...

  6. New mechanisms and targets in the treatment of bone fragility.

    Science.gov (United States)

    Martin, T John; Seeman, Ego

    2007-01-01

    Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with

  7. Posterior lumbar interbody fusion using non resorbable poly-ether-ether-ketone versus resorbable poly-L-lactide-co-D,L-lactide fusion devices. Clinical outcome at a minimum of 2-year follow-up

    NARCIS (Netherlands)

    Jiya, T.U.; Smit, T.H.; van Royen, B.J.; Mullender, M.G.

    2011-01-01

    Previous papers on resorbable poly-L-lactideco-D,L-lactide (PLDLLA) cages in spinal fusion have failed to report adequately on patient-centred clinical outcome measures. Also comparison of PLDLLA cage with a traditionally applicable counterpart has not been previously reported. This is the first

  8. Tricalcium phosphate based resorbable ceramics: Influence of NaF and CaO addition

    Energy Technology Data Exchange (ETDEWEB)

    Seeley, Zachary; Bandyopadhyay, Amit [W. M. Keck Biomedical Materials Research Lab, School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164 (United States); Bose, Susmita [W. M. Keck Biomedical Materials Research Lab, School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164 (United States)], E-mail: sbose@wsu.edu

    2008-01-10

    Resorbable bioceramics have gained much attention due to their time-varying mechanical properties in-vivo. Implanted ceramics degrade allowing bone in-growth and eventual replacement of the artificial material with natural tissue. Calcium phosphate based materials have caught the most significant attention because of their excellent biocompatibility and compositional similarities to natural bone. Doping these ceramics with various metal ions has significantly influenced their properties. In this study, tricalcium phosphate (TCP) compacts were fabricated via uniaxial compression with five compositions: (i) pure TCP, (ii) TCP with 2.0 wt.% NaF, (iii) TCP with 3.0 wt.% CaO, (iv) TCP with a binary of 2.0 wt.% NaF and 0.5 wt.% Ag{sub 2}O, and (v) TCP with a quaternary of 1.0 wt.% TiO{sub 2}, 0.5 wt.% Ag{sub 2}O, 2.0 wt.% NaF, and 3.0 wt.% CaO. These compacts were sintered at 1250 deg. C for 4 h to obtain dense ceramic structures. Phase analyses were carried out using X-ray diffraction. The presence of NaF in TCP improved densification and increased compression strength from 70 ({+-} 25) to 130 ({+-} 40) MPa. Addition of CaO had no influence on density or strength. Human osteoblast cell growth behavior was studied using an osteoprecursor cell line (OPC 1) to assure that the biocompatibility of these ceramics was not altered due to the dopants. For long-term biodegradation studies, density, weight change, surface microstructure, and uniaxial compression strength were measured as a function of time in a simulated body fluid (SBF). Weight gain in SBF correlated strongly with precipitation viewed in the inter-connected pores of the samples. After 3 months in SBF, all samples displayed a reduction in strength. NaF, CaO and the quaternary compositions maintained the most steady strength loss under SBF.

  9. Osteoprotegerin in bone metastases: mathematical solution to the puzzle.

    Directory of Open Access Journals (Sweden)

    Marc D Ryser

    Full Text Available Bone is a common site for cancer metastasis. To create space for their growth, cancer cells stimulate bone resorbing osteoclasts. Cytokine RANKL is a key osteoclast activator, while osteoprotegerin (OPG is a RANKL decoy receptor and an inhibitor of osteoclastogenesis. Consistently, systemic application of OPG decreases metastatic tumor burden in bone. However, OPG produced locally by cancer cells was shown to enhance osteolysis and tumor growth. We propose that OPG produced by cancer cells causes a local reduction in RANKL levels, inducing a steeper RANKL gradient away from the tumor and towards the bone tissue, resulting in faster resorption and tumor expansion. We tested this hypothesis using a mathematical model of nonlinear partial differential equations describing the spatial dynamics of OPG, RANKL, PTHrP, osteoclasts, tumor and bone mass. We demonstrate that at lower expression rates, tumor-derived OPG enhances the chemotactic RANKL gradient and osteolysis, whereas at higher expression rates OPG broadly inhibits RANKL and decreases osteolysis and tumor burden. Moreover, tumor expression of a soluble mediator inducing RANKL in the host tissue, such as PTHrP, is important for correct orientation of the RANKL gradient. A meta-analysis of OPG, RANKL and PTHrP expression in normal prostate, carcinoma and metastatic tissues demonstrated an increase in expression of OPG, but not RANKL, in metastatic prostate cancer, and positive correlation between OPG and PTHrP in metastatic prostate cancer. The proposed mechanism highlights the importance of the spatial distribution of receptors, decoys and ligands, and can be applied to other systems involving regulation of spatially anisotropic processes.

  10. Impact of Platform Switching on Peri-Implant Bone Remodeling around Short Implants in the Posterior Region, 1-Year Results from a Split-Mouth Clinical Trial

    NARCIS (Netherlands)

    Telleman, Gerdien; Raghoebar, Gerry M.; Vissink, Arjan; Meijer, Henny J. A.

    Aim: To assess the effect of platform switching on peri-implant bone remodeling around short implants (8.5mm) placed in the resorbed posterior mandibular and maxillary region of partially edentulous patients. Materials and Methods: Seventeen patients with one or more missing teeth at both sides in

  11. Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

    Science.gov (United States)

    Rougraff, Bruce T; Kling, Thomas J

    2002-06-01

    The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

  12. The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss.

    Science.gov (United States)

    Shinohara, Masahiro; Chang, Betty Y; Buggy, Joseph J; Nagai, Yusuke; Kodama, Tatsuhiko; Asahara, Hiroshi; Takayanagi, Hiroshi

    2014-03-01

    Bone-resorbing osteoclasts play an essential role in normal bone homeostasis, as well as in various bone disorders such as osteoporosis and rheumatoid arthritis. Previously we showed that the Tec family of tyrosine kinases is essential for the differentiation of osteoclasts and the inhibition of Btk is a promising strategy for the prevention of the bone loss in osteoclast-associated bone disorders. Here we demonstrate that an orally available Btk inhibitor, ibrutinib (PCI-32765), suppresses osteoclastic bone resorption by inhibiting both osteoclast differentiation and function. Ibrutinib downregulated the expression of NFATc1, the key transcription factor for osteoclastogenesis, and disrupted the formation of the actin ring in mature osteoclasts. In addition, genome-wide screening revealed that Btk regulates the expression of the genes involved in osteoclast differentiation and function in both an NFATc1-dependent and -independent manner. Finally, we showed that ibrutinib administration ameliorated the bone loss that developed in a RANKL-induced osteoporosis mouse model. Thus, this study suggests ibrutinib to be a promising therapeutic agent for osteoclast-associated bone diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Building bone tissue: matrices and scaffolds in physiology and biotechnology

    Directory of Open Access Journals (Sweden)

    Riminucci M.

    2003-01-01

    Full Text Available Deposition of bone in physiology involves timed secretion, deposition and removal of a complex array of extracellular matrix proteins which appear in a defined temporal and spatial sequence. Mineralization itself plays a role in dictating and spatially orienting the deposition of matrix. Many aspects of the physiological process are recapitulated in systems of autologous or xenogeneic transplantation of osteogenic precursor cells developed for tissue engineering or modeling. For example, deposition of bone sialoprotein, a member of the small integrin-binding ligand, N-linked glycoprotein family, represents the first step of bone formation in ectopic transplantation systems in vivo. The use of mineralized scaffolds for guiding bone tissue engineering has revealed unexpected manners in which the scaffold and cells interact with each other, so that a complex interplay of integration and disintegration of the scaffold ultimately results in efficient and desirable, although unpredictable, effects. Likewise, the manner in which biomaterial scaffolds are "resorbed" by osteoclasts in vitro and in vivo highlights more complex scenarios than predicted from knowledge of physiological bone resorption per se. Investigation of novel biomaterials for bone engineering represents an essential area for the design of tissue engineering strategies.

  14. Vancomycin graft composite for infected bone defects

    International Nuclear Information System (INIS)

    Winkler, H.; Janata, O.; Georgopoulos, A.

    1999-01-01

    Reconstructive surgery under septic conditions represents a major challenge in orthopaedics. Local application of antibiotics can provide high drug levels at the site of infection without systemic effects. However, removal of non-resorbable implants and filling of defects usually requires additional operative procedures. An ideal antibiotic carrier should provide for : 1) Effective bactericidal activity, especially against staphylococci including MRSA; 2) High and long lasting levels at the site of infection without local or systemic toxicity; 3) Repair of defects without a second stage procedure. Allogeneic cancellous bone is proven to be effective in restoration of bone stock. Vancomycin is effective against all gram-positive populations and the agent of choice for infections with MRSA. The aim of our study is to investigate the efficacy of a combination of both components in bone infection. Cancellous bone of human origin was processed during several steps and incubated in 10% vancomycin solution. The antimicrobial activity of the vancomycin graft composite (VGC) was evaluated using an agar diffusion bioassay against staphylococcus aureus and high performance liquid chromatography (HPLC). The testing period was up to 9 weeks. Elution of vancomycin from the graft was evaluated in 2.5% human albumin solution, which was exchanged every 24 hours. Concentration of vancomycin in allograft-bone was between 6.653[tg/g and 23.194gg/g with an average of 15.250 [tg/g, which is equivalent to 10.000 times the minimum inhibitory concentration (MIC) for s. aureus. The initial activity decreased to approx. 50% during the first week and approx. 30% at the end of the 9th week. The lowest values measured exceeded the MIC by 2000 times. Concentration in surrounding fluid decreased from 24.395,80 to 18,43pg/ml after 11 complete exchanges. Human cancellous bone, processed in an adequate way, offers capability to store high quantities of vancomycin. Vancomycin graft composites are

  15. Applications of Metals for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Kristina Glenske

    2018-03-01

    Full Text Available The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP-based substitute materials based on natural (allo- and xenografts and synthetic origins (alloplastic materials are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between new bone tissue formation and material degradation has not been found, until now. The addition of different substances such as collagen or growth factors and also of different cell types has already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are used differently as a basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue, playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designed for bone regeneration, with the aim to provide an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.

  16. Alteration In Bones Metabolism In Active Rheumatoid Arthritis

    International Nuclear Information System (INIS)

    Salem, E.S.

    2013-01-01

    The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Osteocalcin (OC) is synthesized by osteoblasts and is considered to be a marker of bone formation and helps in corporating calcium into bone tissue. Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease characterized by bone complication including bone pain, erosion and osteoporosis. The aim of the present study is to evaluate some factors responsible in bone metabolism termed OC, vitamin D (vit. D), oncostatin M (OSM), ionized calcium and alkaline phosphatase. Fifty pre-menopausal female patients with active RA and twenty healthy controls of the same age were included in the present study. Radioimmunoassay (RIA) was used to estimate serum OC and active vitamin D. The quantitative determination of ionized calcium and alkaline phosphatase were carried out colorimetrically. OSM was measured by ELISA and serum levels of OC and active vitamin D were significantly decreased in RA patients as compared to those of the control group. On the other hand, the levels of serum OSM, ionized calcium and alkaline phosphatase were significantly increased in the RA patients as compared to their healthy control subjects. The results of this study indicated that early investigation and therapy of disturbances of bone metabolism in active RA are necessary for better prognosis and exhibited the importance of OC as a diagnostic tool of alterations of bone metabolism in RA patients.

  17. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    International Nuclear Information System (INIS)

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun; Chung, Won-Yoon

    2014-01-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  18. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun, E-mail: biochelab@yuhs.ac; Chung, Won-Yoon, E-mail: wychung@yuhs.ac

    2014-03-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  19. Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model

    Science.gov (United States)

    Zhang, Haifeng; Mao, Xiyuan; Du, Zijing; Jiang, Wenbo; Han, Xiuguo; Zhao, Danyang; Han, Dong; Li, Qingfeng

    2016-01-01

    We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500 μm and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, β-tricalcium phosphate (β-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, proliferation, alkaline phosphatase activity and osteogenic gene expression of osteopontin (OPN) and collagen type I (COL-1). Moreover, the biocompatibility, bone repairing capacity and degradation in three different bone substitute materials were estimated using a critical-size rat calvarial defect model in vivo. The defects were evaluated by micro-computed tomography and histological analysis at four and eight weeks after surgery, respectively. The results showed that each of the studied scaffolds had its own specific merits and drawbacks. Three-dimensional printed PLA/HA scaffolds possessed good biocompatibility and stimulated BMSC cell proliferation and differentiation to osteogenic cells. The outcomes in vivo revealed that 3D printed PLA/HA scaffolds had good osteogenic capability and biodegradation activity with no difference in inflammation reaction. Therefore, 3D printed PLA/HA scaffolds have potential applications in bone tissue engineering and may be used as graft substitutes in reconstructive surgery.

  20. P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis.

    Science.gov (United States)

    Wang, Ning; Agrawal, Ankita; Jørgensen, Niklas Rye; Gartland, Alison

    2018-02-22

    Post-menopausal osteoporosis is a condition that affects millions worldwide and places a huge socio-economic burden on society. Previous research has shown an association of loss of function SNPs in the gene for the purinergic receptor P2X7R with low bone mineral density, increased rates of bone loss and vertebral fractures in post-menopausal women. In this study we use a mouse model of oestrogen deficiency-induced bone loss and the BALB/cJ P2X7R -/- to show that absence of the P2X7R resulted in increased bone loss. Osteoclast precursors were isolated from both BALB/cJ P2X7R -/- and BALB/cJ P2X7R +/+ mice and then cultured in vitro to form mature resorbing osteoclasts. The BALB/cJ P2X7R -/- derived precursors generated slightly more osteoclasts but with a significant reduction in the amount of resorption per osteoclast. Furthermore, when using modified culture conditions osteoclast activity was additionally increased in the absence of the P2X7R suggest that P2X7R may regulate the lifespan and activity of osteoclasts. Finally using mechanical loading as an anabolic stimulus for bone formation, we demonstrated that the increased oestrogen-deficient bone loss could be rescued, even in the absence of P2X7R. This study paves the way for clinical intervention for women with post-menopausal osteoporosis and P2XR7 loss of function polymorphisms.

  1. Imaging of alkaline phosphatase activity in bone tissue.

    Directory of Open Access Journals (Sweden)

    Terence P Gade

    Full Text Available The purpose of this study was to develop a paradigm for quantitative molecular imaging of bone cell activity. We hypothesized the feasibility of non-invasive imaging of the osteoblast enzyme alkaline phosphatase (ALP using a small imaging molecule in combination with (19Flourine magnetic resonance spectroscopic imaging ((19FMRSI. 6, 8-difluoro-4-methylumbelliferyl phosphate (DiFMUP, a fluorinated ALP substrate that is activatable to a fluorescent hydrolysis product was utilized as a prototype small imaging molecule. The molecular structure of DiFMUP includes two Fluorine atoms adjacent to a phosphate group allowing it and its hydrolysis product to be distinguished using (19Fluorine magnetic resonance spectroscopy ((19FMRS and (19FMRSI. ALP-mediated hydrolysis of DiFMUP was tested on osteoblastic cells and bone tissue, using serial measurements of fluorescence activity. Extracellular activation of DiFMUP on ALP-positive mouse bone precursor cells was observed. Concurringly, DiFMUP was also activated on bone derived from rat tibia. Marked inhibition of the cell and tissue activation of DiFMUP was detected after the addition of the ALP inhibitor levamisole. (19FMRS and (19FMRSI were applied for the non-invasive measurement of DiFMUP hydrolysis. (19FMRS revealed a two-peak spectrum representing DiFMUP with an associated chemical shift for the hydrolysis product. Activation of DiFMUP by ALP yielded a characteristic pharmacokinetic profile, which was quantifiable using non-localized (19FMRS and enabled the development of a pharmacokinetic model of ALP activity. Application of (19FMRSI facilitated anatomically accurate, non-invasive imaging of ALP concentration and activity in rat bone. Thus, (19FMRSI represents a promising approach for the quantitative imaging of bone cell activity during bone formation with potential for both preclinical and clinical applications.

  2. [Clinical usefulness of bone turnover markers in the management of osteoporosis].

    Science.gov (United States)

    Yano, Shozo

    2013-09-01

    Osteoporosis is a state of elevated risk for bone fracture due to depressed bone strength, which is considered to be the sum of bone mineral density and bone quality. Since a measure of bone quality has not been established, bone mineral density and bone turnover markers are the only way to evaluate bone strength. Bone turnover markers are classified into bone formation marker and resorption marker, which are correlated with the bone formation rate and resorption rate, respectively, and bone matrix-related marker. Bone is always metabolized; old tissue is resorbed by acids and proteases derived from osteoclasts, whereas new bone is produced by osteoblasts. Bone formation and resorption rates should be balanced (also called coupled). When the bone resorption rate exceeds the formation rate(uncoupled state), bone volume will be reduced. Thus, we can comprehend bone metabolism by measuring both formation and resorption markers at the same time. Increased fracture risk is recognized by elevated bone resorption markers and undercarboxylated osteocalcin, which reflects vitamin K insufficiency and bone turnover. These values and the time course give us helpful information to choose medicine suitable for the patients and to judge the responsiveness. If the value is extraordinarily high without renal failure, metabolic bone disorder or bone metastatic tumor should be considered. Bone quality may be assessed by measuring bone matrix-related markers such as homocystein and pentosidine. Since recent studies indicate that the bone is a hormone-producing organ, it is possible that glucose metabolism or an unknown mechanism could be assessed in the future.

  3. Accidental periapical extrusion of non-setting calcium hydroxide: Unusual bone response and management

    Directory of Open Access Journals (Sweden)

    Divya S Sharma

    2014-01-01

    Full Text Available Premixed non-setting calcium hydroxide is frequently used as interim root canal dressing in endodontically involved permanent teeth and as obturating paste in deciduous teeth in pediatric dentistry. Wide apex in both cases makes it more prone for deliberate extrusion especially when applied with pressure delivery systems. Contrary to common belief the mix was not resorbed in two years with the complaint of insufficiency in mastication. Large mass of calcium hydroxide in bone delayed healing process even after its removal. The present case report intends to demonstrate unusual behavior of bone in response to oily non-setting preparation of calcium hydroxide. Therefore its application with pressure syringe should be reconsidered in pediatric dentistry.

  4. Reconstruction of irradiated bone segmental defects with a biomaterial associating MBCP+(R), microstructured collagen membrane and total bone marrow grafting: an experimental study in rabbits.

    Science.gov (United States)

    Jégoux, Franck; Goyenvalle, Eric; Cognet, Ronan; Malard, Olivier; Moreau, Francoise; Daculsi, Guy; Aguado, Eric

    2009-12-15

    The bone tissue engineering models used today are still a long way from any oncologic application as immediate postimplantation irradiation would decrease their osteoinductive potential. The aim of this study was to reconstruct a segmental critical size defect in a weight-bearing bone irradiated after implantation. Six white New Zealand rabbits were immediately implanted with a biomaterial associating resorbable collagen membrane EZ(R) filled and micro-macroporous biphasic calcium phosphate granules (MBCP+(R)). After a daily schedule of radiation delivery, and within 4 weeks, a total autologous bone marrow (BM) graft was injected percutaneously into the center of the implant. All the animals were sacrificed at 16 weeks. Successful osseous colonization was found to have bridged the entire length of the defects. Identical distribution of bone ingrowth and residual ceramics at the different levels of the implant suggests that the BM graft plays an osteoinductive role in the center of the defect. Periosteum-like formation was observed at the periphery, with the collagen membrane most likely playing a role. This model succeeded in bridging a large segmental defect in weight-bearing bone with immediate postimplantation fractionated radiation delivery. This has significant implications for the bone tissue engineering approach to patients with cancer-related bone defects.

  5. Bone microarchitecture and estimated bone strength in men with active acromegaly.

    Science.gov (United States)

    Silva, Paula P B; Amlashi, Fatemeh G; Yu, Elaine W; Pulaski-Liebert, Karen J; Gerweck, Anu V; Fazeli, Pouneh K; Lawson, Elizabeth; Nachtigall, Lisa B; Biller, Beverly M K; Miller, Karen K; Klibanski, Anne; Bouxsein, Mary; Tritos, Nicholas A

    2017-11-01

    Both acromegaly and adult growth hormone deficiency (GHD) are associated with increased fracture risk. Sufficient data are lacking regarding cortical bone microarchitecture and bone strength, as assessed by microfinite element analysis (µFEA). To elucidate both cortical and trabecular bone microarchitecture and estimated bone strength in men with active acromegaly or GHD compared to healthy controls. Cross-sectional study at a clinical research center, including 48 men (16 with acromegaly, 16 with GHD and 16 healthy controls). Areal bone mineral density (aBMD), cortical and trabecular bone microarchitecture and estimated bone strength (µFEA) at the radius and tibia. aBMD was not different between the 3 groups at any skeletal site. At the radius, patients with acromegaly had greater cortical area ( P  acromegaly had lower trabecular bone density ( P  = 0.0082), but no differences in cortical bone microstructure. Compressive strength and failure load did not significantly differ between groups. These findings persisted after excluding patients with hypogonadism. Bone microarchitecture was not deficient in patients with GHD. Both cortical and trabecular microarchitecture are altered in men with acromegaly. Our data indicate that GH excess is associated with distinct effects in cortical vs trabecular bone compartments. Our observations also affirm the limitations of aBMD testing in the evaluation of patients with acromegaly. © 2017 European Society of Endocrinology.

  6. The proliferative human monocyte subpopulation contains osteoclast precursors

    Science.gov (United States)

    Lari, Roya; Kitchener, Peter D; Hamilton, John A

    2009-01-01

    Introduction Immediate precursors of bone-resorbing osteoclasts are cells of the monocyte/macrophage lineage. Particularly during clinical conditions showing bone loss, it would appear that osteoclast precursors are mobilized from bone marrow into the circulation prior to entering tissues undergoing such loss. The observed heterogeneity of peripheral blood monocytes has led to the notion that different monocyte subpopulations may have special or restricted functions, including as osteoclast precursors. Methods Human peripheral blood monocytes were sorted based upon their degree of proliferation and cultured in macrophage colony-stimulating factor (M-CSF or CSF-1) and receptor activator of nuclear factor-kappa-B ligand (RANKL). Results The monocyte subpopulation that is capable of proliferation gave rise to significantly more multinucleated, bone-resorbing osteoclasts than the bulk of the monocytes. Conclusions Human peripheral blood osteoclast precursors reside in the proliferative monocyte subpopulation. PMID:19222861

  7. Secondary digital nerve repair in the foot with resorbable p(DLLA-epsilon-CL) nerve conduits

    NARCIS (Netherlands)

    Meek, MF; Nicolai, JPA; Robinson, PH

    Nerve guides are increasingly being used in peripheral nerve repair. In the last decade, Much preclinical research has been undertaken into a resorbable nerve guide composed of p(DLLA-epsilon-CL). This report describes the results of secondary digital nerve reconstruction in the foot in a patient

  8. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A. C.; Huddleston Slater, J. J. R.; Gielkens, P. F. M.; de Jong, J. R.; Grijpma, D. W.; Bos, R. R. M.

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague-Dawley rats, a

  9. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A.C.; Huddelston Slater, J.J.R.; Gielkens, P.F.M.; de Jong, J.R.; Grijpma, Dirk W.; Bos, R.R.M.

    2012-01-01

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague–Dawley rats, a

  10. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

    OpenAIRE

    Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo

    2015-01-01

    Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs ...

  11. Synthetic bone substitute material comparable with xenogeneic material for bone tissue regeneration in oral cancer patients: First and preliminary histological, histomorphometrical and clinical results.

    Science.gov (United States)

    Ghanaati, Shahram; Barbeck, Mike; Lorenz, Jonas; Stuebinger, Stefan; Seitz, Oliver; Landes, Constantin; Kovács, Adorján F; Kirkpatrick, Charles J; Sader, Robert A

    2013-07-01

    The present study was first to evaluate the material-specific cellular tissue response of patients with head and neck cancer to a nanocrystalline hydroxyapatite bone substitute NanoBone (NB) in comparison with a deproteinized bovine bone matrix Bio-Oss (BO) after implantation into the sinus cavity. Eight patients with tumor resection for oral cancer and severely resorbed maxillary bone received materials according to a split mouth design for 6 months. Bone cores were harvested prior to implantation and analyzed histologically and histomorphometrically. Implant survival was followed-up to 2 years after placement. Histologically, NB underwent a higher vascularization and induced significantly more tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated giant cells when compared with BO, which induced mainly mononuclear cells. No significant difference was observed in the extent of new bone formation between both groups. The clinical follow-up showed undisturbed healing of all implants in the BO-group, whereas the loss of one implant was observed in the NB-group. Within its limits, the present study showed for the first time that both material classes evaluated, despite their induction of different cellular tissue reactions, may be useful as augmentation materials for dental and maxillofacial surgical applications, particularly in patients who previously had oral cancer.

  12. Matrix metalloproteinase-12 (MMP-12) in osteoclasts

    DEFF Research Database (Denmark)

    Hou, Peng; Troen, Tine; Ovejero, Maria C

    2004-01-01

    Osteoclasts require matrix metalloproteinase (MMP) activity and cathepsin K to resorb bone, but the critical MMP has not been identified. Osteoclasts express MMP-9 and MMP-14, which do not appear limiting for resorption, and the expression of additional MMPs is not clear. MMP-12, also called...... bone show MMP-12 expression in osteoclasts in calvariae and long bones. We also demonstrate that recombinant MMP-12 cleaves the putative functional domains of osteopontin and bone sialoprotein, two bone matrix proteins that strongly influence osteoclast activities, such as attachment, spreading...

  13. Continuous Digital Light Processing (cDLP): Highly Accurate Additive Manufacturing of Tissue Engineered Bone Scaffolds.

    Science.gov (United States)

    Dean, David; Jonathan, Wallace; Siblani, Ali; Wang, Martha O; Kim, Kyobum; Mikos, Antonios G; Fisher, John P

    2012-03-01

    Highly accurate rendering of the external and internal geometry of bone tissue engineering scaffolds effects fit at the defect site, loading of internal pore spaces with cells, bioreactor-delivered nutrient and growth factor circulation, and scaffold resorption. It may be necessary to render resorbable polymer scaffolds with 50 μm or less accuracy to achieve these goals. This level of accuracy is available using Continuous Digital Light processing (cDLP) which utilizes a DLP(®) (Texas Instruments, Dallas, TX) chip. One such additive manufacturing device is the envisionTEC (Ferndale, MI) Perfactory(®). To use cDLP we integrate a photo-crosslinkable polymer, a photo-initiator, and a biocompatible dye. The dye attenuates light, thereby limiting the depth of polymerization. In this study we fabricated scaffolds using the well-studied resorbable polymer, poly(propylene fumarate) (PPF), titanium dioxide (TiO(2)) as a dye, Irgacure(®) 819 (BASF [Ciba], Florham Park, NJ) as an initiator, and diethyl fumarate as a solvent to control viscosity.

  14. Release of lead from bone in pregnancy and lactation

    International Nuclear Information System (INIS)

    Manton, W.I.; Angle, C.R.; Stanek, K.L.; Kuntzelman, D.; Reese, Y.R.; Kuehnemann, T.J.

    2003-01-01

    Concentrations and isotope ratios of lead in blood, urine, 24-h duplicate diets, and hand wipes were measured for 12 women from the second trimester of pregnancy until at least 8 months after delivery. Six bottle fed and six breast fed their infants. One bottle feeder fell pregnant for a second time, as did a breast feeder, and each was followed semicontinuously for totals of 44 and 54 months, respectively. Bone resorption rather than dietary absorption controls changes in blood lead, but in pregnancy the resorption of trabecular and cortical bone are decoupled. In early pregnancy, only trabecular bone (presumably of low lead content) is resorbed, causing blood leads to fall more than expected from hemodilution alone. In late pregnancy, the sites of resorption move to cortical bone of higher lead content and blood leads rise. In bottle feeders, the cortical bone contribution ceases immediately after delivery, but any tendency for blood leads to fall may be compensated by the effect of hemoconcentration produced by the postpartum loss of plasma volume. In lactation, the whole skeleton undergoes resorption and the blood leads of nursing mothers continue to rise, reaching a maximum 6-8 months after delivery. Blood leads fall from pregnancy to pregnancy, implying that the greatest risk of lead toxicity lies with first pregnancies

  15. Adaptor protein GRB2 promotes Src tyrosine kinase activation and podosomal organization by protein-tyrosine phosphatase ϵ in osteoclasts.

    Science.gov (United States)

    Levy-Apter, Einat; Finkelshtein, Eynat; Vemulapalli, Vidyasiri; Li, Shawn S-C; Bedford, Mark T; Elson, Ari

    2014-12-26

    The non-receptor isoform of protein-tyrosine phosphatase ϵ (cyt-PTPe) supports adhesion of bone-resorbing osteoclasts by activating Src downstream of integrins. Loss of cyt-PTPe reduces Src activity in osteoclasts, reduces resorption of mineralized matrix both in vivo and in cell culture, and induces mild osteopetrosis in young female PTPe KO mice. Activation of Src by cyt-PTPe is dependent upon this phosphatase undergoing phosphorylation at its C-terminal Tyr-638 by partially active Src. To understand how cyt-PTPe activates Src, we screened 73 Src homology 2 (SH2) domains for binding to Tyr(P)-638 of cyt-PTPe. The SH2 domain of GRB2 bound Tyr(P)-638 of cyt-PTPe most prominently, whereas the Src SH2 domain did not bind at all, suggesting that GRB2 may link PTPe with downstream molecules. Further studies indicated that GRB2 is required for activation of Src by cyt-PTPe in osteoclast-like cells (OCLs) in culture. Overexpression of GRB2 in OCLs increased activating phosphorylation of Src at Tyr-416 and of cyt-PTPe at Tyr-638; opposite results were obtained when GRB2 expression was reduced by shRNA or by gene inactivation. Phosphorylation of cyt-PTPe at Tyr-683 and its association with GRB2 are integrin-driven processes in OCLs, and cyt-PTPe undergoes autodephosphorylation at Tyr-683, thus limiting Src activation by integrins. Reduced GRB2 expression also reduced the ability of bone marrow precursors to differentiate into OCLs and reduced the fraction of OCLs in which podosomal adhesion structures assume organization typical of active, resorbing cells. We conclude that GRB2 physically links cyt-PTPe with Src and enables cyt-PTPe to activate Src downstream of activated integrins in OCLs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Comparative effectiveness of using resorbable membranes of polylactic acid and collagen in regeneration of bone defects in patients with periimplantitis

    Directory of Open Access Journals (Sweden)

    Gudaryan A.A.

    2014-03-01

    Full Text Available The article presents the results of comparative study of effectiveness of usage of separation membranes from polylactic acid (PLA and collagen in carrying out targeted regeneration of bone tissue in 22 patients with periimplantitis. Purpose: To conduct a comparative clinico-radiological efficiency of PLA membrane and collagen membranes in removing bone defects of the alveolar bone in patients with periimplantitis in clinic. It was found that depending on the type of membrane, bone tissue growth occurs not in the same way. Surgery in treatment of periimplantitis using osteo-inducing agent «Bio-Oss» and PLA membranes allows to reach full recovery of bone in bone defects in 90.9 % of patients versus 63.63 % of cases with collagen membranes. Thus, reconstitution of bone in bone defects in periimplantitis is more of full value in using PLA membranes than with membranes from collagen.

  17. Implantation of tetrapod-shaped granular artificial bones or β-tricalcium phosphate granules in a canine large bone-defect model.

    Science.gov (United States)

    Choi, Sungjin; Liu, I-Li; Yamamoto, Kenichi; Honnami, Muneki; Sakai, Takamasa; Ohba, Shinsuke; Echigo, Ryosuke; Suzuki, Shigeki; Nishimura, Ryouhei; Chung, Ung-Il; Sasaki, Nobuo; Mochizuki, Manabu

    2014-03-01

    We investigated biodegradability and new bone formation after implantation of tetrapod-shaped granular artificial bone (Tetrabone®) or β-tricalcium phosphate granules (β-TCP) in experimental critical-size defects in dogs, which were created through medial and lateral femoral condyles. The defect was packed with Tetrabone® (Tetrabone group) or β-TCP (β-TCP group) or received no implant (control group). Computed tomography (CT) was performed at 0, 4 and 8 weeks after implantation. Micro-CT and histological analysis were conducted to measure the non-osseous tissue rate and the area and distribution of new bone tissue in the defect at 8 weeks after implantation. On CT, β-TCP was gradually resorbed, while Tetrabone® showed minimal resorption at 8 weeks after implantation. On micro-CT, non-osseous tissue rate of the control group was significantly higher compared with the β-TCP and Tetrabone groups (Pbone tissue of the β-TCP group was significantly greater than those of the Tetrabone and control groups (Pbone distribution of the Tetrabone group was significantly greater than those of the β-TCP and control groups (Pbone defects in dogs.

  18. Localized ridge defect augmentation using human pericardium membrane and demineralized bone matrix.

    Science.gov (United States)

    Vidyadharan, Arun Kumar; Ravindran, Anjana

    2014-01-01

    Patient wanted to restore her lost teeth with implants in the lower left first molar and second premolar region. Cone beam computerized tomography (CBCT) revealed inadequate bone width and height around future implant sites. The extraction socket of second premolar area revealed inadequate socket healing with sparse bone fill after 4 months of extraction. To evaluate the clinical feasibility of using a collagen physical resorbable barrier made of human pericardium (HP) to augment localized alveolar ridge defects for the subsequent placement of dental implants. Ridge augmentation was done in the compromised area using Puros® demineralized bone matrix (DBM) Putty with chips and an HP allograft membrane. Horizontal (width) and vertical hard tissue measurements with CBCT were recorded on the day of ridge augmentation surgery, 4 month and 7 months follow-up. Intra oral periapical taken 1 year after implant installation showed minimal crestal bone loss. Bone volume achieved through guided bone regeneration was a gain of 4.8 mm horizontally (width) and 6.8 mm vertically in the deficient ridge within a period of 7 months following the procedure. The results suggested that HP Allograft membrane may be a suitable component for augmentation of localized alveolar ridge defects in conjunction with DBM with bone chips.

  19. [Bone marrow stromal damage mediated by immune response activity].

    Science.gov (United States)

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

  20. Utilization of d-PTFE Barriers for Post-Extraction Bone Regeneration in Preparation for Dental Implants.

    Science.gov (United States)

    Greenstein, Gary; Carpentieri, Joseph R

    2015-01-01

    Guided bone regeneration (GBR) can be used to restore a defective alveolar ridge after extractions before or in combination with implant placement. It may also be employed after extractions to reduce crestal bone resorption and maximize bone fill of sockets. Resorbable or nonresorbable barriers (eg, expanded polytetrafluoroethylene [e-PTFE]) can be used when performing GBR procedures, but they need to be completely submerged to attain optimal results. Dense polytetrafluoroethylene (d-PTFE) is a type of nonresorbable barrier that circumvents the necessity to attain primary closure after placement of bone grafts, thereby reducing patient morbidity. This article addresses topics pertaining to d-PTFE utilization, including characteristics and advantages of d-PTFE barriers, time needed for osteoid tissue to become impervious to penetration by flap connective tissue, relevant clinical studies, and limitations of available data. Clinical photographs and radiographs of successfully treated cases are presented to illustrate the efficacy of d-PTFE barriers in regenerating defective bony plates after extractions.

  1. Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture.

    Science.gov (United States)

    Sanz-Salvador, Lucía; García-Pérez, Miguel Ángel; Tarín, Juan J; Cano, Antonio

    2015-02-01

    Changes in bone density and bone markers suggest that pregnancy is associated with deterioration of bone mass in the mother. The metabolism of calcium resets to allow for the needs imposed by the building of the fetal skeleton. The fetus contributes to the process through the output of regulators from the placenta. Understanding of the whole process is limited, but some changes are unambiguous. There is an increase in the circulating levels of vitamin D, but its functional impact is unclear. Fetal parathyroid hormone (PTH) and PTH-related peptide (PTHrp) play an indirect role through support of a calcium gradient that creates hypercalcemia in the fetus. Placental GH, which increases up to the end of pregnancy, may exert some anabolic effects, either directly or through the regulation of the IGF1 production. Other key regulators of bone metabolism, such as estrogens or prolactin, are elevated during pregnancy, but their role is uncertain. An increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) to osteoprotegerin (OPG) acts as an additional pro-resorbing factor in bone. The increase in bone resorption may lead to osteoporosis and fragility fracture, which have been diagnosed, although rarely. However, the condition is transitory as long-term studies do not link the number of pregnancies with osteoporosis. Prevention is limited by the lack of identifiable risk factors. When fractures are diagnosed, rest, analgesics, or, when indicated, orthopedic intervention have demonstrated efficacy. Systemic treatment with anti-osteoporotic drugs is effective, but the potential harm to the fetus imposes caution in their use. © 2015 European Society of Endocrinology.

  2. In Vitro and In Vivo Study of a Novel Porcine Collagen Membrane for Guided Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Eisner Salamanca

    2016-11-01

    Full Text Available For years, in order to improve bone regeneration and prevent the need of a second stage surgery to remove non-resorbable membranes, biological absorbable membranes have gradually been developed and applied in guided tissue regeneration (GTR. The present study’s main objective was to achieve space maintenance and bone regeneration using a new freeze-dried developed porcine collagen membrane, and compare it with an already commercial collagen membrane, when both were used with a bovine xenograft in prepared alveolar ridge bone defects. Prior to surgery, the membrane’s vitality analysis showed statistically significant higher cell proliferation in the test membrane over the commercial one. In six beagle dogs, commercial bone xenograft was packed in lateral ridge bone defects prepared in the left and right side and then covered with test porcine collagen membrane or commercial collagen membrane. Alveolar height changes were measured. Histomorphometric results, in vitro and in vivo properties indicated that the new porcine collagen membrane is biocompatible, enhances bone xenograft osteoconduction, and reduces the alveolar ridge height reabsorption rate.

  3. Novel bone substitute material in alveolar bone healing following tooth extraction: an experimental study in sheep.

    Science.gov (United States)

    Liu, Jinyi; Schmidlin, Patrick R; Philipp, Alexander; Hild, Nora; Tawse-Smith, Andrew; Duncan, Warwick

    2016-07-01

    Electrospun cotton wool-like nanocomposite (ECWN) is a novel synthetic bone substitute that incorporates amorphous calcium phosphate nanoparticles into a biodegradable synthetic copolymer poly(lactide-co-glycolide). The objectives of this study were to develop a tooth extraction socket model in sheep for bone graft research and to compare ECWN and bovine-derived xenograft (BX) in this model. Sixteen cross-bred female sheep were used. Bilateral mandibular premolars were extracted atraumatically. Second and third premolar sockets were filled (Latin-square allocation) with BX, ECWN or left unfilled. Resorbable collagen membranes were placed over BX and selected ECWN grafted sockets. Eight sheep per time period were sacrificed after 8 and 16 weeks. Resin-embedded undemineralised sections were analysed for descriptive histology and histomorphometric analyses. At 8 weeks, there were with no distinct differences in healing among the different sites. At 16 weeks, osseous healing followed a fine trabecular pattern in ECWN sites. Non-grafted sites showed thick trabeculae separated by large areas of fibrovascular connective tissue. In BX grafted sites, xenograft particles were surrounded by newly formed bone or fibrovascular connective tissue. There were no statistically significant differences in bone formation across the four groups. However, ECWN sites had significantly less residual graft material than BX sites at 16 weeks (P = 0.048). This first description of a tooth extraction socket model in sheep supports the utility of this model for bone graft research. The results of this study suggested that the novel material ECWN did not impede bone ingrowth into sockets and showed evidence of material resorption. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. A Modified Rabbit Ulna Defect Model for Evaluating Periosteal Substitutes in Bone Engineering: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    El Backly, Rania M. [DIMES, University of Genova, Genova (Italy); IRCCS AOU San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genova (Italy); Faculty of Dentistry, Alexandria University, Alexandria (Egypt); Chiapale, Danilo [IRCCS AOU San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genova (Italy); Muraglia, Anita [Biorigen S.R.L., Genova (Italy); Tromba, Giuliana [Sincrotrone Trieste S.C.P.A., Trieste (Italy); Ottonello, Chiara [Biorigen S.R.L., Genova (Italy); Santolini, Federico [IRCCS AOU San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genova (Italy); Cancedda, Ranieri; Mastrogiacomo, Maddalena, E-mail: maddalena.mastrogiacomo@unige.it [DIMES, University of Genova, Genova (Italy); IRCCS AOU San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genova (Italy)

    2015-01-06

    The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX{sup ®}) membrane was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12–16 weeks, and bone regeneration was evaluated by radiography, computed microtomography (μCT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORE-TEX{sup ®}) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitute.

  5. A Modified Rabbit Ulna Defect Model for Evaluating Periosteal Substitutes in Bone Engineering: A Pilot Study

    International Nuclear Information System (INIS)

    El Backly, Rania M.; Chiapale, Danilo; Muraglia, Anita; Tromba, Giuliana; Ottonello, Chiara; Santolini, Federico; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2015-01-01

    The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX ® ) membrane was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12–16 weeks, and bone regeneration was evaluated by radiography, computed microtomography (μCT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORE-TEX ® ) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitute.

  6. A new resorbable device for ligation of blood vessels - A pilot study

    Directory of Open Access Journals (Sweden)

    Borg Niklas

    2011-07-01

    Full Text Available Abstract Background During surgery, controlled haemostasis to prevent blood loss is vital for a successful outcome. It can be difficult to ligate vessels located deep in the abdomen. A device that is easy to use and enables secure ligatures could be beneficial. Cable ties made of nylon have been used for ligation but the non-resorbable material caused tissue reactions. The objective of this study was to use a resorbable material to construct a device with a self-locking mechanism and to test its mechanical strength and ligation efficiency. Methods The device was manufactured by injection moulding of polydioxanone, a resorbable polymer used for suture materials. Polydioxanone with inherent viscosities of 1.9 dL/g and 1.3 dL/g were tested. The device consisted of a perforated flexible band which could be pulled through a case with a locking mechanism. After a first version of the device had been tested, some improvements were made. The locking case was downsized, corners were rounded off, the band was made thicker and the mould was redesigned to produce longer devices. Tensile tests were performed with the second version. The first version of the device was used to ligate the ovarian pedicle in a euthanized dog and to test echogenicity of the device with ultrasound. Compression of vessels of the ovarian pedicle was examined by histology. Both versions of the device were tested for haemostasis of and tissue grip on renal arteries in six anaesthetised pigs. Results The tensile strength of the flexible band of the devices with inherent viscosity of 1.9 dL/g was 50.1 ± 5.5 N (range 35.2-62.9 N, n = 11 and the devices with inherent viscosity of 1.3 dL/g had a tensile strength of 39.8 ± 8.1 N (range 18.6-54.2 N, n = 11. Injection moulding of the polymer with lower inherent viscosity resulted in a longer flow distance. Both versions of the device had an effective tissue grip and complete haemostasis of renal arteries was verified. The device attached

  7. Evaluation of four biodegradable, injectable bone cements in an experimental drill hole model in sheep.

    Science.gov (United States)

    von Rechenberg, Brigitte; Génot, Oliver R; Nuss, Katja; Galuppo, Larry; Fulmer, Mark; Jacobson, Evan; Kronen, Peter; Zlinszky, Kati; Auer, Jörg A

    2013-09-01

    Four cement applications were tested in this investigation. Two dicalcium phosphate dihydrate (DCPD-brushite) hydraulic cements, an apatite hydraulic fiber loaded cement, and a calcium sulfate cement (Plaster of Paris) were implanted in epiphyseal and metaphyseal cylindrical bone defects in sheep. The in vivo study was performed to assess the biocompatibility and bone remodeling of four cement formulations. After time periods of 2, 4, and 6 months, the cement samples were clinically and histologically evaluated. Histomorphometrically, the amount of new bone formation, fibrous tissue, and bone marrow and the area of remaining cement were measured. In all specimens, no signs of inflammation were detectable either macroscopically or microscopically. Cements differed mainly in their resorption time. Calcium sulfate was already completely resorbed at 2 months and showed a variable amount of new bone formation and/or fibrous tissue in the original drill hole over all time periods. The two DCPD cements in contrast were degraded to a large amount at 6 months, whereas the apatite was almost unchanged over all time periods. Copyright © 2013. Published by Elsevier B.V.

  8. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Alexandre Kaempfen

    2015-06-01

    Full Text Available The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step or only after six weeks of subcutaneous “incubation” (2-step. After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

  9. Time-lapse reveals that osteoclasts can move across the bone surface while resorbing

    DEFF Research Database (Denmark)

    Søe, Kent; Delaissé, Jean-Marie

    2017-01-01

    , clear real-time observations are still lacking. Herein, we used specific markers and time-lapse to monitor live the spatiotemporal generation of resorption events by osteoclasts cultured on bone slices. In accordance with the current view, we found alternating episodes of resorption and migration...... trenches. Compared to pit events, trench events show properties enabling higher aggressiveness: long duration (days), high erosion speed (two times faster) and long-distance erosion (several 100 µm). Simultaneous resorption and migration reflect a unique situation where epithelial/secretory and mesenchymal....../migratory characteristics are integrated into just one cell phenotype, and deserves attention in future research....

  10. The Macrophage Inflammatory Proteins MIP1α (CCL3 and MIP2α (CXCL2 in Implant-Associated Osteomyelitis: Linking Inflammation to Bone Degradation

    Directory of Open Access Journals (Sweden)

    Ulrike Dapunt

    2014-01-01

    Full Text Available Bacterial infections of bones remain a serious complication of endoprosthetic surgery. These infections are difficult to treat, because many bacterial species form biofilms on implants, which are relatively resistant towards antibiotics. Bacterial biofilms elicit a progressive local inflammatory response, resulting in tissue damage and bone degradation. In the majority of patients, replacement of the prosthesis is required. To address the question of how the local inflammatory response is linked to bone degradation, tissue samples were taken during surgery and gene expression of the macrophage inflammatory proteins MIP1α (CCL3 and MIP2α (CXCL2 was assessed by quantitative RT-PCR. MIPs were expressed predominantly at osteolytic sites, in close correlation with CD14 which was used as marker for monocytes/macrophages. Colocalisation of MIPs with monocytic cells could be confirmed by histology. In vitro experiments revealed that, aside from monocytic cells, also osteoblasts were capable of MIP production when stimulated with bacteria; moreover, CCL3 induced the differentiation of monocytes to osteoclasts. In conclusion, the multifunctional chemokines CCL3 and CXCL2 are produced locally in response to bacterial infection of bones. In addition to their well described chemokine activity, these cytokines can induce generation of bone resorbing osteoclasts, thus providing a link between bacterial infection and osteolysis.

  11. Bio resorbability of the modified hydroxyapatite in Tris-HCL buffer

    International Nuclear Information System (INIS)

    Golovanova, O A; Izmailov, R R; Ghyngazov, S A

    2016-01-01

    The solubility of carbonated hydroxyapatite powders and granulated carbonated hydroxyapatite produced from the synovial biofluid model solution has been studied. The kinetic characteristics of dissolution were determined. It was found that the solubility of carbonated hydroxyapatite is higher as compared to that of hydroxyapatite. The impact of the organic matrix on the rate of sample dissolution was revealed. For HA-gelatin composites, as the gelatin concentration grows, the dissolution rate becomes greater, and a sample of 6.0 g / L concentration has higher resorbability. The results of the research can be used to study the kinetics of dissolution and the biocompatibility of ceramic materials for medicine, namely for reconstructive surgery, dentistry, and development of drug delivery systems. (paper)

  12. Investigations of 90 SR activity concentrations in animal bones in Croatia

    Energy Technology Data Exchange (ETDEWEB)

    Maracic, M.; Franic, Z.; Marovic, G. [Institute for Medical Research and Occupational Health, Zagreb (Croatia)

    2006-07-01

    The paper describes investigations of 90 Sr activity concentrations in long bones of some domestic animals (cows, pigs and lambs) collected over the last ten years in the Republic of Croatia. These investigations are a part of an extended and still ongoing monitoring programme of radioactive contamination of human environment in Croatia. Bone is a critical organ for the accumulation of many radionuclides, including 90 Sr, a highly toxic radionuclide, similar to calcium in its chemicalaviour and metabolic processes. It has been found that the 90 Sr activity concentrations in bones differ between respective animal species, the highest activity concentrations being found in lamb bones. As the decrease of activity concentrations can be generally described by the exponential function, by fitting the measured data to the theoretical curve was estimated the ecological half-life of 90 Sr in bones of respective species. In addition was investigated the relation between 90 Sr activity concentrations in bones and fallout. The transient increases and decreases in 90 Sr activity concentrations in bones can be partially explained by a variety of environmental physical factors that naturally fluctuate. (authors)

  13. Investigations of 90 SR activity concentrations in animal bones in Croatia

    International Nuclear Information System (INIS)

    Maracic, M.; Franic, Z.; Marovic, G.

    2006-01-01

    The paper describes investigations of 90 Sr activity concentrations in long bones of some domestic animals (cows, pigs and lambs) collected over the last ten years in the Republic of Croatia. These investigations are a part of an extended and still ongoing monitoring programme of radioactive contamination of human environment in Croatia. Bone is a critical organ for the accumulation of many radionuclides, including 90 Sr, a highly toxic radionuclide, similar to calcium in its chemical behaviour and metabolic processes. It has been found that the 90 Sr activity concentrations in bones differ between respective animal species, the highest activity concentrations being found in lamb bones. As the decrease of activity concentrations can be generally described by the exponential function, by fitting the measured data to the theoretical curve was estimated the ecological half-life of 90 Sr in bones of respective species. In addition was investigated the relation between 90 Sr activity concentrations in bones and fallout. The transient increases and decreases in 90 Sr activity concentrations in bones can be partially explained by a variety of environmental physical factors that naturally fluctuate. (authors)

  14. Comparison of parameters of bone profile and homocysteine in physically active and non-active postmenopausal females.

    Science.gov (United States)

    Tariq, Sundus; Lone, Khalid Parvez; Tariq, Saba

    2016-01-01

    Optimal physical activity is important in attaining a peak bone mass. Physically active women have better bone mineral density and reduce fracture risk as compared to females living a sedentary life. The objective of this study was to compare parameters of bone profile and serum homocysteine levels in physically active and non-active postmenopausal females. In this cross sectional study postmenopausal females between 50-70 years of age were recruited and divided into two groups: Physically inactive (n=133) performing light physical activity and Physically active (n=34) performing moderate physical activity. Physical activity (in metabolic equivalents), bone mineral density and serum homocysteine levels were assessed. Spearman's rho correlation was applied to observe correlations. Two independent sample t test and Mann Whitney U test were applied to compare groups. P-value ≤ 0.05 was taken statistically significant. Parameters of bone profile were significantly higher and serum homocysteine levels were significantly lower in postmenopausal females performing moderate physical activity as compared to females performing light physical activity. Homocysteine was not significantly related to T-score and Z-score in both groups. Improving physical activity could be beneficial for improving the quality of bone, decreasing fracture risk and decreasing serum homocysteine levels.

  15. Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Wang, L.; Fan, J.; Lin, Y. S.

    2015-01-01

    Glucocorticoidinduced osteoporosis (GIOP) is a widespread clinical complication following glucocorticoid therapy. This irreversible damage to boneforming and resorbing cells is essential in the pathogenesis of osteoporosis. Autophagy is a physiological process involved in the regulation of cells...... and their responses to diverse stimuli, however, the role of autophagy in glucocorticoidinduced damage to bone marrow mesenchymal stem cells (BMSCs) remains unclear. The current study confirmed that glucocorticoid administration impaired the proliferation of BMSCs. Transmission electron microscopy...... that in response to glucocorticoid administration, induced autophagy aids to maintain proliferation and prevent apoptosis of BMSCs. Thus, it is hypothesized that autophagy may be a novel target in the treatment or prevention of osteoporosis....

  16. Ordinary and Activated Bone Grafts: Applied Classification and the Main Features

    Directory of Open Access Journals (Sweden)

    R. V. Deev

    2015-01-01

    Full Text Available Bone grafts are medical devices that are in high demand in clinical practice for substitution of bone defects and recovery of atrophic bone regions. Based on the analysis of the modern groups of bone grafts, the particularities of their composition, the mechanisms of their biological effects, and their therapeutic indications, applicable classification was proposed that separates the bone substitutes into “ordinary” and “activated.” The main differential criterion is the presence of biologically active components in the material that are standardized by qualitative and quantitative parameters: growth factors, cells, or gene constructions encoding growth factors. The pronounced osteoinductive and (or osteogenic properties of activated osteoplastic materials allow drawing upon their efficacy in the substitution of large bone defects.

  17. Human histologic evaluation of anorganic bovine bone mineral combined with recombinant human platelet-derived growth factor BB in maxillary sinus augmentation: case series study.

    Science.gov (United States)

    Nevins, Myron; Garber, David; Hanratty, James J; McAllister, Bradley S; Nevins, Marc L; Salama, Maurice; Schupbach, Peter; Wallace, Steven; Bernstein, Simon M; Kim, David M

    2009-12-01

    The objective of this proof-of-principle study was to examine the potential for improved bone regenerative outcomes in maxillary sinus augmentation procedures when recombinant human platelet-derived growth factor BB (0.3 mg/mL) is combined with particulate anorganic bovine bone mineral. The surgical outcomes in all treated sites were uneventful at 6 to 8 months, with sufficient regenerated bone present to allow successful placement of maxillary posterior implants. Large areas of dense, well-formed lamellar bone were seen throughout the intact core specimens in more than half of the grafted sites. Abundant numbers of osteoblasts were noted in concert with significant osteoid in all sites, indicating ongoing osteogenesis. A number of cores demonstrated efficient replacement of the normally slowly resorbing anorganic bovine bone mineral matrix particles with newly formed bone when the matrix was saturated with recombinant human platelet-derived growth factor BB.

  18. Bone regeneration with biomaterials and active molecules delivery.

    Science.gov (United States)

    D' Este, Matteo; Eglin, David; Alini, Mauro; Kyllonen, Laura

    2015-01-01

    The combination of biomaterials and drug delivery strategies is a promising avenue towards improved synthetic bone substitutes. With the delivery of active species biomaterials can be provided with the bioactivity they still lack for improved bone regeneration. Recently, a lot of research efforts have been put towards this direction. Biomaterials for bone regeneration have been supplemented with small or biological molecules for improved osteoprogenitor cell recruitment, osteoinductivity, anabolic or angiogenic response, regulation of bone metabolism and others. The scope of this review is to summarize the most recent results in this field.

  19. Clinical aspects of a multicenter clinical trial of implant-retained mandibular overdentures in patients with severely resorbed mandibles

    NARCIS (Netherlands)

    Geertman, ME; Boerrigter, EM; VanWaas, MAJ; vanOort, RP

    In a multicenter clinical trial treatment, the effects of overdentures on different implant systems in patients with severely resorbed mandibles were compared 1 year after the insertion of new dentures. The implant systems used were the transmandibular implant (TMI), the IMZ (IMZ), and the Branemark

  20. Instrumental neutron activation analysis of rib bone samples and of bone reference materials

    International Nuclear Information System (INIS)

    Saiki, M.; Takata, M.K.; Kramarski, S.; Borelli, A.

    2000-01-01

    The instrumental neutron activation analysis method was used for the determination of trace elements in rib bone samples taken from autopsies of accident victims. The elements Br, Ca, Cl, Cr, Fe, Mg, Mn, Na, P, Sr, Rb and Zn were determined in cortical tissues by using short and long irradiations with thermal neutron flux of the IEA-R1m nuclear reactor. The reference materials NIST SRM 1400 Bone Ash and NIST SRM 1486 Bone Meal were also analyzed in order to evaluate the precision and the accuracy of the results. It was verified that lyophilization is the most convenient process for drying bone samples since it does not cause any element losses. Comparisons were made between the results obtained for rib samples and the literature values as well as between the results obtained for different ribs from a single individual and for bones from different individuals. (author)

  1. Isotopic evidence for resorption of soft tissues and bone in immobilized dogs

    International Nuclear Information System (INIS)

    Klein, L.; Player, J.S.; Heiple, K.G.; Bahniuk, E.; Goldberg, V.M.

    1982-01-01

    Various experimental methods for producing bone and ligament atrophy have yielded contradictory results. These methods include denervation, immobilization (both internal and external), and disarticulation. We studied a model of internal skeletal fixation for twelve weeks in dogs that were chronically prelabeled with 3H-tetracycline, 45Ca, and 3H-proline. Bone resorption was analyzed by the loss of 3H-tetracycline, and bone and soft-tissue mass were analyzed by the radiochemical and chemical analysis of calcium and collagen. The strength of the anterior cruciate ligament was studied in tension to failure when a fast rate of deformation was applied. Failure of the femur-ligament-tibia complex occurred through the insertion of the ligament into the tibia for both the experimental and the control limbs. Loss of collagen was greater in the tibia and femur than in the lateral meniscus and anterior cruciate ligament, and correlated with a mechanical failure via bone. No evidence for collagen replacement in atrophied tissues was found, but one-half of the resorbed calcium was conserved. The marked loss of 3H-tetracycline indicated that bone atrophy was the result of increased resorption of bone rather than decreased bone formation. Clinical Relevance: We have demonstrated significant atrophy of the soft tissues (lateral meniscus and anterior cruciate ligament) as well as of bone in immobilized joints of dogs. It is likely that the decrease in strength of the bone-ligament-bone complex is related to this atrophy of soft tissues and bone around the joint

  2. Comparison of parameters of bone profile and homocysteine in physically active and non-active postmenopausal females

    OpenAIRE

    Tariq, Sundus; Lone, Khalid Parvez; Tariq, Saba

    2016-01-01

    Background and objectives: Optimal physical activity is important in attaining a peak bone mass. Physically active women have better bone mineral density and reduce fracture risk as compared to females living a sedentary life. The objective of this study was to compare parameters of bone profile and serum homocysteine levels in physically active and non-active postmenopausal females. Methods: In this cross sectional study postmenopausal females between 50-70 years of age were recruited and di...

  3. Five-year clinical and functional multislice computed tomography angiographic results after coronary implantation of the fully resorbable polymeric everolimus-eluting scaffold in patients with de novo coronary artery disease

    DEFF Research Database (Denmark)

    Onuma, Yoshinobu; Dudek, Dariusz; Thuesen, Leif

    2013-01-01

    This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California).......This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California)....

  4. Evaluation of the Fatigue Performance and Degradability of Resorbable PLDLLA-TMC Osteofixations

    Science.gov (United States)

    Landes, Constantin; Ballon, Alexander; Ghanaati, Shahram; Ebel, Daniel; Ulrich, Dieter; Spohn, Uwe; Heunemann, Ute; Sader, Robert; Jaeger, Raimund

    2013-01-01

    The fatigue performance of explanted in-situ degraded osteofixations/osteosyntheses, fabricated from poly (70L-lactide-co-24DL-lactide-6-trimethylane-carbonate or PLDLLA-TMC) copolymer was compared to that of virgin products. The fatigue test was performed on 21 explants retrieved from 12 women and 6 men; 16-46 years by a custom-designed three-point bend apparatus using a staircase method and a specified failure criterion (an increase of the deflection of the specimen > 1 mm) with run-out designated as “no failure” after 150,000 loading cycles. While all the virgin products showed run-out at 38N, all of the specimens fabricated from explants failed at this load level. For the explant specimens, although there was a trend of decreased failure load with increased in-situ time, this decrease was pronounced after 4 months in-situ, however, not yet statistically significant, while a 6-month in-situ explant had significantly less failure load. Three and four month in-situ explants had highly significant differences in failure load between measurements close and distant to the osteotomy line: p=0.0017 (the region of maximum load in-situ). In the virgin products, there were only traces of melt joining and cooling, left from a stage in the manufacturing process. For the implants retrieved after 4.5 months in-situ, the fracture surfaces showed signs of degradation of the implants, possibly caused by hydrolysis, and for those retrieved after 9 months in-situ, there were cracks and pores. Thus, the morphological results are consistent with those obtained in the fatigue test. The present results suggest that resorbable osteofixations fabricated from PLDLLA-TMC are stable enough to allow loading of the healing bone and degrade reliably PMID:24363786

  5. Physical activity, but not sedentary time, influences bone strength in late adolescence.

    Science.gov (United States)

    Tan, Vina Ps; Macdonald, Heather M; Gabel, Leigh; McKay, Heather A

    2018-03-20

    Physical activity is essential for optimal bone strength accrual, but we know little about interactions between physical activity, sedentary time, and bone outcomes in older adolescents. Physical activity (by accelerometer and self-report) positively predicted bone strength and the distal and midshaft tibia in 15-year-old boys and girls. Lean body mass mediated the relationship between physical activity and bone strength in adolescents. To examine the influence of physical activity (PA) and sedentary time on bone strength, structure, and density in older adolescents. We used peripheral quantitative computed tomography to estimate bone strength at the distal tibia (8% site; bone strength index, BSI) and tibial midshaft (50% site; polar strength strain index, SSI p ) in adolescent boys (n = 86; 15.3 ± 0.4 years) and girls (n = 106; 15.3 ± 0.4 years). Using accelerometers (GT1M, Actigraph), we measured moderate-to-vigorous PA (MVPA Accel ), vigorous PA (VPA Accel ), and sedentary time in addition to self-reported MVPA (MVPA PAQ-A ) and impact PA (ImpactPA PAQ-A ). We examined relations between PA and sedentary time and bone outcomes, adjusting for ethnicity, maturity, tibial length, and total body lean mass. At the distal tibia, MVPA Accel and VPA Accel positively predicted BSI (explained 6-7% of the variance, p accounting for lean mass. Sedentary time did not independently predict bone strength at either site. Greater tibial bone strength in active adolescents is mediated, in part, by lean mass. Despite spending most of their day in sedentary pursuits, adolescents' bone strength was not negatively influenced by sedentary time.

  6. Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation

    Directory of Open Access Journals (Sweden)

    Ghanaati Shahram

    2013-01-01

    Full Text Available Abstract Background Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods One gram each of either a porous beta-tricalcium phosphate (β-TCP or an hydroxyapatite/silicon dioxide (HA/SiO2-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting.

  7. The intensity of physical activity influences bone mineral accrual in childhood

    DEFF Research Database (Denmark)

    Heidemann, Malene Søborg; Mølgaard, Christian; Husby, Steffen

    2013-01-01

    Background Studies indicate genetic and lifestyle factors can contribute to optimal bone development. In particular, the intensity level of physical activity may have an impact on bone health. This study aims to assess the relationship between physical activity at different intensities and Bone....... Physical activity (PA) was recorded by accelerometers (ActiGraph, model GT3X). Percentages of different PA intensity levels were calculated and log odds of two intensity levels of activity relative to the third level were calculated. Multilevel regression analyses were used to assess the relationship...... between the categories of physical activity and bone traits. Results Of 800 invited children, 742 (93%) accepted to participate. Of these, 682/742 (92%) participated at follow up. Complete datasets were obtained in 602/742 (81%) children. Mean (range) of age was 11.5 years (9.7-13.9). PA at different...

  8. 3D Powder Printed Bioglass and β-Tricalcium Phosphate Bone Scaffolds

    Directory of Open Access Journals (Sweden)

    Michael Seidenstuecker

    2017-12-01

    Full Text Available The use of both bioglass (BG and β tricalcium phosphate (β-TCP for bone replacement applications has been studied extensively due to the materials’ high biocompatibility and ability to resorb when implanted in the body. 3D printing has been explored as a fast and versatile technique for the fabrication of porous bone scaffolds. This project investigates the effects of using different combinations of a composite BG and β-TCP powder for 3D printing of porous bone scaffolds. Porous 3D powder printed bone scaffolds of BG, β-TCP, 50/50 BG/β-TCP and 70/30 BG/β-TCP compositions were subject to a variety of characterization and biocompatibility tests. The porosity characteristics, surface roughness, mechanical strength, viability for cell proliferation, material cytotoxicity and in vitro bioactivity were assessed. The results show that the scaffolds can support osteoblast-like MG-63 cells growth both on the surface of and within the scaffold material and do not show alarming cytotoxicity; the porosity and surface characteristics of the scaffolds are appropriate. Of the two tested composite materials, the 70/30 BG/β-TCP scaffold proved to be superior in terms of biocompatibility and mechanical strength. The mechanical strength of the scaffolds makes them unsuitable for load bearing applications. However, they can be useful for other applications such as bone fillers.

  9. Active Bone Conduction Prosthesis: BonebridgeTM

    Directory of Open Access Journals (Sweden)

    Zernotti, Mario E.

    2015-10-01

    Full Text Available Introduction Bone conduction implants are indicated for patients with conductive and mixed hearing loss, as well as for patients with single-sided deafness (SSD. The transcutaneous technology avoids several complications of the percutaneous bone conduction implants including skin reaction, skin growth over the abutment, and wound infection. The Bonebridge (MED-EL, Austria prosthesis is a semi-implantable hearing system: the BCI (Bone Conduction Implant is the implantable part that contains the Bone Conduction-Floating Mass Transducer (BC-FMT, which applies the vibrations directly to the bone; the external component is the audio processor Amadé BB (MED-EL, Austria, which digitally processes the sound and sends the information through the coil to the internal part. Bonebridge may be implanted through three different approaches: the transmastoid, the retrosigmoid, or the middle fossa approach. Objective This systematic review aims to describe the world́s first active bone conduction implant system, Bonebridge, as well as describe the surgical techniques in the three possible approaches, showing results from implant centers in the world in terms of functional gain, speech reception thresholds and word recognition scores. Data Synthesis The authors searched the MEDLINE database using the key term Bonebridge. They selected only five publications to include in this systematic review. The review analyzes 20 patients that received Bonebridge implants with different approaches and pathologies. Conclusion Bonebridge is a solution for patients with conductive/mixed hearing loss and SSD with different surgical approaches, depending on their anatomy. The system imparts fewer complications than percutaneous bone conduction implants and shows proven benefits in speech discrimination and functional gain.

  10. Amylin(1-8) is devoid of anabolic activity in bone

    DEFF Research Database (Denmark)

    Ellegaard, Maria; Thorkildsen, Christian; Vibe-Petersen, Solveig

    2010-01-01

    Amylin(1-8), a cyclic peptide consisting of the eight N-terminal amino acids of the 37-amino acid peptide amylin, has been shown to induce proliferation of primary osteoblasts and to induce bone formation in healthy male mice, whereas no data on efficacy in bone disease-related models have been r......, our results indicate that amylin(1-8) does not show agonist activity on amylin receptors, does not affect osteoblast proliferation, and is devoid of anabolic activity in bone....

  11. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

    Science.gov (United States)

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

  12. Combined use of bone and bone marrow scintigraphies for the diagnosis of active sacroiliitis. A new approach

    Energy Technology Data Exchange (ETDEWEB)

    Bozkurt, M.F.; Ugur, O.; Ertenli, I.; Caner, B. [Hacettepe Univ., Ankara (Turkey). Faculty of Medicine

    2001-04-01

    Diagnosis of sacroiliitis (SI) with bone scintigraphy may involve difficulties even with a quantitative approach. The aim of this study was to evaluate the combined use of bone and bone marrow scintigraphies for the diagnosis of active sacroiliitis. Thirty-one patients who were clinically suspected to have SI were included in the study. Bone and marrow scintigraphies were done after injections of 740 MBq of {sup 99m}Tc-MDP (MDP) and 370 MBq of {sup 99m}Tc-sulfur colloid (SC) respectively with a 2-day interval. Both visual and quantitative assessment of MDP uptake and visual assessment of SC uptake in sacroiliac joints were performed. Also sacroiliac joint radiographic findings for each patient were evaluated and graded from 0 to 4 according to the New York grading system. Patients were divided into 2 groups according to their x-ray findings (Group A: grade 0-2, Group B: grade 3-4). A total of 14 patients (10 bilateral, 4 unilateral) had increased MDP uptake with decreased/normal SC uptake. Twelve of 14 patients had grade 0-2 radiographic changes while only 2 patients had grade 3-4 radiographic changes. Increased MDP uptake with decreased/normal SC uptake is the most common scintigraphic pattern seen in acute phase SI in which radiographic findings are generally found to be normal or slightly changed. In at least in 8 patients the decreased bone marrow uptake of SC was demonstrated, supporting the diagnosis. Although our results did not reveal any significant superiority of bone marrow scintigraphy to bone scan for the detection of active sacroiliitis, combined use of bone and bone marrow scintigraphies was presented as an alternative method to characterize patients with active sacroiliitis. (author)

  13. BONE MINERAL DENSITY IN PHYSICALLY ACTIVE WOMEN ASSESSED BY ULTRASOUND DESINTOMETRY

    Directory of Open Access Journals (Sweden)

    Ana Marijanac

    2015-05-01

    Full Text Available Osteoporosis is a disease characterized by low bone mass and density. Physical activity has a positive effect on bone tissue, and it is recommended to prevent bone loss which comes with age. Methods: In purpose of determining bone mineral density in women who are physically active we examined 35 women divided into two groups – subjects who are premenopausal (n=20, 43.52 ± 7.56 years, and subjects who are postmenopausal (n=15, 55.89 ± 5.48. The subjects exercised Pilates method twice a week for one hour. Bone mineral density measurements were done by ultrasound densitometer „Sahara“ through the calcaneus. We get the data of the estimated bone density and T-score for right and left foot separate. Results: According to results premenopausal women have normal bone density, and postmenopausal values represent osteopenia, according to the WHO. There is no subjects who established osteoporosis. Discussion: Previous investigations have confirmed that physical activity is important for the preservation of the bone quality. Increasing steps, using simple everyday tasks, can prevent decrease in BMD in postmenopausal women (Muir et al., 2013, Ashe et al, 2008. There’s difference in the density of the calcaneus between physically active and those who are not, measured by ultrasound densitometry (Vainionpää et al, 2005. We use quantitative ultrasound densitometry to describe BMI of women who exercise Pilates and support the finding that physical activity is one of the ways that may prevent the BMD loss. These research was done as a part of long-term project entitled „Impact of physical activity of the working population“ which is co-financed by Provincial Secretariat for Science and Technological Development.

  14. TRAF family member-associated NF-κB activator (TANK) induced by RANKL negatively regulates osteoclasts survival and function.

    Science.gov (United States)

    Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

    2012-01-01

    Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and confirmed by western blot and quantitative RT-PCR. Bone marrow macrophages (BMMs) transduced with lentivirus carrying tank-shRNA were induced to form osteoclast in the presence of RANKL and M-CSF. Tank expression was downregulated by 90% by Tank-shRNA, which is confirmed by western blot. Compared with wild-type (WT) cells, osteoclastogenesis of Tank-silenced BMMs was increased, according to tartrate-resistant acid phosphatase (TRAP) stain on day 5 and day 7. Number of bone resorption pits by Tank-silenced osteoclasts was increased by 176% compared with WT cells, as shown by wheat germ agglutinin (WGA) stain and scanning electronic microscope (SEM) analysis. Survival rate of Tank-silenced mature osteoclast is also increased. However, acid production of Tank-knockdown cells was not changed compared with control cells. IκBα phosphorylation is increased in tank-silenced cells, indicating that TANK may negatively regulate NF-κB activity in osteoclast. In conclusion, Tank, whose expression is increased during osteoclastogenesis, inhibits osteoclast formation, activity and survival, by regulating NF-κB activity and c-FLIP expression. Tank enrolls itself in a negative feedback loop in bone resorption. These results may provide means for therapeutic intervention in diseases of excessive bone resorption.

  15. Fixation of fractures of the condylar head of the mandible with a new magnesium-alloy biodegradable cannulated headless bone screw.

    Science.gov (United States)

    Leonhardt, H; Franke, A; McLeod, N M H; Lauer, G; Nowak, A

    2017-07-01

    It is difficult to fix fractures of the condylar head of the mandible. Several techniques have been described which show satisfactory outcomes, but stability can be questionable, and some can cause irritation of the soft tissues. We describe a technique and first results of treating such fractures with resorbable magnesium-based headless bone screws (Magnezix ® 2.7mm CS; Syntellix AG, Hanover, Germany). Copyright © 2017 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  16. Transosseous fixation of pediatric displaced mandibular fractures with polyglactin resorbable suture--a simplified technique.

    Science.gov (United States)

    Chandan, Sanjay; Halli, Rajshekhar; Joshi, Samir; Chhabaria, Gaurav; Setiya, Sneha

    2013-11-01

    Management of pediatric mandibular fractures presents a unique challenge to surgeons in terms of its numerous variations compared to adults. Both conservative and open methods have been advocated with their obvious limitations and complications. However, conservative modalities may not be possible in grossly displaced fractures, which necessitate the open method of fixation. We present a novel and simplified technique of transosseous fixation of displaced pediatric mandibular fractures with polyglactin resorbable suture, which provides adequate stability without any interference with tooth buds and which is easy to master.

  17. Evaluation of 99mTc-MDP bone imaging in monitoring the muscle-pedicle bone graft osteogenic activation

    International Nuclear Information System (INIS)

    Sang Shibiao; Wu Yiwei; Zhang Wei; Jiang Yimin; Chen Guangxiang; Dong Tianhua

    2002-01-01

    Nine mature and healthy dogs were divided into 4 groups randomly. The first group consists of 3 dogs, and the rest groups, 2 dogs. Self-control way was used. The left ilium was the experimental site, where the bone piece with sartorial muscle attached was cut from ilium. The right side served as control, where the graft bone from ilium was wrapped up with silica gel, then fixed subcutaneously. The pedicled bone pieces were retrieved in 2, 4, 6, 8 weeks after surgery, the size of graft bones from two sides were the same. Survival range, osteogenic formation of muscle-pedicle bone were examined by 99m Tc-MDP bone imaging and histological method to evaluate the clinical value of treatment of ischemic osteonecrosis of the femoral head with muscle-pedicle bone grafting. The results were as follows: 1. The part of bone attached by the sartorial survived, but osteonecrosis was observed at the location of 1.2-1.7 cm from attached point of muscle. 2. There were two forms observed in the course of osteogenic activation of muscle-pedicle bone. Under the reduction of mechanical stimulation and blood supply, bone marrow tissue was replaced by fibro-granulation tissue and new capillary in the survival part, while the survival bone of proximal part grew distally and gradually replace the dead bone of distal part. 3. Histological examination revealed that small amounts of fibro-granulation tissue and new capillary appeared in 2nd week, primary trabeculae appeared in 6th week, and in 8th week, some trabeculae recovered their normal appearance and osteogenic cell reduced remarkably. 4. Survival range of muscle-pedicle graft bone was directly proportional to the width of muscle pedicle. Therefore, radionuclide bone imaging and histological examination demonstrated that muscle-pedicle graft bone was a piece of bone with relatively poor blood supply, its effect is repairing necrosis and collapse of the femoral head is limited. 99m Tc-MDP bone imaging may be an effective and first

  18. Three Phase Bone Scintigraphy in Active and Inactive Osteomyelitis

    International Nuclear Information System (INIS)

    Yang, Woo Jin; Chung, Soo Kyo; Ha, Hyun Kwon; Bahk, Yong Whee

    1988-01-01

    To Appreciate the value of bone scintigraphy in determination of the bony infection, we performed three phase bone scintigraphy in 34 cases of osteomyelitis of extremities prospectively. They were clinically inactive in 11 and active in 23 cases. We confirmed the active osteomyelitis by operation or aspiration within one week after scintigraphy. Perfusion, blood pool and delayed images were analyzed respectively and compared with the plain roentgenograms. All 23 active lesions showed diffusely increased perfusion in affected limbs. The areas of the increased activities on blood pool images were larger than or similar to those on delayed images in 17 cases (73.9%) with active osteomyelitis and smaller in 6 cases (26.1%). 5 of the latter 6 cases showed definite soft tissue activities on blood pool images. In inactive cases bone scintigrams were completely normal in 4 cases. Two of those were normal on plain films and remaining two showed mild focal bony sclerosis. Among 7 inactive lesions, perfusion was normal in 2 cases, diffusely increased in 4 cases and diffusely decreased in 1 case. 6 of these 7 cases showed increased activities both on blood pool and delayed images and the areas of increased activities on blood pool images didn't exceed those on delayed images. Bony sclerosis was noted on plain films in those 7 inactive lesions and the extent of the sclerosis correlated well to delayed images. Large blood pool activity was characteristics of active osteomyelitis. Normal three phase bone scintigram may indicate the time to terminate the treatment, but increased activity on perfusion and blood pool scans is not absolute indication of active lesion if the extent of the lesion on the blood pool image is smaller than that on delayed image and if no definite soft tissue activity is noted on perfusion and blood pool images in clinically inactive patient.

  19. Investigations of 90Sr Activity Concentrations in Animal Bones in Republic of Croatia

    International Nuclear Information System (INIS)

    Maracic, M.; Franic, Z.; Marovic, G.

    2008-01-01

    The paper presents investigations of 90Sr activity concentrations in long bones of some domestic animals (cows, pigs, lambs) collected over the last ten years in the Republic of Croatia. The investigations are a part of an extended and still ongoing monitoring programme of radioactive contamination of human environment of Croatia. Bone is critical organ for the accumulation of many radionuclides, including 90Sr, a highly toxic radionuclide, similar to calcium in its chemical behaviour and metabolic processes. It has been found that the 90Sr activity concentrations in bones differ between respective animal species, the highest activity concentrations being found in lamb bones in year 2005 (472.61 mBqgCa -1 or 2.14 Bqkg -1 ). In cow bones highest value being found was in 1998, being 611.42 mBqgCa -1 or 69.09 Bqkg -1 90Sr. The transient increases and decreases in 90Sr activity concentrations in bones can be partially explained by a variety of environmental physical and biochemical factors that naturally fluctuate. As the levels of stable strontium in bone tissue is strongly correlated to calcium content of bone, 90Sr can be used as efficient radiotracer of stable strontium, which is itself important since it positively affects bone metabolism promoting bone formation and decreasing bone resorption, leading to normalized bone density.(author)

  20. miR-218 is involved in the negative regulation of osteoclastogenesis and bone resorption by partial suppression of p38MAPK-c-Fos-NFATc1 signaling: Potential role for osteopenic diseases.

    Science.gov (United States)

    Qu, Bo; Xia, Xun; Yan, Ming; Gong, Kai; Deng, Shaolin; Huang, Gang; Ma, Zehui; Pan, Xianming

    2015-10-15

    The increased osteoclastic activity accounts for pathological bone loss in diseases including osteoporosis. MicroRNAs are widely accepted to be involved in the regulation of osteopenic diseases. Recently, the low expression of miR-218 was demonstrated in CD14(+) peripheral blood mononuclear cells (PBMCs) from patients with postmenopausal osteoporosis. However, its role and the underlying mechanism in osteoporosis are still undefined. Here, an obvious decrease in miR-218 expression was observed during osteoclastogenesis under receptor activator of nuclear factor κB ligand (RANKL) stimulation, in both osteoclast precursors of bone marrow macrophages (BMMs) and RAW 264.7. Further analysis confirmed that overexpression of miR-218 obviously attenuated the formation of multinuclear mature osteoclasts, concomitant with the decrease in Trap and Cathepsin K levels, both the master regulators of osteoclastogenesis. Moreover, miR-218 up-regulation dramatically inhibited osteoclast precursor migration, actin ring formation and bone resorption. Mechanism assay demonstrated that miR-218 overexpression attenuated the expression of p38MAPK, c-Fos and NFATc1 signaling molecules. Following preconditioning with P79350, an agonist of p38MAPK, the inhibitor effect of miR-218 on osteoclastogenesis and bone-resorbing activity was strikingly ameliorated. Together, this study revealed a crucial role of miR-218 as a negative regulator for osteoclastogenesis and bone resorption by suppressing the p38MAPK-c-Fos-NFATc1 pathway. Accordingly, this research will provide a promising therapeutic agent against osteopenic diseases including osteoporosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. World’s First Clinical Case of Gene-Activated Bone Substitute Application

    Directory of Open Access Journals (Sweden)

    I. Y. Bozo

    2016-01-01

    Full Text Available Treatment of patients with large bone defects is a complex clinical problem. We have initiated the first clinical study of a gene-activated bone substitute composed of the collagen-hydroxyapatite scaffold and plasmid DNA encoding vascular endothelial growth factor. The first patient with two nonunions of previously reconstructed mandible was enrolled into the study. Scar tissues were excised; bone defects (5–14 mm between the mandibular fragments and nonvascularized rib-bone autograft were filled in with the gene-activated bone substitute. No adverse events were observed during 12 months of follow-up. In 3 months, the average density of newly formed tissues within the implantation zone was 402.21 ± 84.40 and 447.68 ± 106.75 HU in the frontal and distal regions, respectively, which correlated with the density of spongy bone. Complete distal bone defect repair with vestibular and lingual cortical plates formation was observed in 6 and 12 months after surgery; thereby the posterior nonunion was successfully eliminated. However, there was partial resorption of the proximal edge of the autograft entailed to relapse of the anterior nonunion. Thus, the first clinical data on the safety and efficacy of the gene-activated bone substitute were obtained. Given a high complexity of the clinical situation the treatment, results might be considered as promising. NCT02293031.

  2. Bone Response to Dietary Co-Enrichment with Powdered Whole Grape and Probiotics

    Directory of Open Access Journals (Sweden)

    Cynthia Blanton

    2018-01-01

    Full Text Available Nutrition is a primary modifiable determinant of chronic noncommunicable disease, including osteoporosis. An etiology of osteoporosis is the stimulation of bone-resorbing osteoclasts by reactive oxygen species (ROS. Dietary polyphenols and probiotics demonstrate protective effects on bone that are associated with reduced ROS formation and suppressed osteoclast activity. This study tested the effect of dietary enrichment with powdered whole grape and probiotics (composed of equal parts Bifidobacterium bifidum, B. breve, Lactobacillus casei, L. plantarum, and L. bulgaricus on bone microarchitecture in a mouse model of age-related osteoporosis. Groups (n = 7 each of 10-month-old male mice were fed one of six diets for 6 months: 10% grape powder with sugar corrected to 20%; 20% grape powder; 1% probiotic with sugar corrected to 20%; 10% grape powder + 1% probiotic with sugar corrected to 20%; 20% grape powder + 1% probiotic; 20% sugar control. Femur, tibia and 4th lumbar vertebrae from 10-month-old mice served as comparator baseline samples. Bone microarchitecture was measured by micro-computed tomography and compared across diet groups using analysis of variance. Aging exerted a significant effect on tibia metaphysis trabecular bone, with baseline 10-month-old mice having significantly higher bone volume/total volume (BV/TV and trabecular number measurements and lower trabecular spacing measurements than all 16-month-old groups (p < 0.001. Neither grape nor probiotic enrichment significantly improved bone microarchitecture during aging compared to control diet. The combination of 20% grape + 1% probiotic exerted detrimental effects on tibia metaphysis BV/TV compared to 10% grape + 1% probiotic, and trabecular number and trabecular spacing compared to 10% grape + 1% probiotic, 1% probiotic and control groups (p < 0.05. Femur metaphysis trabecular bone displayed less pronounced aging effects than tibia bone, but also showed detrimental effects of the

  3. Human brain activity associated with painful mechanical stimulation to muscle and bone.

    Science.gov (United States)

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-08-01

    The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.

  4. A visco-poroelastic model of functional adaptation in bones reconstructed with bio-resorbable materials.

    Science.gov (United States)

    Giorgio, Ivan; Andreaus, Ugo; Scerrato, Daria; dell'Isola, Francesco

    2016-10-01

    In this paper, the phenomena of resorption and growth of bone tissue and resorption of the biomaterial inside a bicomponent system are studied by means of a numerical method based on finite elements. The material behavior is described by a poro-viscoelastic model with infiltrated voids. The mechanical stimulus that drives these processes is a linear combination of density of strain energy and viscous dissipation. The external excitation is represented by a bending load slowly variable with sinusoidal law characterized by different frequencies. Investigated aspects are the influence of the load frequency, of type of the stimulus and of the effective porosity on the time evolution of the mass densities of considered system.

  5. [Bone Cell Biology Assessed by Microscopic Approach. The effects of active vitamin D3 such as alfacalcidol and eldecalcitol on bone quality].

    Science.gov (United States)

    Saito, Mitsuru; Marumo, Keishi

    2015-10-01

    Active vitamin D3 is used for the treatment for osteoporosis in Japan. Recently, data have accumulated that collagen cross-link formation in bone affect bone strength. In fact, impaired enzymatic cross-linking, over-hydroxylation of crosslinks, and an increase in non-enzymatic crosslinking advanced glycation end products (AGEs) such as pentosidine, in bone collagen have been proposed as a major cause of bone fragility in osteoporosis. We reported that alfacalcidol and eldecalcitol improves bone material properties such as collagen cross-link formation, microarchitecture, and microcrack resulting in the increase of bone strength (Saito M, Bone 2010;46:1170-1179, Calcif Tissue Int 2011;88:314-324, Bone, 2015;73:8-15). In this review, we described how active vitamin D3 improve bone collagen cross-link formation and mineral qualities.

  6. A resorbable antibiotic-eluting polymer composite bone void filler for perioperative infection prevention in a rabbit radial defect model.

    Directory of Open Access Journals (Sweden)

    Benjamin D Brooks

    Full Text Available Nearly 1.3 million total joint replacement procedures are performed in the United States annually, with numbers projected to rise exponentially in the coming decades. Although finite infection rates for these procedures remain consistently low, device-related infections represent a significant cause of implant failure, requiring secondary or revision procedures. Revision procedures manifest several-fold higher infection recurrence rates. Importantly, many revision surgeries, infected or not, require bone void fillers to support the host bone and provide a sufficient tissue bed for new hardware placement. Antibiotic-eluting bone void fillers (ABVF, providing both osteoconductive and antimicrobial properties, represent one approach for reducing rates of orthopedic device-related infections. Using a solvent-free, molten-cast process, a polymer-controlled antibiotic-eluting calcium carbonate hydroxyapatite (HAP ceramic composite BVF (ABVF was fabricated, characterized, and evaluated in vivo using a bacterial challenge in a rabbit radial defect window model. ABVF loaded with tobramycin eliminated the infectious burden in rabbits challenged with a clinically relevant strain of Staphylococcus aureus (inoculum as high as 10⁷ CFU. Histological, microbiological, and radiographic methods were used to detail the effects of ABVF on microbial challenge to host bone after 8 weeks in vivo. In contrast to the HAP/BVF controls, which provided no antibiotic protection and required euthanasia 3 weeks post-operatively, tobramycin-releasing ABVF animals showed no signs of infection (clinical, microbiological, or radiographic when euthanized at the 8-week study endpoint. ABVF sites did exhibit fibrous encapsulation around the implant at 8 weeks. Local antibiotic release from ABVF to orthopedic sites requiring bone void fillers eliminated the periprosthetic bacterial challenge in this 8-week in vivo study, confirming previous in vitro results.

  7. NF-κB decoy oligodeoxynucleotide mitigates wear particle-associated bone loss in the murine continuous infusion model.

    Science.gov (United States)

    Lin, Tzu-Hua; Pajarinen, Jukka; Sato, Taishi; Loi, Florence; Fan, Changchun; Córdova, Luis A; Nabeshima, Akira; Gibon, Emmanuel; Zhang, Ruth; Yao, Zhenyu; Goodman, Stuart B

    2016-09-01

    Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Wear particle-induced chronic inflammation is associated with the development of periprosthetic osteolysis. Modulation of NF-κB signaling in macrophages, osteoclasts, and mesenchymal stem cells could potentially mitigate this disease. In the current study, we examined the effects of local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) on wear particle-induced bone loss in a murine continuous femoral particle infusion model. Ultra-high molecular weight polyethylene particles (UHMWPE) with or without lipopolysaccharide (LPS) were infused via osmotic pumps into hollow titanium rods placed in the distal femur of mice for 4weeks. Particle-induced bone loss was evaluated by μCT, and immunohistochemical analysis of sections from the femur. Particle infusion alone resulted in reduced bone mineral density and trabecular bone volume fraction in the distal femur. The decoy ODN reversed the particle-associated bone volume fraction loss around the implant, irrespective of the presence of LPS. Particle-infusion with LPS increased bone mineral density in the distal femur compared with particle-infusion alone. NF-κB decoy ODN reversed or further increased the bone mineral density in the femur (3-6mm from the distal end) exposed to particles alone or particles plus LPS. NF-κB decoy ODN also inhibited macrophage infiltration and osteoclast number, but had no significant effects on osteoblast numbers in femurs exposed to wear particles and LPS. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced osteolysis. Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Chronic inflammation is crucial for the development of wear particle-associated bone loss. Modulation of NF-κB signaling in macrophages (pro-inflammatory cells), osteoclasts (bone-resorbing

  8. Comparison of resorbable poly-L-lactic acid-polyglycolic acid and internal Palmaz stents for the surgical correction of severe tracheomalacia.

    Science.gov (United States)

    Sewall, Gregory K; Warner, Thomas; Connor, Nadine P; Hartig, Gregory K

    2003-06-01

    Tracheomalacia (TM) is associated with expiratory airway collapse and potentially fatal respiratory distress. Internal and external tracheal stents and, recently, resorbable biopolymers have been used to treat this condition. In this study, the efficacy and biocompatibility of internal Palmaz stents and external poly-L-lactic acid-polyglycolic acid (PLPG) stents were compared in a model of severe TM induced in piglets. The tracheas were repaired with one of two stenting methods, and the animals survived for up to 16 weeks. Weight gain, adverse respiratory signs and symptoms, tracheal or lung histopathologic changes, and internal and external tracheal diameters were measured. The animals in the PLPG group uniformly were free of respiratory distress and tracheal stenosis or inflammation, whereas all animals in the Palmaz group developed respiratory distress as a result of pneumonia or tracheal stenosis caused by intraluminal granulation tissue. In conclusion, superior efficacy of external, resorbable PLPG stents was found relative to internal Palmaz stents for the surgical repair of severe TM.

  9. Metals for bone implants. Part 1. Powder metallurgy and implant rendering.

    Science.gov (United States)

    Andani, Mohsen Taheri; Shayesteh Moghaddam, Narges; Haberland, Christoph; Dean, David; Miller, Michael J; Elahinia, Mohammad

    2014-10-01

    New metal alloys and metal fabrication strategies are likely to benefit future skeletal implant strategies. These metals and fabrication strategies were looked at from the point of view of standard-of-care implants for the mandible. These implants are used as part of the treatment for segmental resection due to oropharyngeal cancer, injury or correction of deformity due to pathology or congenital defect. The focus of this two-part review is the issues associated with the failure of existing mandibular implants that are due to mismatched material properties. Potential directions for future research are also studied. To mitigate these issues, the use of low-stiffness metallic alloys has been highlighted. To this end, the development, processing and biocompatibility of superelastic NiTi as well as resorbable magnesium-based alloys are discussed. Additionally, engineered porosity is reviewed as it can be an effective way of matching the stiffness of an implant with the surrounding tissue. These porosities and the overall geometry of the implant can be optimized for strain transduction and with a tailored stiffness profile. Rendering patient-specific, site-specific, morphology-specific and function-specific implants can now be achieved using these and other metals with bone-like material properties by additive manufacturing. The biocompatibility of implants prepared from superelastic and resorbable alloys is also reviewed. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. Physical activity and bone mineral density in Italian middle-aged women

    International Nuclear Information System (INIS)

    Bidoli, Ettore; Schinella, Domenico; Franceschi, Silvia

    1998-01-01

    Osteoporosis is a major health issue in postmenopausal women on account of the association between low bone mineral density and fractures. A role of physical activity in the prevention and treatment of low bone mineral density is possible but still unclear. The relationship between low spine bone mineral density measured by means of dual photon absorptiometry at lumbar spines, and levels of past and recent physical activity has been assessed by means of a population-based screening study carried out on 1373 women (age 40-64 years) in the North-East of Italy. Physical activity at work and in leisure time was investigated for three specific periods of life: at age 12, between 15 and 19 years (during bone formative years), and in the recent years prior to the interview (30-39 or 50-59 years). Data were analysed comparing low versus high bone mineral density tertile (i.e., 458 and 461 women, respectively), after controlling for other known contributory factors in the development of osteoporosis. A positive association emerged with leisure time physical activity, with significant trends at age 15-19 (odds ratio (OR) for low versus high tertile of leisure time activity: 1.4, 95% confidence interval (CI): 0.8-2.4) and at most recent age (OR: 1.7, 95% CI: 1.1-2.6). Risk trends with occupational physical activity were less clear and non-statistically significant. The present Southern European cross-sectional study lends further support to the possibility that past and recent physical activity helps increasing bone mineral density in middle-aged women. Although the most beneficial type and intensity level of exercise has yet to be determined, the present results provide further evidence that participation in even moderate exercise programs should be encouraged

  11. Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.

    Science.gov (United States)

    Karaca, Anara; Malladi, Vijayram Reddy; Zhu, Yan; Tafaj, Olta; Paltrinieri, Elena; Wu, Joy Y; He, Qing; Bastepe, Murat

    2018-05-01

    GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα R201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα R201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα R201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Gingival crevicular fluid bone turnover biomarkers: How postmenopausal women respond to orthodontic activation.

    Science.gov (United States)

    Smuthkochorn, Sorapan; Palomo, J Martin; Hans, Mark G; Jones, Corey S; Palomo, Leena

    2017-07-01

    Bone turnover associated with orthodontic tooth movement is evidenced by increased bone turnover markers in gingival crevicular fluid (GCF). Postmenopausal women have an increased concentration of serum bone turnover markers. The filtrate of this serum makes up GCF, but little is known of the bone turnover around teeth in this cohort. The objective of this investigation was to compare the GCF bone turnover markers in premenopausal vs postmenopausal women receiving orthodontic treatment at baseline and at orthodontic activation. Twenty-eight women were enrolled in the study and separated into 2 groups: premenopausal (16) and postmenopausal (12). Bone turnover was evaluated by GCF at baseline and 24 hours after orthodontic appliance activation. GCF concentrations of RANKL and OPN were measured using ELISA. Baseline and change in concentrations were compared between groups. Baseline RANKL and OPN were significantly different between the premenopausal and postmenopausal groups (P orthodontic appliance activation in both groups (P orthodontic activation was not significantly different between groups. Although postmenopausal women have a different bone turnover profile at baseline than do their premenopausal counterparts, there is no difference in their response to orthodontic activation. This confers a level of security associated with orthodontic activation. Future studies are warranted to construct biomarker curves throughout orthodontic therapy. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  13. Bone Scan in Detection of Biological Activity in Nonhypertrophic Fracture Nonunion

    OpenAIRE

    Gandhi, Sunny J.; Rabadiya, Bhavdeep

    2017-01-01

    Biological activity of the fracture site is very important factor in treatment planning of fracture nonunion. If no biological activity is detected, then an autologous bone graft can be supplemented or osteogenic supplementations, such as bone morphogenetic protein is given. If biological activity is present, then secure fixation is sufficient to achieve bony union. Biological activity of nonunions is usually assessed by conventional radiographs. The presence of callus formation is usually as...

  14. Xerogel Interfaced Nanofibers Stimulate Bone Regeneration Through the Activation of Integrin and Bone Morphogenetic Protein Pathways.

    Science.gov (United States)

    Lee, Yoo-Mi; Yun, Hyung-Mun; Lee, Hye-Young; Lim, Hyun-Chang; Lee, Hae-Hyoung; Kim, Hae-Won; Kim, Eun-Cheol

    2017-02-01

    A xerogel was interfaced onto biopolymer nanofibers though a core–shell electrospinning design for bone regeneration. The xerogel-interfaced biopolymer nanofibrous matrix was bioactive and highly hydrophilic, with a significant decrease in the water contact angle. The matrix showed excellent in vitro responses of primary osteoblasts in terms of adhesion, proliferation, and migration. Furthermore, the osteoblastic differentiation of cells, including alkaline phosphatase activity, mineralization, and gene expression, was significantly upregulated by the xerogel interface. In vivo animal tests in a critical-sized calvarial defect confirmed the new bone formation ability of the xerogel-surfaced nanofiber matrices. The underlying signaling mechanisms of the stimulation were implied to be integrin and bone morphogenetic protein (BMP) pathways, as demonstrated by the activation of integrin (α2β1) and downstream signaling molecules (FAK, paxillin, RhoA, MAPK, and NF-κB), as well as the BMPs and the downstream transcription factor Smad1/5/8. Taking these findings together, the xerogel-surfaced biopolymer nanofibers are proposed to be a promising scaffold candidate for bone regeneration.

  15. Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD.

    Science.gov (United States)

    Havill, Lorena M; Mahaney, Michael C; L Binkley, Teresa; Specker, Bonny L

    2007-05-01

    Quantitative genetic analyses of bone data for 710 inter-related individuals 8-85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific. Genetic and environmental factors play a complex role in determining BMC, bone size, and BMD. This study assessed the heritability of bone measures; characterized the effects of age, sex, and physical activity on bone; and tested for age- and sex-specific bone effects of activity. Measures of bone size and areal and volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on 710 related individuals (466 women) 8-85 yr of age. Measures of activity included percent time in moderate + vigorous activity (%ModVig), stair flights climbed per day, and miles walked per day. Quantitative genetic analyses were conducted to model the effects of activity and covariates on bone outcomes. Accounting for effects of age, sex, and activity levels, genes explained 40-62% of the residual variation in BMC and BMD and 27-75% in bone size (all pBMC and cross-sectional area (CSA) at the 4% radius, but this was not observed among women (sex-by-activity interaction, both p activity levels. Influence of activity was greater in older women: older women with low activity had lower Cort-vBMD than older men, but older women with high activity had higher Cort-vBMD than older men (age-by-sex-by-activity interaction, p=0.04). High heritability estimates for DXA and pQCT measures varied across bone sites. Percent time spent in moderate to vigorous activity had the most notable effect on bone, and in some cases, this effect was age or sex specific.

  16. Radiographic evaluation of bone adaptation adjacent to percutaneous osseointegrated prostheses in a sheep model.

    Science.gov (United States)

    Jeyapalina, Sujee; Beck, James Peter; Bachus, Kent N; Chalayon, Ornusa; Bloebaum, Roy D

    2014-10-01

    Percutaneous osseointegrated prostheses (POPs) are being investigated as an alternative to conventional socket suspension and require a radiographic followup in translational studies to confirm that design objectives are being met. In this 12-month animal study, we determined (1) radiographic signs of osseointegration and (2) radiographic signs of periprosthetic bone hypertrophy and resorption (adaptation) and (3) confirmed them with the histologic evidence of host bone osseointegration and adaptation around a novel, distally porous-coated titanium POP with a collar. A POP device was designed to fit the right metacarpal bone of sheep. Amputation and implantation surgeries (n = 14) were performed, and plane-film radiographs were collected quarterly for 12 months. Radiographs were assessed for osseointegration (fixation) and bone adaptation (resorption and hypertrophy). The cortical wall and medullary canal widths were used to compute the cortical index and expressed as a percentage. Based on the cortical index changes and histologic evaluations, bone adaptation was quantified. Radiographic data showed signs of osseointegration including those with incomplete seating against the collar attachment. Cortical index data indicated distal cortical wall thinning if the collar was not seated distally. When implants were bound proximally, bone resorbed distally and the diaphyseal cortex hypertrophied. Histopathologic evidence and cortical index measurements confirmed the radiographic indications of adaptation and osseointegration. Distal bone loading, through collar attachment and porous coating, limited the distal bone resorption. Serial radiographic studies, in either animal models or preclinical trials for new POP devices, will help to determine which designs are likely to be safe over time and avoid implant failures.

  17. The effect of radiation-sterilization conditions and preservation procedures on physico-chemical and biological properties of bone allografts

    International Nuclear Information System (INIS)

    Goclawska, A.D.; Kaminski, A.; Wasilewska, M.

    1999-01-01

    Radiation-sterilization of connective tissue allografts (bone including) with a dose of 35 kGy is routinely used in the Central Tissue Bank in Warsaw since 1963. This method of sterilization offers many advantages: good penetration ability, relatively low temperature rise, and possibility of sterilization of grafts in closed beforehand vials, which protects against secondary contamination. It should be kept in mind, however that high doses of ionizing radiation (in the range of 20-35 kGy) used for sterilization evoke many chemical and physical changes which may influence biological properties of grafts. These changes have been studied using various methodological approaches. Using electron paramagnetic resonance (EPR) spectrometry it has been found that in radiation-sterilized bone two types of paramagnetic entities are generated: i/ coliagen radicals which are unstable and disappear completely in the presence of air oxygen, ii/ very stable at room temperature paramagnetic defects (centers) localized in the crystalline lattice of bone mineral. These stable paramagnetic defects have been treated as a new kind of markers and used for: a/ quantitative evaluation of remodeling process of radiation-sterilized bone allografts preserved by lyophilization or deep freezing; b/ estimation of the dose of ionizing radiation absorbed by living organism in the case of accidental exposure (skeleton serving as a dosimeter) and for control of radiation-sterilization process. The effect of radiation-sterilization and preservation procedures on bone allografts was studied using a model of heterotopically induced osteogenesis and measuring the solubility of bone collagen in vitro. It has been observed that lyophilized bone allografts irradiated at room temp. with doses of 35 and 50 kGy, respectively, were very quickly resorbed in vivo and did not induce osteogenesis, while lyophilized as well as deep-frozen matrices irradiated at -7OoC were slowly resorbed and induced de novo bone fon

  18. Genetic ablation of CD68 results in mice with increased bone and dysfunctional osteoclasts.

    Directory of Open Access Journals (Sweden)

    Jason W Ashley

    Full Text Available CD68 is a member of the lysosome associated membrane protein (LAMP family that is restricted in its expression to cells of the monocyte/macrophage lineage. This lineage restriction includes osteoclasts, and, while previous studies of CD68 in macrophages and dendritic cells have proposed roles in lipid metabolism, phagocytosis, and antigen presentation, the expression and function of CD68 in osteoclasts have not been explored. In this study, we investigated the expression and localization of CD68 in macrophages and osteoclasts in response to the monocyte/macrophage-colony stimulating factor (M-CSF and the receptor activator of NF-κB ligand (RANKL. We found that M-CSF stimulates CD68 expression and RANKL alters the apparent molecular weight of CD68 as measured by Western immunoblotting. In addition, we explored the significance of CD68 expression in osteoclasts by generating mice that lack expression of CD68. These mice have increased trabecular bone, and in vitro assessment of CD68(-/- osteoclasts revealed that, in the absence of CD68, osteoclasts demonstrate an accumulation of intracellular vesicle-like structures, and do not efficiently resorb bone. These findings demonstrate a role for CD68 in the function of osteoclasts, and future studies will determine the mechanistic nature of the defects seen in CD68(-/- osteoclasts.

  19. Instrumental neutron activation analysis of prehistoric and ancient bone remains

    International Nuclear Information System (INIS)

    Vasidov, A.; Osinskaya, N.S.; Khatamov, Sh.; Rakhmanova, T.

    2008-01-01

    Instrumental neutron activation analysis (INAA) was used to study the element contents in bones of prehistoric dinosaurs and bones of an ancient bear and an archantrop (ancient person), which were found on the territory of Uzbekistan. Concentrations of more than 25 elements were in the range of 0.043-3600 mg/kg. Multielement analyses of bone and soil samples were carried out by INAA using the WWR-SM research nuclear reactor. Results of measurements have shown that in the dinosaurs bones the concentration of the rare earth elements (REEs) were within 280-3200 mg/kg; the uranium content reached a very high value, up to 180 mg/kg, while in soils coating the dinosaurs bones this content was 4.2 mg/kg; in the bones of the archantrop it was 1.53 mg/kg and in the bones of a standard person its amount is less than 0.016 mg/kg. (author)

  20. Cell fusion in osteoclasts plays a critical role in controlling bone mass and osteoblastic activity

    International Nuclear Information System (INIS)

    Iwasaki, Ryotaro; Ninomiya, Ken; Miyamoto, Kana; Suzuki, Toru; Sato, Yuiko

    2008-01-01

    The balance between osteoclast and osteoblast activity is central for maintaining the integrity of bone homeostasis. Here we show that mice lacking dendritic cell specific transmembrane protein (DC-STAMP), an essential molecule for osteoclast cell-cell fusion, exhibited impaired bone resorption and upregulation of bone formation by osteoblasts, which do not express DC-STAMP, which led to increased bone mass. On the contrary, DC-STAMP over-expressing transgenic (DC-STAMP-Tg) mice under the control of an actin promoter showed significantly accelerated cell-cell fusion of osteoclasts and bone resorption, with decreased osteoblastic activity and bone mass. Bone resorption and formation are known to be regulated in a coupled manner, whereas DC-STAMP regulates bone homeostasis in an un-coupled manner. Thus our results indicate that inhibition of a single molecule provides both decreased osteoclast activity and increased bone formation by osteoblasts, thereby increasing bone mass in an un-coupled and a tissue specific manner.

  1. Increased physical activity ameliorates high fat diet-induced bone resorption in mice

    Science.gov (United States)

    It has been recognized that mechanical stresses associated with physical activity (PA) have beneficial effects on increasing bone mineral density (BMD) and improving bone quality. On the other hand, high fat diet (HFD) and obesity increase bone marrow adiposity leading to increased excretion of pro-...

  2. Guided bone regeneration with a synthetic biodegradable membrane: a comparative study in dogs.

    Science.gov (United States)

    Jung, Ronald E; Kokovic, Vladimir; Jurisic, Milan; Yaman, Duygu; Subramani, Karthikeyan; Weber, Franz E

    2011-08-01

    The aim of the present study was to compare a newly developed biodegradable polylactide/polyglycolide/N-methyl-2-pyrrolidone (PLGA/NMP) membrane with a standard resorbable collagen membrane (RCM) in combination with and without the use of a bone substitute material (deproteinized bovine bone mineral [DBBM]) looking at the proposed tenting effect and bone regeneration. In five adult German sheepdogs, the mandibular premolars P2, P3, P4, and the molar M1 were bilaterally extracted creating two bony defects on each site. A total of 20 dental implants were inserted and allocated to four different treatment modalities within each dog: PLGA/NMP membrane only (Test 1), PLGA/NMP membrane with DBBM (Test 2), RCM only (negative control), and RCM with DBBM (positive control). A histomorphometric analysis was performed 12 weeks after implantation. For statistical analysis, a Friedman test and subsequently a Wilcoxon signed ranks test were applied. In four out of five PLGA/NMP membrane-treated defects, the membranes had broken into pieces without the support of DBBM. This led to a worse outcome than in the RCM group. In combination with DBBM, both membranes revealed similar amounts of area of bone regeneration and bone-to-implant contact without significant differences. On the level of the third implant thread, the PLGA/NMP membrane induced more horizontal bone formation beyond the graft than the RCM. The newly developed PLGA/NMP membrane performs equally well as the RCM when applied in combination with DBBM. Without bone substitute material, the PLGA/NMP membrane performed worse than the RCM in challenging defects, and therefore, a combination with a bone substitute material is recommended. © 2010 John Wiley & Sons A/S.

  3. Effect of vibration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

    Science.gov (United States)

    Suzuki, N.; Kitamura, K.; Nemoto, T.; Shimizu, N.; Wada, S.; Kondo, T.; Tabata, M. J.; Sodeyama, F.; Ijiri, K.; Hattori, A.

    In osteoclastic activity during space flight as well as hind limb unloading by tail suspension, inconsistent results have been reported in an in vivo study. The bone matrix plays an important role in the response to physical stress. However, there is no suitable in vitro co-culture system of osteoblasts and osteoclasts including bone matrix. On the other hand, fish scale is a calcified tissue that contains osteoblasts, osteoclasts, and bone matrix, all of which are similar to those found in human bones. Recently, we developed a new in vitro model system using goldfish scale. This system can detect the activities of osteoclasts and osteoblasts with tartrate-resistant acid phosphatase and alkaline phosphatase as the respective markers and precisely analyze the co-relationship between osteoblasts and osteoclasts. Using this system, we analyzed the bone metabolism under various degrees of acceleration (0.5-, 1-, 2-, 4-, and 6-G) by vibration with a G-load apparatus. After loading for 5 and 10 min, the scales were incubated for 6 and 24 h. The osteoblastic and osteoclastic activities were then measured. The osteoblastic activities gradually increased corresponding to 1-G to 6-G acceleration. In addition, ER mRNA expression was the highest under 6-G acceleration. On the other hand, the osteoclastic activity decreased at 24 h of incubation under low acceleration (0.5- and 1-G). This change coincided with TRAP mRNA expression. Under 2-G acceleration, the strength of suppression in osteoclastic activity was the highest. The strength of the inhibitory action under 4- and 6-G acceleration was lower than that under 2-G acceleration. In our co-culture system, osteoblasts and osteoclasts in the scale sensitively responded to several degrees of acceleration. Therefore, we strongly believe that our in vitro co-culture system is useful for the analysis of bone metabolism under loading or unloading.

  4. Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease.

    Science.gov (United States)

    Langlois, M R; Delanghe, J R; Kaufman, J M; De Buyzere, M L; Van Hoecke, M J; Leroux-Roels, G G

    1994-09-01

    Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase activity was measured after lectin precipitation using the Iso-ALP test kit. Mass concentration of bone alkaline phosphatase was determined with an immunoradiometric assay (Tandem-R Ostase). In general, serum bone alkaline phosphatase mass and activity concentration correlated well. The activity : mass ratio of bone alkaline phosphatase was low in hyperthyroidism. Activation energy of the reaction catalysed by bone alkaline phosphatase was high in osteoporosis and in hyperthyroidism. Experiments with neuraminidase digestion further demonstrated that the thermodynamic heterogeneity of bone alkaline phosphatase can be explained by a different glycosylation of the enzyme.

  5. Investigation of environmental activity levels of bone-coal mining area in five provinces

    International Nuclear Information System (INIS)

    Ye Jida; Wu Zongmei; Kong Lingli; Shi Jinhua; Li Ying; Jiang Shan; Zhang Liang

    2005-01-01

    During 1991-1993, the activity levels of the bone-coal mines were investigated in Zhejiang, Hubei, Hunan, Jiangxi and Anhui Province, respectively, where the reserve of bone-coal is about 90% of our country's total reserve. The average of γ radiation dose rate level measured for bone-coal, bone-coal cinder (BCC) and bone-coal cinder brick (BCCB) in these provinces is about 500 nGy/h, 400 nGy/h and 700 nGy/h respectively, while that for fields, roads and houses made of BCCB in corresponding regions of these provinces is about 200 nGy/h, 260 nGy/h and 300 nGy/h respectively. It is shown that the environmental activity level of bone-coal mining area is about 3 times higher than the reference spots. (authors)

  6. Annulus Fibrosus Can Strip Hyaline Cartilage End Plate from Subchondral Bone: A Study of the Intervertebral Disk in Tension.

    Science.gov (United States)

    Balkovec, Christian; Adams, Michael A; Dolan, Patricia; McGill, Stuart M

    2015-10-01

    Study Design Biomechanical study on cadaveric spines. Objective Spinal bending causes the annulus to pull vertically (axially) on the end plate, but failure mechanisms in response to this type of loading are poorly understood. Therefore, the objective of this study was to identify the weak point of the intervertebral disk in tension. Methods Cadaveric motion segments (aged 79 to 88 years) were dissected to create midsagittal blocks of tissue, with ∼10 mm of bone superior and inferior to the disk. From these blocks, 14 bone-disk-bone slices (average 4.8 mm thick) were cut in the frontal plane. Each slice was gripped by its bony ends and stretched to failure at 1 mm/s. Mode of failure was recorded using a digital camera. Results Of the 14 slices, 10 failed by the hyaline cartilage being peeled off the subchondral bone, with the failure starting opposite the lateral annulus and proceeding medially. Two slices failed by rupturing of the trabecular bone, and a further two failed in the annulus. Conclusions The hyaline cartilage-bone junction is the disk's weak link in tension. These findings provide a plausible mechanism for the appearance of bone and cartilage fragments in herniated material. Stripping cartilage from the bony end plate would result in the herniated mass containing relatively stiff cartilage that does not easily resorb.

  7. First forensic records of termite activity on non-fossilized human bones in Brazil

    Directory of Open Access Journals (Sweden)

    R. A. Queiroz

    Full Text Available Abstract The aim of this study was to describe the first records of termite activity on non-fossilized human bones in Brazil. The cases reported in this study resulted from forensic analysis of six human skeletons found in northeastern Brazil between 2012 and 2014. Traces of tunnels and nests commonly produced by termites were found on several human bone surfaces as well as the specimens and characteristic signs of osteophagic activity. In four cases, the species were identified: Amitermes amifer Silvestri, 1901, Nasutitermes corniger (Motschulsky, 1855 (on two skeletons, and Microcerotermes indistinctus Mathews, 1977. In two other cases, the activity of termites on bone surfaces was evidenced by remains of nests and tunnels produced by these insects. At least in the samples of human remains available for this report, the number of termites collected was greater on bones found during autumn, the rainy season in the Northeast of Brazil. The human bones examined showed termites like insects with lots of strength at bone degradation, capable of continuing the process of decomposition of human remains even in completely skeletonized bodies.

  8. Posterior lumbar interbody fusion using non resorbable poly-ether-ether-ketone versus resorbable poly-L-lactide-co-D,L-lactide fusion devices. Clinical outcome at a minimum of 2-year follow-up.

    Science.gov (United States)

    Jiya, Timothy U; Smit, T; van Royen, B J; Mullender, M

    2011-04-01

    Previous papers on resorbable poly-L-lactide-co-D,L-lactide (PLDLLA) cages in spinal fusion have failed to report adequately on patient-centred clinical outcome measures. Also comparison of PLDLLA cage with a traditionally applicable counterpart has not been previously reported. This is the first randomized prospective study that assesses clinical outcome of PLDLLA cage compared with a poly-ether-ether-ketone (PEEK) implant. Twenty-six patients were randomly assigned to undergo instrumented posterior lumbar interbody fusion (PLIF) whereby either a PEEK cage or a PLDLLA cage was implanted. Clinical outcome based on visual analogue scale scores for leg pain and back pain, as well as Oswestry Disability Index (ODI) and SF-36 questionnaires were documented and analysed. When compared with preoperative values, all clinical parameters have significantly improved in the PEEK group at 2 years after surgery with the exception of SF-36 general health, SF-36 mental health and SF-36 role emotional scores. No clinical parameter showed significant improvement at 2 years after surgery compared with preoperative values in the PLDLLA patient group. Only six patients (50%) in the PLDLLA group showed improvement in the VAS scores for leg and back pain as well as the ODI, as opposed to 10 patients (71%) in the PEEK group. One-third of the patients in the PLDLLA group actually reported worsening of their pain scores and ODI. Three cases of mild to moderate osteolysis were seen in the PLDLLA group. Following up on our preliminary report, these 2-year results confirm the superiority of the PEEK implant to the resorbable PLDLLA implant in aiding spinal fusion and alleviating symptoms following PLIF in patients with degenerative spondylolisthesis associated with either canal stenosis or foramen stenosis or both and emanating from a single lumbar segment.

  9. Holding fast.

    Science.gov (United States)

    Gourville, John T

    2005-06-01

    CEO Peter Walsh faces a classic innovator's dilemma. His company, Crescordia, produces high-quality metal plates, pins, and screws that orthopedic surgeons use to repair broken bones. In fact, because the company has for decades refused to compromise on quality, there are orthopedic surgeons who use nothing but Crescordia hardware. And now these customers have begun to clamor for the next generation technology: resorbable hardware. Resorbables offer clear advantages over the traditional hardware. Like dissolving sutures, resorbable plates and screws are made of biodegradable polymers. They hold up long enough to support a healing bone, then gradually and harmlessly disintegrate in the patient's body. Surgeons are especially looking forward to using resorbables on children, so kids won't have to undergo a second operation to remove the old hardware after their bones heal, a common procedure in pediatrics. The new products, however, are not yet reliable; they fail about 8% of the time, sometimes disintegrating before the bone completely heals and sometimes not ever fully disintegrating. That's why Crescordia, mindful of its hard-earned reputation, has delayed launching a line using the new technology. But time is running out. A few competitors have begun to sell resorbables despite their imperfections, and these companies are picking up market share. Should Crescordia join the fray and risk tarnishing its brand? Or should the company sit tight until it can offer a perfect product? Commenting on this fictional case study are Robert A. Lutz, vice chairman of product development at General Motors; Clayton M. Christensen, the Robert and Jane Cizik Professor of Business Administration at Harvard Business School; Jason Wittes, a senior equity analyst covering medical supplies and devices at Leerink Swann; and Nick Galakatos, a general partner of MPM Capital.

  10. Mesenchymal stem cells (MSCs) as skeletal therapeutics-an update

    DEFF Research Database (Denmark)

    Saeed, H.; Ahsan, M.; Saleem, Z.

    2016-01-01

    Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair....../regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range...

  11. Bone metabolic activity measured with positron emission tomography and [18F] fluoride ion in renal osteodystrophy: Correlation with bone histomorphometry

    International Nuclear Information System (INIS)

    Messa, C.; Goodman, W.G.; Hoh, C.K.; Choi, Y.; Nissenson, A.R.; Salusky, I.B.; Phelps, M.E.; Hawkins, R.A.

    1993-01-01

    The authors evaluated the bone metabolic activity in patients with renal osteodystrophy using positron emission tomography and [ 18 F] fluoride ion. Eight patients had secondary hyperparathyroidism (HPT), and three had low-turnover bone disease. Eleven normal subjects were also studied, and three of the eight HPT patients were reevaluated after therapy. A rate constant (K) describing the net transport of [ 18 F] fluoride ion into a bound compartment in bone was calculated using both a three-compartment model and Patlak graphical analysis. Values of K were compared with biochemical data and with histomorphometric indices. The results indicate that K is significantly higher (P 18 F] fluoride ion can differentiate low turnover from high turnover lesions of renal osteodystropy and provide quantitative estimates of bone cell activity that correlate with histomorphometric data

  12. System for estimation of mean active bone marrow dose

    International Nuclear Information System (INIS)

    Ellis, R.E.; Healy, M.J.R.; Shleien, B.; Tucker, T.

    1975-09-01

    The exposure measurements, model and computer program for estimation of mean active bone marrow doses formerly employed in the 1962 British Survey of x-ray doses and proposed for application to x-ray exposure information obtained in the U.S. Public Health Service's X-Ray Exposure Studies (1966 and 1973) are described and evaluated. The method described is feasible for use to determine the mean active bone marrow doses to adults for examinations having a skin to source distance of 80 cm or less. For a greater SSD, as for example in chest x rays, a small correction in the calculation dose can be made

  13. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    Science.gov (United States)

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  14. Constitutive activation of Gli2 impairs bone formation in postnatal growing mice.

    Directory of Open Access Journals (Sweden)

    Kyu Sang Joeng

    Full Text Available Indian hedgehog (Ihh signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation of Hedgehog (Hh signaling may enhance bone formation, we generated mice that expressed a constitutively active form of Gli2 in the Osx-lineage cells. Unexpectedly, these mice exhibited severe osteopenia due to a marked decrease in osteoblast number and function, although bone resorption was not affected. Quantitative analyses of the molecular markers indicated that osteoblast differentiation was impaired in the mutant mouse. However, the osteoblast-lineage cells isolated from these mice exhibited more robust osteoblast differentiation than normal in vitro. Similarly, pharmacological stimulation of Hh signaling enhanced osteoblast differentiation from Osx-expressing cells isolated from the wild-type mouse. Thus, even though Hh signaling directly promotes osteoblast differentiation in vitro, constitutive activation of this pathway impairs bone formation in vivo, perhaps through an indirect mechanism.

  15. Resorbable and running suture for stable fixation of amniotic membrane multilayers: A useful modification in deep or perforating sterile corneal ulcers

    Directory of Open Access Journals (Sweden)

    Constantin E. Uhlig

    2018-06-01

    Full Text Available Purpose: To present a modified technique for secure tightening and fixing of multilayer amniotic membranes in deep or perforating corneal ulcers. Observations: The modified procedure for application and fixation of multilayer amniotic membranes is retrospectively described step by step, and the results of three patients treated with this technique were retrospectively analysed and presented.The modification consists basically in fixing the inlays with one mini-overlay that is sutured intracorneally with resorbable and running Vicryl 10.0, before a corneoscleral overlay is fixed on top conjunctivally with a running nylon 10.0 suture. The resorbable Vicryl suture is left in place permanently. Conclusions and Importance: The method described avoids any risk of destroying or displacing the inlays by removing sutures later. In each of the three patients demonstrated as case reports the cornea remained stable throughout the 3- to 5-month follow-up period. This modified technique represents a very useful auxiliary means of treating deep or perforating non-infectious corneal ulcers. Keywords: Amniotic membrane transplantation, Corneal ulcer, Corneal perforation, Multilayer, Keratoplasty

  16. Preparation of Emulsifying Wax/GMO Nanoparticles and Evaluation as a Delivery System for Repurposing Simvastatin in Bone Regeneration.

    Science.gov (United States)

    Eskinazi-Budge, Aaron; Manickavasagam, Dharani; Czech, Tori; Novak, Kimberly; Kunzler, James; Oyewumi, Moses O

    2018-05-30

    Simvastatin (Sim) is a widely known drug in the treatment of hyperlipidemia that has attracted so much attention in bone regeneration based on its potential osteoanabolic effect. However, repurposing of Sim in bone regeneration will require suitable delivery systems that can negate undesirable off-target/side effects. In this study, we have investigated a new lipid nanoparticle (NP) platform that was fabricated using a binary blend of emulsifying wax (Ewax) and glyceryl monooleate (GMO). Using the binary matrix materials, NPs loaded with Sim (0-500 µg/mL) were prepared and showed an average particle size of about 150 nm. NP size stability was dependent on Sim concentration loaded in NPs. The suitability of NPs prepared with the binary matrix materials in Sim delivery for potential application in bone regeneration was supported by biocompatibility in pre-osteoclastic and pre-osteoblastic cells. Additional data demonstrated that biofunctional Sim was released from NPs that facilitated differentiation of osteoblasts (cells that form bones) while inhibiting differentiation of osteoclasts (cells that resorb bones). The overall work demonstrated the preparation of NPs from Ewax/GMO blends and characterization to ascertain potential suitability in Sim delivery for bone regeneration. Additional studies on osteoblast and osteoclast functions are warranted to fully evaluate the efficacy simvastatin-loaded Ewax/GMO NPs using in-vitro and in-vivo approaches.

  17. Role of notch signaling in osteoimmunology-from the standpoint of osteoclast differentiation

    NARCIS (Netherlands)

    Duan, Li; Ren, Yijin

    The Notch signaling pathway is a highly conserved cell signaling system present in most multicellular organisms. Osteoimmunology comprises the interplay between the immune system and bone metabolism. Osteoclasts, cells that resorb bone, play a crucial role in bone metabolism. In this review, we

  18. The calculation of annual limits of intake for plutonium-239 in man using a bone model which allows for plutonium burial and recycling

    International Nuclear Information System (INIS)

    Priest, N.D.; Hunt, B.W.

    1979-01-01

    Values of the annual limit intake (ALI) for plutonium-239 in man have been calculated using committed dose equivalent limits as recommended by ICRP in Publication 26. The calculations were made using a multicompartment bone model which allows for plutonium burial and recycling in the skeleton. In one skeletal compartment, the growing surfaces of cortical bone, it is assumed that plutonium deposits are retained and are not subject to resorption or recycling. In the trabecular bone compartment plutonium is taken to be resorbed with either subsequent redeposition onto bone surfaces or retention in the bone marrow. ALIs for plutonium-239 have been calculated assuming a range of rates of bone accretion (0 to 32 μm yr -1 ), different amounts of plutonium retained in the marrow (0 to 60%) and a 20%, 45% or 70% deposition of plutonium in the skeleton from the blood. The calculations made using this bone model suggest that 750 Bq (20 nCi) is an appropriate ALI for the inhalation of class W and class Y plutonium compounds and that 830 kBq and 5 MBq (23 μCi and 136 μCi) are the appropriate ALIs for the ingestion of soluble and insoluble forms of plutonium respectively. (author)

  19. The calculation of annual limits of intake for plutonium-239 in man using a bone model which allows for plutonium burial and recycling.

    Science.gov (United States)

    Priest, N D; Hunt, B W

    1979-05-01

    Values of the annual limit of intake (ALI) for plutonium-239 in man have been calculated using committed dose equivalent limits as recommended by ICRP in Publication 26. The calculations were made using a multicompartment bone model which allows for plutonium burial and recycling in the skeleton. In one skeletal compartment, the growing surfaces of cortical bone, it is assumed that plutonium deposits are retained and are not subject to resorption or recycling. In the trabecular bone compartment plutonium is taken to be resorbed with either subsequent redeposition onto bone surfaces or retention in the bone marrow. ALIs for plutonium-239 have been calculated assuming a range of rates of bone accretion (0-32 micron yr-1), different amounts of plutonium retained in the marrow (0-60%) and a 20%, 45% or 70% deposition of plutonium in the skeleton from the blood. The calculations made using this bone model suggest that 750 Bq (20 nCi) is an appropriate ALI for the inhalation of class W and class Y plutonium compounds and that 830 kBq and 5 MBq (23 muCi and 136 muCi) are the appropriate ALIs for the ingestion of soluble and insoluble forms of plutonium respectively.

  20. Long-term leisure time physical activity and properties of bone: a twin study.

    Science.gov (United States)

    Ma, Hongqiang; Leskinen, Tuija; Alen, Markku; Cheng, Sulin; Sipilä, Sarianna; Heinonen, Ari; Kaprio, Jaakko; Suominen, Harri; Kujala, Urho M

    2009-08-01

    Effects of physical activity on bone properties, when controlled for genetic effects, are not fully understood. We aimed to study the association between long-term leisure time physical activity (LTPA) and bone properties using twin pairs known to be discordant for leisure time physical activity for at least 30 yr. Volumetric BMD and geometric properties were measured at the tibia shaft and distal end using pQCT in 16 middle-aged (50-74 yr) same-sex twin pairs (seven monozygotic [MZ] and nine dizygotic [DZ] pairs) selected from a population-based cohort. Paired differences between active and inactive co-twins were studied. Active members of MZ twin pairs had larger cortical bone cross-sectional area (intrapair difference: 8%, p = 0.006), thicker cortex (12%, p = 0.003), and greater moment of inertia (I(max), 20%, p = 0.024) at the tibia shaft than their inactive co-twins. At the distal tibia, trabecular BMD (12%, p = 0.050) and compressive strength index (18%, p = 0.038) were also higher in physically active MZ pair members than their inactive co-twins. The trends were similar, but less consistently so, in DZ pairs as in MZ pairs. Our genetically controlled study design shows that LTPA during adulthood strengthens bones in a site-specific manner, that is, the long bone shaft has a thicker cortex, and thus higher bending strength, whereas the distal bone has higher trabecular density and compressive strength. These results suggest that LTPA has a potential causal role in decreasing the long-term risk of osteoporosis and thus preventing osteoporotic fractures.

  1. Neutron activation analysis of the prehistoric and ancient bone remains

    International Nuclear Information System (INIS)

    Vasidov, A.; Osinskaya, N.S.; Khatamov, Sh.; Rakhmanova, T.; Akhmadshaev, A.Sh.

    2006-01-01

    Full text: In the work results of the instrumental neutron activation analysis (INAA) of prehistoric bone remains of dinosaurs and ancient bones of bear, archantrop found out on the territory of Uzbekistan are presents. A bone of dinosaur from Mongolia, standard a bone of the person and soils taken from a surface and from of the femoral joint of a dinosaur were also subject to INAA. The INAA method determines of contents of about 30 elements in bones and soils in an interval 0.043-3600 mg / kg. Among found elements Ca (46 %), Sc, Cr, Fe (up to 2.2 g/kg), Ni, Zn, Sr (up to 3.6 g/kg), Sb, Ba, Sb and some others are mainly found in bones. The contents of some elements in bones of dinosaurs reach very high values 280-3200 mg / kg, and are mainly lanthanides La, Ce, Nd, Sm, Eu, Tb, Yb and Lu. In our opinion, lanthanides and some other elements, like As, Br, and Mo in bones were formed as a result of fission of uranium and transuranium elements. Because content of uranium in bones of dinosaurs is very high, up to 180 mg / kg, and those of thorium is 20 mg/ kg. However U and Th in soils are 4.8 mg/kg and 3.7 mg / kg, respectively. The content of uranium in bones of the archantrop is 1.53 mg / kg, while U in standard bone of the human is less than 0,016 mg/kg. (author)

  2. Microarray Profile of Gene Expression during Osteoclast Differentiation in Modeled Microgravity

    Data.gov (United States)

    National Aeronautics and Space Administration — Microgravity leads to a 10-15% loss of bone mass in astronauts during space flight. Osteoclast is the multinucleated bone resorbing cell. In this study we used NASA...

  3. Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty.

    Science.gov (United States)

    Tian, Xiao-bin; Sun, Li; Yang, Shu-hua; Zhang, Yu-kun; Hu, Ru-yin; Fu, De-hao

    2008-04-20

    Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 (hBMP2) gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects. Twenty four Kunming mice were randomly divided into two groups. The nanobone putty + hBMP2 plasmid was injected into the right thigh muscle pouches of the mice (experiment side). The nanobone putty + blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 (control side 1) or group 2 (control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty + hBMP2 plasmid; Group B, putty + blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone

  4. In vitro activation of bone with 14 MeV neutrons

    International Nuclear Information System (INIS)

    Holmberg, P.; Hyvoenen, M.; Tarvainen, M.

    1978-01-01

    Samples of compact bone, bone marrow and spongiosa of cow femur have been irradiated in vitro with 14 MeV neutrons. The Ca/P ratio for compact bone was found to be 2.16+-0.24. The suitability of using 14 MeV neutrons and the 31 P(n, α) 28 Al reaction for studying the bone mineral composition in vitro is discussed. It was demonstrated that 14 MeV neutrons can be used for the determination of calcium and phosphorus in bone with the aid of the 44 Ca(n, p) 44 K and 31 P(n, α) 28 Al reactions, respectively. As the Ca/P ratio for compact bone is known, the calcium content can be deduced indirectly from a determination of the phosphorus. This method has the advantage of not requiring moderator materials, as in the case when the 48 Ca(n, γ) 49 Ca reaction is employed. The half-life of the 28 Al activity is short (T=2.243 m) so that only short irradiation times are necessary. (T.G.)

  5. Rehabilitation of resorbed mandibular ridges using mini implant retained overdentures: A case series with 3 year follow-up

    Directory of Open Access Journals (Sweden)

    Pooja Kumari

    2016-01-01

    Full Text Available With the increasing average life expectancy of human beings, the need to cater geriatric patients is ever increasing. Complete dentures are an indispensable tool in this regard. The loose and unstable lower complete denture owing to residual ridge resorption is one of the most common problems faced by edentulous patients. Dental implant retained overdentures have emerged as an efficient treatment modality for such patients. Though useful, not every patient is a suitable candidate to go for conventional implant-borne prosthesis, limitation being the available bone width. In such cases, mini implants may be used for augmenting the retention of the dentures and improving the quality of life of patients. In this case series, rehabilitation of three compromised cases with mini implant retained overdentures have been described wherein patients are experiencing instability of lower denture due to thin resorbed mandibular ridges. In one of the cases, three mini implants placed in A, C, and E position were splinted using a cemented bar to retain the mandibular denture. The other two cases were rehabilitated using unsplinted ball type one piece mini implants placed in A, C, and E position in one case and B and D position in another case. Though splinted bar design should be preferred but the lack of available vertical space precluded the utilization of bar in other two cases. The results were found to be satisfactory with no complications reported during a follow-up period of over 3 years in all the cases.

  6. Sinus Floor Elevation and Augmentation Using Synthetic Nanocrystalline and Nanoporous Hydroxyapatite Bone Substitute Materials: Preliminary Histologic Results.

    Science.gov (United States)

    Belouka, Sofia-Maria; Strietzel, Frank Peter

    To compare the tissue composition of augmented sites after using two different synthetic bone substitute materials, nanocrystalline and nanoporous hydroxyapatite (HA), for sinus floor elevation and augmentation. Forty-four patients received 88 titanium screw implants (Camlog Promote plus) of 4.3-mm diameter and 11- or 13-mm length, placed simultaneously during sinus floor elevation and augmentation. Nanocrystalline (Ostim) or nanoporous (NanoBone) HA were used exclusively. Bone substitute materials and implant lengths were allocated by randomization. Bone biopsy specimens were obtained from the former area of the lateral access window at implant exposure during healing abutment placement after 6 months. Biopsy specimens were prepared and examined histologically and histomorphometrically. All implants were osseointegrated at the time of exposure. Clinically and histologically, no signs of inflammation in the augmented sites were present. The histomorphometric analysis of 44 biopsy specimens revealed 31.8% ± 11.6% newly formed bone for sites augmented with nanocrystalline HA and 34.6% ± 9.2% for nanoporous HA (P = .467). The proportion of remaining bone substitute material was 28.4% ± 18.6% and 30% ± 13%, respectively (P = .453). The proportion of soft tissue within the biopsy specimens was 39.9% ± 11.1% and 35.4% ± 6.8%, respectively (P = .064). No significant differences were found between the area fractions of bone, bone substitute material, and soft tissue concerning the bone substitute material utilized. Within the present study, both synthetic bone substitute materials, nanocrystalline and nanoporous HA, were found to support bone formation in sinus floor elevation and augmentation procedures by osteoconductivity. They were not completely resorbed after 6 months. The amounts of newly formed bone, soft tissue, and bone substitute material remnants were found to be similar, indicating that both materials are likewise suitable for sinus floor elevation and

  7. Evaluating adhesion reduction efficacy of type I/III collagen membrane and collagen-GAG resorbable matrix in primary flexor tendon repair in a chicken model.

    Science.gov (United States)

    Turner, John B; Corazzini, Rubina L; Butler, Timothy J; Garlick, David S; Rinker, Brian D

    2015-09-01

    Reduction of peritendinous adhesions after injury and repair has been the subject of extensive prior investigation. The application of a circumferential barrier at the repair site may limit the quantity of peritendinous adhesions while preserving the tendon's innate ability to heal. The authors compare the effectiveness of a type I/III collagen membrane and a collagen-glycosaminoglycan (GAG) resorbable matrix in reducing tendon adhesions in an experimental chicken model of a "zone II" tendon laceration and repair. In Leghorn chickens, flexor tendons were sharply divided using a scalpel and underwent repair in a standard fashion (54 total repairs). The sites were treated with a type I/III collagen membrane, collagen-GAG resorbable matrix, or saline in a randomized fashion. After 3 weeks, qualitative and semiquantitative histological analysis was performed to evaluate the "extent of peritendinous adhesions" and "nature of tendon healing." The data was evaluated with chi-square analysis and unpaired Student's t test. For both collagen materials, there was a statistically significant improvement in the degree of both extent of peritendinous adhesions and nature of tendon healing relative to the control group. There was no significant difference seen between the two materials. There was one tendon rupture observed in each treatment group. Surgical handling characteristics were subjectively favored for type I/III collagen membrane over the collagen-GAG resorbable matrix. The ideal method of reducing clinically significant tendon adhesions after injury remains elusive. Both materials in this study demonstrate promise in reducing tendon adhesions after flexor tendon repair without impeding tendon healing in this model.

  8. A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts

    DEFF Research Database (Denmark)

    Henriksen, Kim; Andreassen, Kim V; Thudium, Christian S

    2012-01-01

    Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium wa...... dependent and independent of their resorptive activity, secrete factors stimulating osteoblastic bone formation.......Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium...... release. The osteoblastic cell line 2T3 was treated with 50% of CM or non-CM for 12days. Bone formation was assessed by Alizarin Red extraction. CM from mature osteoclasts induced bone formation, while CM from macrophages did not. Non-resorbing osteoclasts generated from osteopetrosis patients showed...

  9. Physical activity and bone: The importance of the various mechanical stimuli for bone mineral density. A review

    Directory of Open Access Journals (Sweden)

    Bente Morseth

    2011-08-01

    Full Text Available Numerous studies have reported benefits of regular physical activity on bone mineral density (BMD. The effects of physical activity on BMD are primarily linked to the mechanisms of mechanical loading, but the understanding of the precise mechanism behind the association is incomplete. The aim of this paper was to review the main findings concerning sources and types of mechanical stimuli in relation to BMD. Mechanical forces that act on bone are generated from impact with the ground (ground-reaction forces and from skeletal muscle contractions (muscle forces or muscle-joint forces, but the relative importance of these two sources has not been elucidated. Both muscle-joint forces and gravitational forces seem to be able to induce bone adaptation independently, and there may be differences in the importance of loading sources at different skeletal sites. The nature of the stimuli is affected by the type, intensity, frequency, and duration of the activity. The activity should be dynamic, not static, and the magnitude and rate of the stimuli should be high. In accordance with this, cross-sectional studies report highest BMD in athletes of high-impact activities such as dancing, soccer, volleyball, basketball, squash, speed skating, gymnastics, hockey, and step-aerobics. Endurance activities such as orienteering, skiing, and triathlon seem to be beneficial to a lesser degree, whereas low-impact activities such as swimming and cycling are associated with lower BMD than controls. Both the intensity and frequency of the activity should be varied and increased beyond the habitual level. Duration of the activity seems to be less important, and a few loading cycles seem to be sufficient.

  10. Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep.

    Science.gov (United States)

    van der Pol, U; Mathieu, L; Zeiter, S; Bourban, P-E; Zambelli, P-Y; Pearce, S G; Bouré, L P; Pioletti, D P

    2010-09-01

    Previous studies support resorbable biocomposites made of poly(L-lactic acid) (PLA) and beta-tricalcium phosphate (TCP) produced by supercritical gas foaming as a suitable scaffold for tissue engineering. The present study was undertaken to demonstrate the biocompatibility and osteoconductive properties of such a scaffold in a large animal cancellous bone model. The biocomposite (PLA/TCP) was compared with a currently used beta-TCP bone substitute (ChronOS, Dr. Robert Mathys Foundation), representing a positive control, and empty defects, representing a negative control. Ten defects were created in sheep cancellous bone, three in the distal femur and two in the proximal tibia of each hind limb, with diameters of 5 mm and depths of 15 mm. New bone in-growth (osteoconductivity) and biocompatibility were evaluated using microcomputed tomography and histology at 2, 4 and 12 months after surgery. The in vivo study was validated by the positive control (good bone formation with ChronOS) and the negative control (no healing with the empty defect). A major finding of this study was incorporation of the biocomposite in bone after 12 months. Bone in-growth was observed in the biocomposite scaffold, including its central part. Despite initial fibrous tissue formation observed at 2 and 4 months, but not at 12 months, this initial fibrous tissue does not preclude long-term application of the biocomposite, as demonstrated by its osteointegration after 12 months, as well as the absence of chronic or long-term inflammation at this time point. 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  11. Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

    Directory of Open Access Journals (Sweden)

    Mao-yin Zhang

    2015-01-01

    Full Text Available Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI. Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg were administrated intragastrically at early phase of postoperation (before pain appearance and later phase of postoperation (after pain appearance, respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-α and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1β increase. Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase.

  12. Osteoclasts from patients with autosomal dominant osteopetrosis type I caused by a T253I mutation in low-density lipoprotein receptor-related protein 5 are normal in vitro, but have decreased resorption capacity in vivo

    DEFF Research Database (Denmark)

    Henriksen, Kim; Gram, Jeppe; Høegh-Andersen, Pernille

    2005-01-01

    of osteoclast markers, morphology, and localization of proteins involved in bone resorption, such as ClC-7 and cathepsin K. The ability to resorb bone was also normal. In vivo, we compared the bone resorption and bone formation response to T3 in ADOI patients and age- and sex-matched controls. We found...

  13. Bone metabolic activity in hyperostosis cranialis interna measured with 18F-fluoride PET

    International Nuclear Information System (INIS)

    Waterval, Jerome J.; Dongen, Thijs M.A. van; Stokroos, Robert J.; Manni, Johannes J.; Teule, Jaap G.J.; Kemerink, Gerrit J.; Brans, Boudewijn; Nieman, Fred H.M.

    2011-01-01

    18 F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves. The aim of this study is to compare standardised uptake values (SUVs) at different sites in order to quantify bone metabolism in the affected anatomical regions in HCI patients. Nine affected family members, seven non-affected family members and nine non-HCI non-family members underwent 18 F-fluoride PET/CT scans. SUVs were systematically measured in the different regions of interest: frontal bone, sphenoid bone, petrous bone and clivus. Moreover, the average 18 F-fluoride uptake in the entire skull was measured by assessing the uptake in axial slides. Visual assessment of the PET scans of affected individuals was performed to discover the process of disturbed bone metabolism in HCI. 18 F-Fluoride uptake is statistically significantly higher in the sphenoid bone and clivus regions of affected family members. Visual assessment of the scans of HCI patients is relevant in detecting disease severity and the pattern of disturbed bone metabolism throughout life. 18 F-Fluoride PET/CT is useful in quantifying the metabolic activity in HCI and provides information about the process of disturbed bone metabolism in this specific disorder. Limitations are a narrow window between normal and pathological activity and the influence of age. This study emphasises that 18 F-fluoride PET/CT may also be a promising diagnostic tool for other metabolic bone disorders, even those with an indolent course. (orig.)

  14. Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

    Science.gov (United States)

    Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2017-01-01

    Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

  15. Top 10 Research Questions Related to Physical Activity and Bone Health in Children and Adolescents

    Science.gov (United States)

    Janz, Kathleen F.; Thomas, David Q.; Ford, M. Allison; Williams, Skip M.

    2015-01-01

    Evidence strongly supports a positive, causal effect of physical activity on bone strength and suggests long-term benefits of childhood physical activity to the prevention of osteoporosis. The contribution of healthy bone development in youth is likely to be as important to fracture prevention as the amount of late adulthood bone loss. Families,…

  16. Polymer-ceramic nanocomposites for applications in the bone surgery

    Science.gov (United States)

    Stodolak, E.; Gadomska, K.; Lacz, A.; Bogun, M.

    2009-01-01

    The subject of this work was preparation and investigation of properties of a nanocomposite material based on polymer matrix modified with nanometric silica particles (SiO2). The composite matrix consisted of resorbable P(L/DL)LA polymer with certified biocompatibility. Nanometric silica was introduced into the matrix by means of ultrasonic homogenisation and/or mechanical stirring. The silica was introduced directly e.g. as nanoparticles or inside calcium alginate fibres which contained 3 wt.% of amorphous SiO2. Proper dispersion of nano-filliers was confirmed by means of thermal analysis (TG/DTA, DSC). It was observed, that the presence of inorganic nanoparticles influenced several surface parameters of the nanocomposites i.e. hydrophility (a decrease of surface energy) and topography (both in micro- and nano-scale). Additionally, the nanocomposites exhibited enhanced mechanical properties (Young's modulus, tensile strength) compared to the pure polymer. The nanocomposites were bioactive materials (SBF/3 days/37oC). Biological tests (MTT test) showed a good viability of human osteoblasts (hFOB 1.19) in contact with the nanocomposites surface. Results of preliminary biological tests carried out with the use of mother cells extracted from human bone marrow showed that the nanocomposites may provide differenation of bone cells.

  17. Polymer-ceramic nanocomposites for applications in the bone surgery

    International Nuclear Information System (INIS)

    Stodolak, E; Gadomska, K; Lacz, A; Bogun, M

    2009-01-01

    The subject of this work was preparation and investigation of properties of a nanocomposite material based on polymer matrix modified with nanometric silica particles (SiO 2 ). The composite matrix consisted of resorbable P(L/DL)LA polymer with certified biocompatibility. Nanometric silica was introduced into the matrix by means of ultrasonic homogenisation and/or mechanical stirring. The silica was introduced directly e.g. as nanoparticles or inside calcium alginate fibres which contained 3 wt.% of amorphous SiO 2 . Proper dispersion of nano-filliers was confirmed by means of thermal analysis (TG/DTA, DSC). It was observed, that the presence of inorganic nanoparticles influenced several surface parameters of the nanocomposites i.e. hydrophility (a decrease of surface energy) and topography (both in micro- and nano-scale). Additionally, the nanocomposites exhibited enhanced mechanical properties (Young's modulus, tensile strength) compared to the pure polymer. The nanocomposites were bioactive materials (SBF/3 days/37 deg. C). Biological tests (MTT test) showed a good viability of human osteoblasts (hFOB 1.19) in contact with the nanocomposites surface. Results of preliminary biological tests carried out with the use of mother cells extracted from human bone marrow showed that the nanocomposites may provide differenation of bone cells.

  18. Physical activity programs for promoting bone mineralization and growth in preterm infants.

    Science.gov (United States)

    Schulzke, Sven M; Kaempfen, Siree; Trachsel, Daniel; Patole, Sanjay K

    2014-04-22

    Lack of physical stimulation may contribute to metabolic bone disease of preterm infants, resulting in poor bone mineralization and growth. Physical activity programs combined with adequate nutrition might help to promote bone mineralization and growth. The primary objective was to assess whether physical activity programs in preterm infants improve bone mineralization and growth and reduce the risk of fracture.The secondary objectives included other potential benefits in terms of length of hospital stay, skeletal deformities and neurodevelopmental outcomes, and adverse events.Subgroup analysis:• Given that the smallest infants are most vulnerable for developing osteopenia (Bishop 1999), a subgroup analysis was planned for infants with birth weight affect an infant's ability to increase bone mineral content (Kuschel 2004). Therefore, an additional subgroup analysis was planned for infants receiving different amounts of calcium and phosphorus, along with full enteral feeds as follows. ∘ Below 100 mg/60 mg calcium/phosphorus or equal to/above 100 mg/60 mg calcium/phosphorus per 100 mL milk. ∘ Supplementation of calcium without phosphorus. ∘ Supplementation of phosphorus without calcium. The standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used. The search included the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 9), MEDLINE, EMBASE, CINAHL (1966 to March 2013), and cross-references, as well as handsearching of abstracts of the Society for Pediatric Research and the International Journal of Sports Medicine. Randomized and quasi-randomized controlled trials comparing physical activity programs (extension and flexion, range-of-motion exercises) versus no organized physical activity programs in preterm infants. Data collection, study selection, and data analysis were performed according to the methods of the CNRG. Eleven trials enrolling 324 preterm infants (gestational age 26 to 34 weeks) were included in this

  19. Pharmacological activation of aldehyde dehydrogenase 2 promotes osteoblast differentiation via bone morphogenetic protein-2 and induces bone anabolic effect

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, Monika; Pal, Subhashis; China, Shyamsundar Pal; Porwal, Konica [Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Lucknow 226031 (India); Dev, Kapil [Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Shrivastava, Richa [Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Raju, Kanumuri Siva Rama; Rashid, Mamunur [Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Trivedi, Arun Kumar; Sanyal, Sabyasachi [Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Wahajuddin, Muhammad [Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Bhaduria, Smrati [Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Maurya, Rakesh [Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Chattopadhyay, Naibedya, E-mail: n_chattopadhyay@cdri.res.in [Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Lucknow 226031 (India)

    2017-02-01

    Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2). Silencing ALDH2 in osteoblasts abolished the alda-1 effects. Further, alda-1 attenuated the acetaldehyde-induced lipid-peroxidation and oxidative stress. BMP-2 is essential for bone regeneration and alda-1 increased its expression in osteoblasts. We then showed that alda-1 (40 mg/kg dose) augmented bone regeneration at the fracture site with concomitant increase in BMP-2 protein compared with control. The osteogenic dose (40 mg/kg) of alda-1 attained a bone marrow concentration that was stimulatory for osteoblast differentiation, suggesting that the tissue concentration of alda-1 matched its pharmacologic effect. In addition, alda-1 promoted modeling-directed bone growth and peak bone mass achievement, and increased bone mass in adult rats which reiterated its osteogenic effect. In osteopenic ovariectomized (OVX) rats, alda-1 reversed trabecular osteopenia with attendant increase in serum osteogenic marker (procollagen type I N-terminal peptide) and decrease in oxidative stress. Alda-1 has no effect on liver and kidney function. We conclude that activating ALDH2 by alda-1 had an osteoanabolic effect involving increased osteoblastic BMP-2 production and decreased OVX-induced oxidative stress. - Highlights: • Alda-1 induced osteoblast differentiation that involved upregulation of ALDH2 and BMP-2 • Alda-1

  20. The Association of Endothelin-1 Signaling with Bone Alkaline Phosphatase Expression and Protumorigenic Activities in Canine Osteosarcoma.

    Science.gov (United States)

    Neumann, Z L; Pondenis, H C; Masyr, A; Byrum, M L; Wycislo, K L; Fan, T M

    2015-01-01

    Canine osteosarcoma (OS) is an aggressive sarcoma characterized by pathologic skeletal resorption and pulmonary metastases. A number of negative prognostic factors, including bone alkaline phosphatase, have been identified in dogs with OS, but the underlying biologic factors responsible for such observations have not been thoroughly investigated. Endothelin-1-mediated signaling is active during bone repair, and is responsible for osteoblast migration, survival, proliferation, and bone alkaline phosphatase expression. The endothelin-1 signaling axis is active in canine OS cells, and this pathway is utilized by malignant osteoblasts for promoting cellular migration, survival, proliferation, and bone alkaline phosphatase activities. 45 dogs with appendicular OS. The expressions of endothelin-1 and endothelin A receptor were studied in OS cell lines and in samples from spontaneously occurring tumors. Activities mediated by endothelin-1 signaling were investigated by characterizing responses in 3 OS cell lines. In 45 dogs with OS, bone alkaline phosphatase concentrations were correlated with primary tumor osteoproductivity. Canine OS cells express endothelin-1 and endothelin A receptor, and this signaling axis mediates OS migration, survival, proliferation, and bone alkaline phosphatase activities. In OS-bearing dogs, circulating bone alkaline phosphatase activities were positively correlated with primary tumor relative bone mineral densities. Canine OS cells express endothelin-1 and functional endothelin A receptors, with the potential for a protumorigenic signaling loop. Increases in bone alkaline phosphatase activity are associated with osteoblastic OS lesions, and might be an epiphenomenon of active endothelin-1 signaling or excessive osteoproduction within the localized bone microenvironment. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  1. Bone mineral response to ammonium sulphate offered as a lick supplement in beef calves

    Directory of Open Access Journals (Sweden)

    L.E. Motsei

    2006-06-01

    Full Text Available Sixteen Bonsmara calves (4 males, 12 females between 10 and 18 months of age were blocked according to age and sex and randomly assigned to 2 groups. They were offered licks containing bone meal and salt (50:50 ratio (control and bone meal and ammonium sulphate (NH4SO4 at 1.25, 2.5, 5, 10, 15, and 18 % (treatment to evaluate the effects of dietary anions on bone phosphate (P concentration. Bone P concentration was significantly (P<0.05 higher in the NH4SO4 group compared with the control group, indicating that NH4SO4 was able to increase the P content of bone at each of the 6 concentrations used in the lick relative to the control animals, thereby improving the P status of the animals. Ammonium sulphate at 15% and 18% in the lick also significantly (P <0.05 increased bone P compared with the lower concentrations of NH4SO4. Bone calcium (Ca fluctuated as a result of the acidogenic lick. There was absorption of Ca when P was being resorbed and resorption of Ca when P was being absorbed into and out of bone. Bone Ca:P ratio ranged from 3.2 to 6.4 among the control group and 1.6 to 4.3 among the treatment group. Animals receiving the acidogenic lick had a higher percentage ash compared to the control group for most of the experimental period. Bone magnesium (Mg fluctuated in response to the acidogenic lick, and it was difficult to show a relationship between bone Mg and Ca or P. The overall mean cortical bone thickness was significantly (P < 0.05 greater in treatment (1.60 mm compared with control (1.43 mm calves and this was also true at sampling periods 2, 4, 5 and 6. Bone thickness followed bone P and not bone Ca. Results from this research indicate that the addition of ammonium sulphate to a lick had a beneficial effect in improving the P status by increasing bone P and improving the mineral status of bone by increasing the thickness of cortical bone and percentage ash.

  2. Bone mineral density in subjects using central nervous system-active medications.

    Science.gov (United States)

    Kinjo, Mitsuyo; Setoguchi, Soko; Schneeweiss, Sebastian; Solomon, Daniel H

    2005-12-01

    Decreased bone mineral density defines osteoporosis according to the World Health Organization and is an important predictor of future fractures. The use of several types of central nervous system-active drugs, including benzodiazepines, anticonvulsants, antidepressants, and opioids, have all been associated with increased risk of fracture. However, it is unclear whether such an increase in risk is related to an effect of bone mineral density or to other factors, such as increased risk of falls. We sought to examine the relationship between bone mineral density and the use of benzodiazepines, anticonvulsants, antidepressants, and opioids in a representative US population-based sample. We analyzed data on adults aged 17 years and older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Total femoral bone mineral density of 7114 male and 7532 female participants was measured by dual-energy x-ray absorptiometry. Multivariable linear regression models were used to quantify the relation between central nervous system medication exposure and total femoral bone mineral density. Models controlled for relevant covariates, including age, sex, and body mass index. In linear regression models, significantly reduced bone mineral density was found in subjects taking anticonvulsants (0.92 g/cm2; 95% confidence interval [CI]: 0.89 to 0.94) and opioids (0.92 g/cm2; 95% CI: 0.88 to 0.95) compared with nonusers (0.95 g/cm2; 95% CI: 0.95 to 0.95) after adjusting for several potential confounders. The other central nervous system-active drugs--benzodiazepines or antidepressants--were not associated with significantly reduced bone mineral density. In cross-sectional analysis of NHANES III, anticonvulsants and opioids (but not benzodiazepines or antidepressants) were associated with significantly reduced bone mineral density. These findings have implications for fracture-prevention strategies.

  3. Objectively measured physical activity and bone strength in 9-year-old boys and girls.

    Science.gov (United States)

    Sardinha, Luís B; Baptista, Fátima; Ekelund, Ulf

    2008-09-01

    The purpose of this work was to analyze the relationship between intensity and duration of physical activity and composite indices of femoral neck strength and bone-mineral content of the femoral neck, lumbar spine, and total body. Physical activity was assessed by accelerometry in 143 girls and 150 boys (mean age: 9.7 years). Measurement of bone-mineral content, femoral neck bone-mineral density, femoral neck width, hip axis length, and total body fat-free mass was performed with dual-energy radiograph absorptiometry. Compressive [(bone-mineral density x femoral neck width/weight)] and bending strength [(bone-mineral density x femoral neck width(2))/(hip axis length x weight)] express the forces that the femoral neck has to withstand in weight bearing, whereas impact strength [(bone-mineral density x femoral neck width x hip axis length)/(height x weight)] expresses the energy that the femoral neck has to absorb in an impact from standing height. Analysis of covariance (fat-free mass and age adjusted) showed differences between boys and girls of approximately 9% for compressive, 10% for bending, and 9% for impact strength. Stepwise regression analysis using time spent at sedentary, light, moderate, and vigorous physical activity as predictors revealed that vigorous physical activity explained 5% to 9% of femoral neck strength variable variance in both genders, except for bending strength in boys, and approximately 1% to 3% of total body and femoral neck bone-mineral content variance. Vigorous physical activity was then used to categorize boys and girls into quartiles. Pairwise comparison indicated that boys in the third and fourth quartiles (accumulation of >26 minutes/day) demonstrated higher compressive (11%-12%), bending (10%), and impact (14%) strength than boys in the first quartile. In girls, comparison revealed a difference between the fourth (accumulation of >25 minutes/day) and first quartiles for bending strength (11%). We did not observe any

  4. Calcium-41 as a long-term biological tracer for bone resorption

    Science.gov (United States)

    Elmore, David; Bhattacharyya, Maryka H.; Sacco-Gibson, Nancy; Peterson, David P.

    1990-12-01

    The use of 41Ca (half-life 1 × 10 5 yr) as a tracer for studying calcium metabolism in living systems is compared to the shorter-lived radionuclides 45Ca (165 d) and 47Ca (45 d) and the stable isotopes 42Ca and 44Ca. The feasibility of using accelerator mass spectrometry (AMS) measurements of 41Ca for studying multi-year calcium resorption in humans was tested as part of a companion study that used 45Ca to measure the effects of dietary cadmium on calcium metabolism in dogs. It was shown that Ca resorbed from prelabeled bones correlates well with 45Ca for a period of 28 weeks. The advantage of 41Ca is that, even with a negligible radiation dose, it can be measured by AMS long after the 45Ca becomes unmeasurable.

  5. Data Mining Activities for Bone Discipline - Current Status

    Science.gov (United States)

    Sibonga, J. D.; Pietrzyk, R. A.; Johnston, S. L.; Arnaud, S. B.

    2008-01-01

    The disciplinary goals of the Human Research Program are broadly discussed. There is a critical need to identify gaps in the evidence that would substantiate a skeletal health risk during and after spaceflight missions. As a result, data mining activities will be engaged to gather reviews of medical data and flight analog data and to propose additional measures and specific analyses. Several studies are briefly reviewed which have topics that partially address these gaps in knowledge, including bone strength recovery with recovery of bone mass density, current renal stone formation knowledge, herniated discs, and a review of bed rest studies conducted at Ames Human Research Facility.

  6. A morphometric study of bone surfaces and skin reactions after stimulation with static magnetic fields in rats

    Energy Technology Data Exchange (ETDEWEB)

    Linder-Aronson, S.; Lindskog, S. (Karolinska Institutet, Stockholm (Sweden))

    1991-01-01

    The present investigation was undertaken to measure any bone surface changes after stimulation with orthodontic magnets and, furthermore, to examine the soft tissue in immediate contact with the magnets. Both distal parts of the tibial hind legs in six groups of young rats were fitted with devices holding two orthodontic magnets in the experimental legs and similar devices without magnets in the control legs. The animals were killed after 2, 3, and 4 weeks. Morphometric evaluation showed significant increases in resorbing areas after 3 and 4 weeks. Similarly, a reduction was evident in the number of epithelial cells under the areas where the magnets had been applied. These findings indicate that the stimulation of bone resorption in the present study may have been caused by inhibition of the bone-lining osteoblasts. This proposition is supported by the apparent inhibitory effect of the magnetic fields on epithelial recycling that was seen as a reduced thickness of the epithelium under the magnets. Consequently, static magnetic fields should be used with care in orthodontic practice until a more complete understanding of their mechanism of action has been established.

  7. A morphometric study of bone surfaces and skin reactions after stimulation with static magnetic fields in rats.

    Science.gov (United States)

    Linder-Aronson, S; Lindskog, S

    1991-01-01

    The present investigation was undertaken to measure any bone surface changes after stimulation with orthodontic magnets and, furthermore, to examine the soft tissue in immediate contact with the magnets. Both distal parts of the tibial hind legs in six groups of young rats were fitted with devices holding two orthodontic magnets in the experimental legs and similar devices without magnets in the control legs. The animals were killed after 2, 3, and 4 weeks. Morphometric evaluation showed significant increases in resorbing areas after 3 and 4 weeks. Similarly, a reduction was evident in the number of epithelial cells under the areas where the magnets had been applied. These findings indicate that the stimulation of bone resorption in the present study may have been caused by inhibition of the bone-lining osteoblasts. This proposition is supported by the apparent inhibitory effect of the magnetic fields on epithelial recycling that was seen as a reduced thickness of the epithelium under the magnets. Consequently, static magnetic fields should be used with care in orthodontic practice until a more complete understanding of their mechanism of action has been established.

  8. The relation between bone demineralization, physical activity and anthropometric standards

    Directory of Open Access Journals (Sweden)

    Milena Barbosa Camara

    2017-03-01

    Full Text Available This paper aimed to verify the correlation between bone mineral density and the level of physical activity, as well as the food intake and the anthropometric parameters. It intended to analyse the bone mineral density (BMD of menopausal women through the bone densitometry test (DO in the lumbar region (L1 to L4, femoral neck and total femur, and also use Bouchard’s self-recall of daily activities; employing the food record from Buker and Stuart to dose and quantify the daily intake of calcium and vitamin D. The data were analysed via Kolmogorov-Smirnov’s test, and default value of α = 0.05 was set to compare the BMD averages. It was observed that one hundred percent of the assessed individuals had a BMD level below the average fixed by WHO: 14.4% with osteopenia and 85.6% with osteoporosis; a lower BMD in the femoral area (0.721g and the biggest loss among the sedentary ones (0.698g. It was noticed that there was a correlation between the physical activities and the BMD only when associated with anthropometric standards and the daily ingestion of vitamin D.

  9. Recombinant human bone morphogenetic protein induces bone formation

    International Nuclear Information System (INIS)

    Wang, E.A.; Rosen, V.; D'Alessandro, J.S.; Bauduy, M.; Cordes, P.; Harada, T.; Israel, D.I.; Hewick, R.M.; Kerns, K.M.; LaPan, P.; Luxenberg, D.P.; McQuaid, D.; Moutsatsos, I.K.; Nove, J.; Wozney, J.M.

    1990-01-01

    The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

  10. Effects of a perfusion bioreactor activated novel bone substitute in spine fusion in sheep

    DEFF Research Database (Denmark)

    Sørensen, Jesper Roed; Koroma, Kariatta Ester; Ding, Ming

    2012-01-01

    To evaluate the effect of a large perfusion-bioreactor cell-activated bone substitute, on a two-level large posterolateral spine fusion sheep model.......To evaluate the effect of a large perfusion-bioreactor cell-activated bone substitute, on a two-level large posterolateral spine fusion sheep model....

  11. Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile.

    Science.gov (United States)

    Rosen, J; Negro-Vilar, A

    2002-03-01

    A novel approach to the treatment of osteoporosis in men, and possibly women, is the development of selective androgen receptor modulators (SARMs) that can stimulate formation of new bone with substantially diminished proliferative activity in the prostate, as well as reduced virilizing activity in women. Over the last several years, we have developed a program to discover and develop novel, non-steroidal, orally-active selective androgen receptor modulators (SARMs) that provide improved therapeutic benefits and reduce risk and side effects. In recent studies, we have used a skeletally mature orchiectomized (ORX) male rat as an animal model of male hypogonadism for assessing the efficacy of LGD2226, a nonsteroidal, non-aromatizable, and non-5alpha-reducible SARM. We assessed the activity of LGD2226 on bone turnover, bone mass and bone strength, and also evaluated the effects exerted on classic androgen-dependent targets, such as prostate, seminal vesicles and muscle. A substantial loss of bone density was observed in ORX animals, and this loss was prevented by SARMs, as well as standard androgens. Biochemical markers of bone turnover revealed an early increase of bone resorption in androgen-deficient rats that was repressed in ORX animals treated with the oral SARM, LGD2226, during a 4-month treatment period. Differences in architectural properties and bone strength were detected by histomorphometric and mechanical analyses, demonstrating beneficial effects of LGD2226 on bone quality in androgen-deficient rats. Histomorphometric analysis of cortical bone revealed distinct anabolic activity of LGD2226 in periosteal bone. LGD2226 was able to prevent bone loss and maintain bone quality in ORX rats by stimulating bone formation, while also inhibiting bone turnover. LGD2226 also exerted anabolic activity on the levator ani muscle. Taken together, these results suggest that orally-active, non-steroidal SARMs may be useful therapeutics for both muscle and bone in elderly

  12. Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: a new type of cancer-host partnership?

    DEFF Research Database (Denmark)

    Levin Andersen, Thomas; Boissy, Patrice; Sondergaard, T E

    2007-01-01

    through fusion between myeloma cells and osteoclasts. In conclusion, malignant cells contribute significantly to the formation of bone-resorbing osteoclasts in multiple myeloma. Osteoclast-myeloma clone hybrids reflect a previously unrecognized mechanism of bone destruction in which malignant cells...

  13. Combined effects of soy isoflavone and fish oil on ovariectomy-induced bone loss in mice.

    Science.gov (United States)

    Uchida, Raina; Chiba, Hiroshige; Ishimi, Yoshiko; Uehara, Mariko; Suzuki, Kazuharu; Kim, Hyounju; Matsumoto, Akiyo

    2011-07-01

    Both soy isoflavone and n-3 polyunsaturated fatty acids are known to reduce the levels of bone-resorbing cytokines; however, the synergistic effects of these food ingredients have not been examined yet. This study was performed to elucidate the effect of concomitant intake of soy isoflavone and fish oil on bone mass in ovariectomized mice. Eight-week-old ddY female mice were subjected to ovariectomy (OVX) or sham surgery, and then fed an AIN-93G with safflower oil (So) as a control lipid source, isoflavone-supplemented safflower oil (So + I), fish oil instead of safflower oil (Fo) or isoflavone-supplemented fish oil (Fo + I) for 4 weeks. Femoral bone mineral density was significantly decreased by OVX; however, this decrease was inhibited by the intake of isoflavone and/or fish oil. Histomorphometric analyses showed that bone volume and trabecular thickness in the distal femoral trabecular bone were significantly lower in the So group than in the sham group, but those were restored in the Fo + I groups. The number of osteoclasts was significantly decreased by isoflavone intake. The increased rate of bone resorption after OVX was inhibited by isoflavone and/or fish oil. The serum concentration of tumor necrosis factor alpha was increased after OVX, but was significantly lower with the combination of isoflavone with fish oil than isoflavone or fish oil alone. The results of this study indicated that the intakes of soy isoflavone and/or fish oil might have ameliorating effects on bone loss due to OVX. Further, the concomitant intake of soy isoflavone and fish oil at a low dose showed better effects on cytokines related with bone resorption.

  14. Evaluation of poly-L-lactic acid and polyglycolic acid resorbable stents for repair of tracheomalacia in a porcine model.

    Science.gov (United States)

    Nalwa, S S; Hartig, G K; Warner, T; Connor, N P; Thielman, M J

    2001-11-01

    Poly-L-lactic acid and polyglycolic acid (PLPG) resorbable stents may offer a potential solution to the problem of tracheomalacia. Advantages of this material include its strength, its versatile shaping characteristics, and its resorbability, which would preclude surgical removal and allow for airway growth. The purpose of this pilot study was to examine the usefulness of PLPG stents for temporary external airway stenting of tracheomalacia in a porcine model. A severe tracheomalacia was created in 6 pigs by submucosal resection of segments of tracheal cartilage from 6 consecutive rings. The PLPG stent was then shaped to recreate the tracheal contour and sutured to the underlying airway. Endoscopic photodocumentation during spontaneous ventilation was obtained before and after reconstruction. After creation of the malacic tracheal segment, all animals developed stridor, retractions, and cyanosis during spontaneous ventilation. After repair, all animals were extubated without complication. All animals survived the follow-up period of 9 to 12 weeks without evidence of respiratory distress and with rapid weight gain. Repeat bronchoscopy showed no evidence of airway collapse during spontaneous ventilation. Tracheal measurements revealed growth of the stented segment with a mild narrowing within the repaired region. Histologic examination showed preservation of respiratory epithelium. These preliminary findings suggest that PLPG stents may serve a useful role in the surgical management of tracheomalacia.

  15. Esculetin attenuates receptor activator of nuclear factor kappa-B ligand-mediated osteoclast differentiation through c-Fos/nuclear factor of activated T-cells c1 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Jong Min; Park, Sun-Hyang; Cheon, Yoon-Hee; Ahn, Sung-Jun [Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Lee, Myeung Su [Division of Rheumatology, Department of Internal Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Oh, Jaemin, E-mail: jmoh@wku.ac.kr [Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Ju-Young, E-mail: kimjy1014@gmail.com [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2015-05-29

    Esculetin exerts various biological effects on anti-oxidation, anti-tumors, and anti-inflammation. However, the involvement of esculetin in the bone metabolism process, particularly osteoclast differentiation has not yet been investigated. In the present study, we first confirmed the inhibitory effect of esculetin on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. We then revealed the relationship between esculetin and the expression of osteoclast-specific molecules to elucidate its underlying mechanisms. Esculetin interfered with the expression of c-Fos and nuclear factor of activated T cell c1 (NFATc1) both at the mRNA and protein level with no involvement in osteoclast-associated early signaling pathways, suppressing the expression of various transcription factors exclusively expressed in osteoclasts such as tartrate-resistant acid phosphatase (Trap), osteoclast-associated receptor (Oscar), dendritic cell-specific transmembrane protein (Dcstamp), osteoclast stimulatory transmembrane protein (Ocstamp), cathepsin K, αvβ3 integrin, and calcitonin receptor (Ctr). Additionally, esculetin inhibited the formation of filamentous actin (F-actin) ring-positive osteoclasts during osteoclast differentiation. However, the development of F-actin structures and subsequent bone resorbing activity of mature osteoclasts, which are observed in osteoclast/osteoblast co-culture systems were not affected by esculetin. Taken together, our results indicate for the first time that esculetin inhibits RANKL-mediated osteoclastogenesis via direct suppression of c-Fos and NFATc1 expression and exerts an inhibitory effect on actin ring formation during osteoclastogenesis. - Highlights: • We first investigated the effects of esculetin on osteoclast differentiation and function. • Our data demonstrate for the first time that esculetin can suppress osteoclastogenesis in vitro. • Esculetin acts as an inhibitor of c-Fos and NFATc1 activation.

  16. Neutron activation analysis of medullar and cortical bone tissues from animals

    International Nuclear Information System (INIS)

    Takata, Marcelo Kazuo; Saiki, Mitiko

    2000-01-01

    In this work, neutron activation analysis was applied in the determination of the elements Ba, Br, Ca, Cl, Cr, Fe, K, Mg, Mn, Na, P, Rb, Sb, Sc, Sr and Zn present in animal bone tissues. The obtained results indicated a significant difference between the elemental concentrations present in medullar and cortical tissues. The results obtained for bone tissues from distinct animal species were also different. (author)

  17. Sr, Mg cosubstituted HA porous macro-granules: potentialities as resorbable bone filler with antiosteoporotic functions.

    Science.gov (United States)

    Landi, Elena; Uggeri, Jacopo; Medri, Valentina; Guizzardi, Stefano

    2013-09-01

    Porous macro-granules of nanostructured apatite with Ca ions partially cosubstituted with Mg and Sr ions in different ratios (SrMgHAs), were synthesized at 37°C and compared with Mg and/or Sr free apatites (MgHAs and HA). Strontium improved the Mg substitution extent in the apatite and the chemical-physical and thermal stability of the resulting cosubstituted apatite. Porous macro-granules of 400-600 micron with selected composition were tested for the ionic release in synthetic body fluid and the data were related with the results of preliminary cell investigation in vitro. As compared to the corresponding Sr-free granulate, the SrMgHA could be exploited to prolong the beneficial Mg release during the bone regeneration process. In addition the contemporary in situ supply of Sr, an antiosteoporotic and anticarie ion, could influence the quality of new hard tissues. The ionic multirelease created a more favorable environment for human osteoblasts, demonstrated by a proliferative effect for each dose tested in the range 0.1-10 mg/mL. Copyright © 2013 Wiley Periodicals, Inc.

  18. Deproteinized Bovine Bone Mineral or Autologous Bone at Dehiscence Type Defects at Implants Installed Immediately into Extraction Sockets: An Experimental Study in Dogs.

    Science.gov (United States)

    Pereira, Flavia Priscila; De Santis, Enzo; Hochuli-Vieira, Eduardo; de Souza Faco, Eduardo F; Pantani, Fabio; Salata, Luiz A; Botticelli, Daniele

    2016-06-01

    The aim of this study was to evaluate bone regeneration at surgically created dehiscence buccal defects at implants placed immediately into extraction sockets (IPIES) of small dimensions filled with autogenous bone or deproteinized bovine bone mineral (DBBM) associated with a collagen membrane. Eight Labrador dogs were used and implants were placed immediately into the extraction sockets of the second premolar. The buccal wall was subsequently removed to create a standardized defect, 4 mm wide coronally, 2 mm wide apically, and 6 mm high. Autogenous bone particles (AB) or DBBM granules were used to fill the defects. All surgical sites were subsequently covered by a resorbable collagen membrane and a non-submerged healing was allowed. After 4 months, the animals were euthanized and bone blocks harvested and processed for histomorphometric analysis. The bony crest at the buccal aspect (C) was located 2.3 ± 0.8 mm and 1.7 ± 0.7 mm apically to the implant shoulder (IS) at the AB and DBBM sites, respectively. The coronal levels of osseointegration at the buccal aspect (B) were located 2.7 ± 0.7 mm and 2.2 ± 1.0 mm apically to IS at the AB and DBBM sites, respectively. At the AB sites, the peri-implant mucosa was located 4.3 ± 0.9 mm, 4.7 ± 0.9 mm, and 2.0 ± 1.6 mm coronally to C, B, and IS, respectively. The corresponding values at the DBBM sites were 4.3 ± 0.6 mm, 4.8 ± 0.6 mm, and 2.5 ± 0.8 mm, respectively. No statistically significant differences were found. The treatment of surgically created buccal defects at IPIES sites using Bio-Oss® (Geistlich Biomaterials, Wolhusen, LU, Switzerland) or autogenous bone, concomitantly with a collagen membrane, engenders bone regeneration to a similar extent after 4 months of healing. © 2015 Wiley Periodicals, Inc.

  19. Use of cyanoacrylate as barrier in guided tissue regeneration in class II furcation defects

    Directory of Open Access Journals (Sweden)

    Carmen L Mueller Storrer

    2014-01-01

    Full Text Available The guided bone regeneration (GBR is a technique that uses resorbable and non-resorbable membranes in association with other filling biomaterials. GBR is one of the optional treatments for therapy of class II furcation defects. The current case report evaluates clinically and radiographically the use of the cyanoacrylate membrane (Glubran ®2 associated with organic bovine bone (GenOx for the treatment of vestibular class II furcation defect on the lower left molar. Conclusion: The GBR is an option in the treatment of vestibular class II furcation defects and cyanoacrylate surgical glue, acting as a mechanic barrier and providing an efficient stability for the graft.

  20. Neutron activation and track analysis of the newly found bones of the southern mammoths and dinosaurs

    International Nuclear Information System (INIS)

    Vasidov, A.; Osinskaya, N.S.; Saidullaev, B.J.; Akhmadshaev, A.

    2016-01-01

    The bones of southern mammoths and dinosaur had been discovered in the territory of Uzbekistan in 2005-2014. The main aim of the work was a study of profiles of radiogenic and some of elements in bones of mammoths and dinosaur, and the element comparisons with standard bones and its soils by instrumental neutron activation and track analysis. In bones of the mammoths and dinosaur were registered a high contents of uranium and rare earth elements by instrumental neutron activation analysis. The radon concentrations in samples were measured in isolated plastic chambers by solid state nuclear track detectors type of CR-39 within 35 days. The values of radon exhalation rates were determined very more in ancient bones than in standard bones and soils. (author)

  1. Bone metabolic activity in hyperostosis cranialis interna measured with {sup 18}F-fluoride PET

    Energy Technology Data Exchange (ETDEWEB)

    Waterval, Jerome J.; Dongen, Thijs M.A. van; Stokroos, Robert J.; Manni, Johannes J. [Maastricht University Medical Center, Department of Otorhinolaryngology and Head and Neck Surgery, Maastricht (Netherlands); Teule, Jaap G.J.; Kemerink, Gerrit J.; Brans, Boudewijn [Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Nieman, Fred H.M. [Maastricht University Medical Center, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht (Netherlands)

    2011-05-15

    {sup 18}F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves. The aim of this study is to compare standardised uptake values (SUVs) at different sites in order to quantify bone metabolism in the affected anatomical regions in HCI patients. Nine affected family members, seven non-affected family members and nine non-HCI non-family members underwent {sup 18}F-fluoride PET/CT scans. SUVs were systematically measured in the different regions of interest: frontal bone, sphenoid bone, petrous bone and clivus. Moreover, the average {sup 18}F-fluoride uptake in the entire skull was measured by assessing the uptake in axial slides. Visual assessment of the PET scans of affected individuals was performed to discover the process of disturbed bone metabolism in HCI. {sup 18}F-Fluoride uptake is statistically significantly higher in the sphenoid bone and clivus regions of affected family members. Visual assessment of the scans of HCI patients is relevant in detecting disease severity and the pattern of disturbed bone metabolism throughout life. {sup 18}F-Fluoride PET/CT is useful in quantifying the metabolic activity in HCI and provides information about the process of disturbed bone metabolism in this specific disorder. Limitations are a narrow window between normal and pathological activity and the influence of age. This study emphasises that {sup 18}F-fluoride PET/CT may also be a promising diagnostic tool for other metabolic bone disorders, even those with an indolent course. (orig.)

  2. Trace aluminium determination and sampling problems of archeological bone employing destructive neutron activation analysis

    International Nuclear Information System (INIS)

    Blotcky, A.J.; Rack, E.P.; Recker, R.R.; Leffler, J.A.; Teitelbaum, S.

    1978-01-01

    A destructive neutron activation analysis procedure was developed for determining trace aluminium content in bone. The method is based on a carefully planned sample preparation, irradiation at a neutron flux for 3.1x10 11 nxcm -2 xs -1 for 5 minutes, and chemical separation based on ion exchange. It was found that bone samples soaked in aluminium containing soil gave highly elevated aluminium values as a result of the aluminium adsorption into the bone matrix. The maximum aluminium content values for prehistoric bones are larger than those of modern bones and comparable to aluminium levels present in bone from renal patients. (T.G.)

  3. 3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep

    DEFF Research Database (Denmark)

    Ding, Ming; Snoek Henriksen, Susan; Martinetti, Roberta

    2017-01-01

    allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while......, bone formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016....

  4. Activated protein C (APC) can increase bone anabolism via a protease-activated receptor (PAR)1/2 dependent mechanism.

    Science.gov (United States)

    Shen, Kaitlin; Murphy, Ciara M; Chan, Ben; Kolind, Mille; Cheng, Tegan L; Mikulec, Kathy; Peacock, Lauren; Xue, Meilang; Park, Sang-Youel; Little, David G; Jackson, Chris J; Schindeler, Aaron

    2014-12-01

    Activated Protein C (APC) is an anticoagulant with strong cytoprotective properties that has been shown to promote wound healing. In this study APC was investigated for its potential orthopedic application using a Bone Morphogenetic Protein 2 (rhBMP-2) induced ectopic bone formation model. Local co-administration of 10 µg rhBMP-2 with 10 µg or 25 µg APC increased bone volume at 3 weeks by 32% (N.S.) and 74% (pAPC are largely mediated by its receptors endothelial protein C receptor (EPCR) and protease-activated receptors (PARs). Cultured pre-osteoblasts and bone nodule tissue sections were shown to express PAR1/2 and EPCR. When pre-osteoblasts were treated with APC, cell viability and phosphorylation of ERK1/2, Akt, and p38 were increased. Inhibition with PAR1 and sometimes PAR2 antagonists, but not with EPCR blocking antibodies, ameliorated the effects of APC on cell viability and kinase phosphorylation. These data indicate that APC can affect osteoblast viability and signaling, and may have in vivo applications with rhBMP-2 for bone repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  5. Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients with active Crohn's disease: a prospective study.

    Science.gov (United States)

    Ryan, B M; Russel, M G V M; Schurgers, L; Wichers, M; Sijbrandij, J; Stockbrugger, R W; Schoon, E

    2004-10-15

    Patients with Crohn's disease are at increased risk of osteoporosis. Disease activity and circulating proinflammatory cytokines are thought to play a role in this process. Infliximab, a chimaeric antitumour necrosis factor-alpha antibody is effective in the treatment of Crohn's disease. The aim of this study was to investigate the impact of treatment with infliximab on bone turnover in Crohn's disease patients. This was a prospective trial. Twenty-four patients with active Crohn's disease were treated with infliximab (5 mg/kg). Bone markers were assayed pre- and post-treatment. Bone formation was measured using serum bone-specific alkaline phosphatase and total osteocalcin and bone resorption using serum N-telopeptide cross-linked type 1 collagen. Infliximab therapy caused a significant increase in both markers of bone formation in patients with active Crohn's disease. No significant change in the bone resorption marker serum N-telopeptide cross-linked type 1 was found. Infliximab therapy had a significant beneficial effect on bone metabolism in patients with active Crohn's disease. These findings further support the theory that active ongoing inflammation and high levels of circulating cytokines play a pivotal role in the pathogenesis of bone loss in patients with Crohn's disease.

  6. Three-dimensional analysis of bone remodeling following ridge augmentation of compromised extraction sockets in periodontitis patients: A randomized controlled study.

    Science.gov (United States)

    Aimetti, Mario; Manavella, Valeria; Corano, Lisa; Ercoli, Elena; Bignardi, Cristina; Romano, Federica

    2018-02-01

    The aim of this study was to analyze linear and volumetric hard tissue changes in severely resorbed alveolar sockets after ridge augmentation procedure and to compare them with spontaneous healing using three-dimensional cone beam computed tomography (CBCT). Thirty patients (mean age 53.2 ± 6.3 years) requiring tooth extraction for advanced periodontitis were randomly allocated to test and control groups. The test sites were grafted using a collagenated bovine-derived bone (DBBM-C) covered with a collagen membrane, while control sites had spontaneous healing. Both groups healed by secondary intention. Linear and volumetric measurements were taken on superimposed CBCT images obtained after tooth extraction and 12 months later. Greater horizontal shrinkage, localized mainly in the crestal zone, was observed in the control group (4.92 ± 2.45 mm) compared to the test group (2.60 ± 1.24 mm). While both groups presented a rebuilding of the buccal wall, it was most pronounced in the grafted sockets (2.50 ± 2.12 mm vs. 0.51 ± 1.02 mm). A significant difference was also registered in the percentage of volume loss between grafted and non-grafted sites (9.14% vs. 35.16%, p-value sockets with extensive buccal bone deficiencies undergo significant three-dimensional volumetric alterations following natural healing. The immediate application of a slow-resorbing xenograft with a covering collagen membrane seems to be effective in improving alveolar ridge shape and dimensions, thus potentially reducing the need for adjunctive regenerative procedures at the time of implant placement. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin

    Directory of Open Access Journals (Sweden)

    Jingru Meng

    2016-04-01

    Full Text Available Glucagon-like peptide 1 (GLP-1 plays an important role in regulating bone remodeling, and GLP-1 receptor agonist shows a positive relationship with osteoblast activity. However, GLP-1 receptor is not found in osteoblast, and the mechanism of GLP-1 receptor agonist on regulating bone remodeling is unclear. Here, we show that the GLP-1 receptor agonist exendin-4 (Ex-4 promoted bone formation and increased bone mass and quality in a rat unloading-induced bone loss model. These functions were accompanied by an increase in osteoblast number and serum bone formation markers, while the adipocyte number was decreased. Furthermore, GLP-1 receptor was detected in bone marrow stromal cells (BMSCs, but not in osteoblast. Activation of GLP-1 receptor by Ex-4 promoted the osteogenic differentiation and inhibited BMSC adipogenic differentiation through regulating PKA/β-catenin and PKA/PI3K/AKT/GSK3β signaling. These findings reveal that GLP-1 receptor regulates BMSC osteogenic differentiation and provide a molecular basis for therapeutic potential of GLP-1 against osteoporosis.

  8. Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA and Langerhans cell histiocytosis (LCH are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC, and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.

  9. Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity

    Science.gov (United States)

    Intini, Giuseppe; Nyman, Jeffry S.

    2015-01-01

    Bone fractures remain a serious health burden and prevention and enhanced healing of fractures has been obtained by augmenting either BMP or Wnt signaling. However, whether BMP and Wnt signaling are both required or are self-sufficient for anabolic and fracture healing activities has never been fully elucidated. Mice haploinsufficient for Dkk1 (Dkk1+/−) exhibit a high bone mass phenotype due to an up-regulation of canonical Wnt signaling while mice lacking Bmp2 expression in the limbs (Bmp2c/c;Prx1::cre) succumb to spontaneous fracture and are unable to initiate fracture healing; combined, these mice offer an opportunity to examine the requirement for activated BMP signaling on the anabolic and fracture healing activity of Wnts. When Dkk1+/− mice were crossed with Bmp2c/c;Prx1::cre mice, the offspring bearing both genetic alterations were unable to increase bone mass and heal fractures, indicating that increased canonical Wnt signaling is unable to exploit its activity in absence of Bmp2. Thus, our data suggest that BMP signaling is required for Wnt-mediated anabolic activity and that therapies aimed at preventing fractures and fostering fracture repair may need to target both pathways for maximal efficacy. PMID:25603465

  10. Lifelong physical activity in maintaining bone strength in older men and women of the Age, Gene/Environment Susceptibility-Reykjavik Study.

    Science.gov (United States)

    Rianon, N J; Lang, T F; Sigurdsson, G; Eiriksdottir, G; Sigurdsson, S; Garcia, M; Pajala, S; Koster, A; Yu, B; Selwyn, B J; Taylor, W C; Kapadia, A S; Gudnason, V; Launer, L J; Harris, T B

    2012-09-01

    We examined if lifelong physical activity is important for maintaining bone strength in the elderly. Associations of quantitative computerized tomography-acquired bone measures (vertebral and femoral) and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES-Reykjavik Study. Results conclude lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health later in life. Skeletal loading is thought to modulate the loss of bone in later life, and physical activity is a chief means of affecting bone strength by skeletal loading. Despite much discussion regarding lifelong versus early adulthood physical activity for preventing bone loss later in life, inconsistency still exists regarding how to maintain bone mass later in life (≥65 years). We examined if lifelong physical activity is important for maintaining bone strength in the elderly. The associations of quantitative computerized tomography-acquired vertebral and femoral bone measures and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES-Reykjavik Study. Our findings conclude that lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health in the elderly.

  11. Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs.

    Science.gov (United States)

    Seymour, Roger S; Smith, Sarah L; White, Craig R; Henderson, Donald M; Schwarz-Wings, Daniela

    2012-02-07

    The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat.

  12. Usage of demineralized bone powder in dental implant surgery

    International Nuclear Information System (INIS)

    Chang Joon Yim

    1999-01-01

    While there is much concern in the dental community about the risk of disease transfer with processed bone a] iografts, there has never been a case of disease transfer with DFDB. Exclusionary techniques and chemical processing of the allogeneic bone has rendered these grafts safe for human implantation. The literature indicates that there has been considerable interest in the biology and applied science of osteoinduction. The accumulated evidence supports the concept of cartilage and bone cell differentiation induced by a unique bone motphogenetic protein (BMP). Currently clinical usage has been focused on the alveolar bone defects associated with the dental implant surgery, which has become one of the most important areas in dental outpatient clinic. Increased application of the endosseous dental implant system results in a lot of demands to regenerate the alveolar bone defects around the dental implants. Anderegg et al.(1991) reported the excellent results from the combination of DFDB powder and expanded PTFE (polytetrafluorethylene) membranes. Since 1980 the author experienced the human DFDB powders for the oral and maxillofacial surgery and the dental implant surgery. Yim and Kim(1993) evaluated 93 surgical sites where DFDB was used and found 96.7% of success rates at re-entry surgery. Mellonig and Triplett (1993) reported 97% of success rates, and Gelb (1993) obtained 98% of success rates. Fugazzotto (1994) placed 59 dental implants at the time of sinus lifts with the composite graft of DFDB and resorbable tricalcium phosphate and none of implants was lost on uncovering and only one was lost while functioning. Yim (1994) placed 44 dental implants at the time of sinus lifts with DFDB, and none of implants was lost on uncovering. Zinner and Small (1996) placed 215 dental implants at the time of sinus lifts (52 sinuses) with the composite graft of DFDB, and other materials, 3 implants of which were failed on uncovering. To date, maxillary sinus lift graft with

  13. Calcaneal Quantitative Ultrasound Indicates Reduced Bone Status Among Physically Active Adult Forager-Horticulturalists.

    Science.gov (United States)

    Stieglitz, Jonathan; Madimenos, Felicia; Kaplan, Hillard; Gurven, Michael

    2016-03-01

    Sedentary lifestyle contributes to osteoporosis and fragility fracture risks among modern humans, but whether such risks are prevalent in physically active preindustrial societies with lower life expectancies is unclear. Osteoporosis should be readily observable in preindustrial societies if it was regularly experienced over human history. In this study of 142 older adult Tsimane forager-horticulturalists (mean age ± SD, 62.1 ± 8.6 years; range, 50 to 85 years; 51% female) we used calcaneal quantitative ultrasonography (qUS) to assess bone status, document prevalence of adults with reduced bone status, and identify factors (demographic, anthropometric, immunological, kinesthetic) associated with reduced bone status. Men (23%) are as likely as women (25%) to have reduced bone status, although age-related decline in qUS parameters is attenuated for men. Adiposity and fat-free mass positively co-vary with qUS parameters for women but not men. Leukocyte count is inversely associated with qUS parameters controlling for potential confounders; leukocyte count is positively correlated within adults over time, and adults with persistently low counts have higher adjusted qUS parameters (6% to 8%) than adults with a high count. Reduced bone status characteristic of osteoporosis is common among active Tsimane with minimal exposure to osteoporosis risk factors found in industrialized societies, but with energetic constraints and high pathogen burden. © 2015 American Society for Bone and Mineral Research.

  14. Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases.

    Science.gov (United States)

    Wan, Xinhai; Corn, Paul G; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W; Efstathiou, Eleni; Li Ning Tapia, Elsa M; Tapia, Elsa M Li-Ning; Zurita, Amado J; Aparicio, Ana; Ravoori, Murali K; Vazquez, Elba S; Robinson, Dan R; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M; Logothetis, Christopher J; Navone, Nora M

    2014-09-03

    Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell-bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in serum prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. Copyright © 2014, American Association for the Advancement of Science.

  15. Relationship of Physical Activity Type, Nutrition, and Bone Mineral Density in Korean Adolescents

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    Yong Hwan Kim

    2017-10-01

    Full Text Available Bone density reaches its peak in the mid-20s, and it manifests as osteoporosis and osteopenia with aging. Bone density is affected by body mass index, muscle mass, nutritional calcium and vitamin D, various lifestyles, physical activity level, and high level of strength. The purpose of this study was to investigate the difference in diet and bone density according to physical activity level in growing male and female adolescents. This study involved 646 male and 581 female adolescents using data from the Korea National Health and Nutrition Examination in 2009-2011. The measurement of bone density consisted of dual-energy X-ray absorptiometry, and they were classified into low, middle, and high groups at different ages based on total bone mineral density. The Korean version of the International Physical Activity Questionnaire by the World Health Organization was used to measure physical activity level, and a survey regarding strength exercise and stretching was conducted. In the nutritional survey, data from a 24h recall were analyzed. One-way analysis of variance and chi-square test were conducted to examine the significance of any differences present. Even though there was no difference among groups in both males and females, there was a significant difference in weight (p0.05. In males, the high group showed significantly higher calorie intake (p=0.032, protein (p=0.015, calcium (p=0.043, and phosphorus (p=0.013 compared with the low group according to nutrition intake. In terms of physical activity level, there was significant a difference as the proportion of strength exercise more than 3 times a week was 18.1% and 27.2% in the low and high groups, respectively in males (p=0.046, and was 1.0% and 6.1% respectively in females (p=0.014. The proportion of high-intensity exercise 6-7 times a week also showed a significant difference as the low, middle, and high groups showed 5.1%, 5.5%, and 14.1%, respectively (p<0.001. Among adolescents, bone

  16. Evaluation of 99mTc-MDP bone imaging in bone transplantation

    International Nuclear Information System (INIS)

    Liu Sheng; Lu Bin; Chen Shaoxiong

    1995-01-01

    Radionuclide bone imaging was performed to evaluate bone metabolic activity after transplantation with coral combined autologous red marrow and the single coral group. The result was also compared with histological and X-ray examination. This finding revealed that 99m Tc-MDP concentration in the area of the transplanted bone changed dynamically and reached its maximum in 12 weeks following operation and showed various bone metabolic activities with different grafting materials. Clinical application showed that three phase bone imaging could evaluate the blood supply and activity of growing bone of the graft two months earlier than X-ray examination. It was considered that non-accumulation of 99m Tc-MDP in grafted area was a reliable indication of failure in transplantation one month after operation

  17. The relationship between BPAQ-derived physical activity and bone density of middle-aged and older men.

    Science.gov (United States)

    Bolam, K A; Beck, B R; Adlard, K N; Skinner, T L; Cormie, P; Galvão, D A; Spry, N; Newton, R U; Taaffe, D R

    2014-11-01

    The bone-specific physical activity questionnaire (BPAQ) accounts for activities that affect bone but has not been used in studies with older adults. Relationships exist between the BPAQ-derived physical activity and bone density in healthy middle-aged and older men but not men with prostate cancer. Disease-related treatments detrimental to bone should be considered when administering the BPAQ. The bone-specific physical activity questionnaire (BPAQ) was developed to account for bone-specific loading. In this retrospective study, we examined the relationship between BPAQ-derived physical activity and bone mineral density (BMD) in middle-aged and older men with and without prostate cancer. Two groups, 36 healthy men and 69 men with prostate cancer receiving androgen suppression therapy (AST), completed the BPAQ and had whole body, total hip, femoral (FN) and lumbar spine BMD assessed by dual-energy X-ray absorptiometry. Past (pBPAQ), current (cBPAQ) and total BPAQ (tBPAQ) scores for the healthy men were related to FN BMD (pBPAQ r = 0.36, p = 0.030; cBPAQ r s = 0.35, p = 0.034; tBPAQ r = 0.41, p = 0.014), and pBPAQ and tBPAQ were related to total hip (r s = 0.35, p = 0.035 and r s = 0.36, p = 0.029, respectively) and whole body BMD (r s = 0.44, p = 0.007 and r s = 0.45, p = 0.006, respectively). In men with prostate cancer, the BPAQ was not significantly associated with BMD. In stepwise regression analyses, body mass and tBPAQ predicted 30 % of the variance in total hip BMD (p = 0.003), cBPAQ predicted 14 % of the variance in FN BMD (p = 0.002), and body mass, age and tBPAQ predicted 47% of the variance in whole body BMD (p men. In men with prostate cancer, the BPAQ was not an independent predictor of BMD. Although BPAQ-derived estimates of physical activity are related to bone status in healthy middle-aged and older men, the adverse effect of AST on bone appears to obscure this relationship in men

  18. Absorbed dose to active red bone marrow from diagnostic and therapeutic uses of radiation

    International Nuclear Information System (INIS)

    Solomon, S.B.

    1980-06-01

    The bone-marrow dose arising from radiological procedures as carried out in Australia have been determined as part of a survey of population doses. This paper describes the method of calculation of the radiation doses to the active bone marrow from diagnostic radiography, fluoroscopy and radiotherapy. The results of the calculations are compared with the results of other models of bone-marrow dose for a number of diagnostic X-ray procedures

  19. Cartilage and bone neoformation in rabbit carotid bifurcation aneurysms after endovascular coil embolization

    Directory of Open Access Journals (Sweden)

    H Plenk

    2008-11-01

    Full Text Available Occurrence and histomorphology of cartilage and bone neoformations was retrospectively evaluated in rabbit experimental aneurysms after endovascular coil embolization. During product development, 115 carotid bifurcation aneurysms were treated with hydrogel-containing devices (HydroCoil®, n=77; HydroSoft®, n=28; prototype Hydrogel-only, n=10; MicroVentionTerumo, Aliso Viejo, CA. Additional 29 aneurysms were treated with standard (n=22 or with degradable polymer-covered (n=7 platinum coils. After 4 to 52 weeks, the retrieved aneurysms were methylmethacrylate embedded, and ground sections were surface-stained with Rapid Bone Stain and Giemsa solution. Cartilage and/or bone tissue was assessed by light microscopy; respective tissue areas in the aneurysms were determined by computerized histomorphometry. Cartilage neoformation was observed from 26 to 52 weeks. Single chondrocytes to hyaline or fibrous cartilage areas, occupying up to 29% of the aneurysm cavity, were found in 6 aneurysms, treated with HydroCoil (n=4, Hydrogel-only (n=1, and resorbable polymer (n=1 devices. Chondral ossification associated cartilage neoformation in 2 of these 4 HydroCoil-treated aneurysms. Membranous woven and lamellar bone ossicles were observed from 13 to 52 weeks in 7 aneurysms, treated with HydroCoil (n=3 and platinum coil (n=4 devices. Altogether, cartilage and/or bone neoformation was observed in 13 (9% of 144 rabbit bifurcation aneurysms treated with various embolic devices. Incidence was low until 26 weeks, but increased at 52 weeks in both, HydroCoil and standard platinum coil treated aneurysms. As the neoformations were predominantly located in proximity to the aneurysm neck, they could be related to the long-term mechanobiology of cell differentiation during fibrovascular healing of blood flow-exposed embolized aneurysms.

  20. Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

    Science.gov (United States)

    Chung, Hwa-Jin; Kyung Kim, Won; Joo Park, Hyen; Cho, Lan; Kim, Me-Riong; Kim, Min Jeong; Shin, Joon-Shik; Ho Lee, Jin; Ha, In-Hyuk; Kook Lee, Sang

    2016-02-17

    Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Assessment of activated porous granules on implant fixation and early bone formation in sheep

    Directory of Open Access Journals (Sweden)

    Ming Ding

    2016-04-01

    Conclusion: In conclusion, despite nice bone formation and implant fixation in all groups, bioreactor activated graft material did not convincingly induce early implant fixation similar to allograft, and neither bioreactor nor by adding BMA credited additional benefit for bone formation in this model.

  2. Denosumab for bone diseases: translating bone biology into targeted therapy.

    Science.gov (United States)

    Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

    2011-12-01

    Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

  3. Preliminary focus on the mechanical and antibacterial activity of a PMMA-based bone cement loaded with gold nanoparticles

    Directory of Open Access Journals (Sweden)

    T. Russo

    2017-09-01

    As reported in the literature, the stress distribution may be altered in bones after the implantation of a total joint prosthesis. Some scientific works have also correlated uncemented TKA to a progressive decrease of bone density below the tibial component. Antibiotic-loaded bone cements are commonly employed in conjunction with systemic antibiotics to treat infections. Furthermore, nanoparticles with antimicrobial activity have been widely analysed. Accordingly, the current research was focused on a preliminary analysis of the mechanical and antibacterial activity of a PMMA-based bone cement loaded with gold nanoparticles. The obtained results demonstrated that nanocomposite cements with a specific concentration of gold nanoparticles improved the punching performance and antibacterial activity. However, critical aspects were found in the optimization of the nanocomposite bone cement.

  4. Diversity of activity participation determines bone mineral content in the lower limbs of pre-pubertal children with developmental coordination disorder.

    Science.gov (United States)

    Fong, S S M; Vackova, D; Choi, A W M; Cheng, Y T Y; Yam, T T T; Guo, X

    2018-04-01

    This study examined the relationships between activity participation and bone mineralization in children with developmental coordination disorder. Limited participation in physical, recreational, social, and skill-based and self-improvement activities contributed to lower bone mineral content. For improved bone health, these children should participate in a variety of activities, not only physical activities. Limited activity participation in children with developmental coordination disorder (DCD) may have a negative impact on bone mineral accrual. The objectives of this study were to compare bone mineralization and activity participation patterns of pre-pubertal children with DCD and those with typical development, and to determine the association between activity participation patterns and bone mineralization in children with DCD. Fifty-two children with DCD (mean age = 7.51 years) and 61 children with typical development (mean age = 7.22 years) participated in the study. Appendicular and total body (less head) bone mineral content (BMC) and bone mineral density (BMD) were evaluated by a whole-body dual-energy X-ray absorptiometry scan. Activity participation patterns were assessed using the Children's Assessment of Participation and Enjoyment (CAPE) questionnaire. Children with DCD had lower appendicular and total body BMCs and BMDs than children with typical development overall (p accounting for the effects of age, sex, height, lean mass, and fat mass, the total activity diversity score remained independently associated with leg BMC in children with DCD, explaining 5.1% of the variance (p = 0.030). However, the physical activity diversity score was no longer associated with leg BMC (p = 0.090). Diversity of activity participation and bone mineralization were lower in pre-pubertal children with DCD. Decreased total activity participation diversity was a contributing factor to lower BMC in the legs of children with DCD.

  5. Sports activities and endurance capacity of bone tumor patients after rotationplasty.

    Science.gov (United States)

    Hillmann, Axel; Weist, Roger; Fromme, Albert; Völker, Klaus; Rosenbaum, Dieter

    2007-07-01

    To investigate the preferred types of sports activities of patients with rotationplasty and to measure their physiologic performance characteristics through treadmill ergometry. Cross-sectional, descriptive analysis and repeated measures of different velocities. Biomechanics research laboratory. Patients (n=61) with rotationplasty after bone tumor surgery, 30 of whom participated in a functional trial (treadmill), and a control group (n=20). Not applicable. Patients' participation in sports compared with that of the healthy population, treadmill performance at 2 or 3 different speeds, heart rate, lactate accumulation, oxygen consumption, ventilatory equivalent, efficiency, respiratory minute volume, and respiratory quotient. High activity in sports participation (85%) in most common sports (8 competitive, 17 sports club members, the remaining subjects were recreational athletes). At the same treadmill speed, lactate accumulation and all cardiorespiratory functions were higher in rotationplasty patients than in the control group. Patients can re-engage in a high level of physical activity after rotationplasty for bone tumor treatment. This physical activity is necessary if patients want to maintain or improve a desired level of sports activity.

  6. Status of bone mineral content and body composition in boys engaged in intensive physical activity

    Directory of Open Access Journals (Sweden)

    Madić Dejan

    2010-01-01

    Full Text Available Background/Aim. It is well known that physical activity has an anabolic effect on bone tissue. But there is a lack of information about the effect of intensive physical activity in childhood, particularly at the prepubertal stage. To examine the influence of training on body composition and bone mineral density we have studied a group of prepubertal soccer players as well as a group of inactive prepubertal boys at the starting phase of their peak bone mass acquisition. Methods. A total of 62 healthy prepubertal boys took part in this study. They were divided into two groups. The first one consisted of 32 soccer players (aged 10.7 ± 0.5 years, who had been playing football for at least 1 year (10-15 h per week. The second group a control group 30 boys (aged 11.2 ± 0.7 years doing 1.5 h per week physical activity at school. Body composition was assessed by a Body Fat Analyzer 'BES 200 Z'. Bone mineral density measurements of the left and the right calcaneus were done by using ultrasound densitometer 'Sahara' (Hologic, Inc., MA, USA. Results. There were significant differences between soccer players and the control group in fat mass (p = 0.01. Besides, a significant difference was determined between the group of athletes and the control group in bone mineral density of both calcaneal bones (p = 0.01. Conclusion. The results of this study confirm the significant effects of physical activity on reducing body mass and increasing bone density. Considering that football training can be very easily implemented in the broader population of children and young people, which does not apply to many other sports, it should be used more in the prevention of obesity and osteoporosis.

  7. Prostate Cancer Cell–Stromal Cell Cross-Talk via FGFR1 Mediates Antitumor Activity of Dovitinib in Bone Metastases

    Science.gov (United States)

    Wan, Xinhai; Corn, Paul G.; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W.; Efstathiou, Eleni; Li-Ning Tapia, Elsa M.; Zurita, Amado J.; Aparicio, Ana; Ravoori, Murali K.; Vazquez, Elba S.; Robinson, Dan R.; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K.; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M.; Logothetis, Christopher J.; Navone, Nora M.

    2015-01-01

    Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell–bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. PMID:25186177

  8. The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development.

    Science.gov (United States)

    Lappe, Joan M; Watson, Patrice; Gilsanz, Vicente; Hangartner, Thomas; Kalkwarf, Heidi J; Oberfield, Sharon; Shepherd, John; Winer, Karen K; Zemel, Babette

    2015-01-01

    Childhood and adolescence are critical periods of bone mineral content (BMC) accrual that may have long-term consequences for osteoporosis in adulthood. Adequate dietary calcium intake and weight-bearing physical activity are important for maximizing BMC accrual. However, the relative effects of physical activity and dietary calcium on BMC accrual throughout the continuum of pubertal development in childhood remains unclear. The purpose of this study was to determine the effects of self-reported dietary calcium intake and weight-bearing physical activity on bone mass accrual across the five stages of pubertal development in a large, diverse cohort of US children and adolescents. The Bone Mineral Density in Childhood study was a mixed longitudinal study with 7393 observations on 1743 subjects. Annually, we measured BMC by dual-energy X-ray absorptiometry (DXA), physical activity and calcium intake by questionnaire, and pubertal development (Tanner stage) by examination for up to 7 years. Mixed-effects regression models were used to assess physical activity and calcium intake effects on BMC accrual at each Tanner stage. We found that self-reported weight-bearing physical activity contributed to significantly greater BMC accrual in both sexes and racial subgroups (black and nonblack). In nonblack males, the magnitude of the activity effect on total body BMC accrual varied among Tanner stages after adjustment for calcium intake; the greatest difference between high- and low-activity boys was in Tanner stage 3. Calcium intake had a significant effect on bone accrual only in nonblack girls. This effect was not significantly different among Tanner stages. Our findings do not support differential effects of physical activity or calcium intake on bone mass accrual according to maturational stage. The study demonstrated significant longitudinal effects of weight-bearing physical activity on bone mass accrual through all stages of pubertal development. © 2014 American

  9. Antiosteoporotic Activity of Dioscorea alata L. cv. Phyto through Driving Mesenchymal Stem Cells Differentiation for Bone Formation

    Directory of Open Access Journals (Sweden)

    Kang-Yung Peng

    2011-01-01

    Full Text Available The aim of this study was to evaluate the effect of an ethanol extract of the rhizomes of Dioscorea alata L. cv. Phyto, Dispo85E, on bone formation and to investigate the mechanisms involved. Our results showed that Dispo85E increased the activity of alkaline phosphatase (ALP and bone nodule formation in primary bone marrow cultures. In addition, Dispo85E stimulated pluripotent C3H10T1/2 stem cells to differentiate into osteoblasts rather than adipocytes. Our in vivo data indicated that Dispo85E promotes osteoblastogenesis by increasing ALP activity and bone nodule formation in both intact and ovariectomized (OVX mice. Microcomputed tomography (μCT analysis also showed that Dispo85E ameliorates the deterioration of trabecular bone mineral density (tBMD, trabecular bone volume/total volume (BV/TV, and trabecular bone number (Tb.N in OVX mice. Our results suggested that Dispo85E is a botanical drug with a novel mechanism that drives the lineage-specific differentiation of bone marrow stromal cells and is a candidate drug for osteoporosis therapy.

  10. Super bone scans on bone scintigraphy in patients with metastatic bone tumor

    International Nuclear Information System (INIS)

    Morita, Koichi; Fukunaga, Masao; Otsuka, Nobuaki

    1988-01-01

    Eight patients with malignant tumor (3 with gastric cancer, 4 with prostatic cancer, 1 with transitional cell carcinoma), which showed diffusely increased uptake of 99m Tc labelled phosphorous compound in axial skeleton (''Super Bone Scan'') on bone scintigraphy were clinically studied. No relationship with its histological type of the tumor was recognized. All cases revealed extremely high serum ALP concentration, which might reflect increased osteoblastic activity. Furthermore, on bone roentgenograms all cases showed predominantly osteosclerotic change in the metastatic bones, while some did locally osteolytic change. In three cases with gastric cancer, although they had diffuse skeletal metastases, two had no evidence of liver metastases. Thus, it seemed that clinical study of patients with ''Super Bone Scan'' was interesting to evaluate the mechanism of accumulation of 99m Tc labelled phosphorous compound to bone and bone metabolism, and the pathophysiology in the pathway of bone metastases. (author)

  11. Effect of RGD Peptide-Coated TiO2 Nanotubes on the Attachment, Proliferation, and Functionality of Bone-Related Cells

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    Seunghan Oh

    2013-01-01

    Full Text Available The purpose of this research was to characterize an Arg-Gly-Asp (RGD peptide immobilized on TiO2 nanotubes. In addition, we investigated the effects of the RGD peptide-coated TiO2 nanotubes on the cellular response, proliferation, and functionality of osteogenic-induced human mesenchymal stem cells (hMSCs, which are osteoclasts that have been induced by bone marrow macrophages. The RGD peptide was grafted covalently onto the surface of TiO2 nanotubes based on the results of SEM, FT-IR, and XPS. Furthermore, the RGD peptide promoted the initial attachment and proliferation of the hMSCs, regardless of the size of the TiO2 nanotubes. However, the RGD peptide did not prominently affect the osteogenic functionality of the hMSCs because the peptide suppressed hMSC motility associated with osteogenic differentiation. The result of an in vitro osteoclast test showed that the RGD peptide accelerated the initial attachment of preosteoclasts and the formation of mature osteoclasts, which could resorb the bone matrix. Therefore, we believe that an RGD coating on TiO2 nanotubes synthesized on Ti implants might not offer significant acceleration of bone formation in vivo because osteoblasts and osteoclasts reside in the same compartment.

  12. Dual mode antibacterial activity of ion substituted calcium phosphate nanocarriers for bone infections

    Directory of Open Access Journals (Sweden)

    Sampath Kumar eT.S.

    2015-05-01

    Full Text Available Nanotechnology has tremendous potential for the management of infectious diseases caused by multi-drug resistant (MDR bacteria, through the development of newer antibacterial materials and efficient modes of antibiotic delivery. Calcium phosphate (CaP bioceramics are commonly used as bone substitutes due to their similarity to bone mineral and are widely researched upon for the treatment of bone infections associated with bone loss. CaPs can be used as local antibiotic delivery agents for bone infections and can be substituted with antibacterial ions in their crystal structure to have a wide spectrum, sustained antibacterial activity even against drug resistant bacteria. In the present work, a dual mode antibiotic delivery system with antibacterial ion substituted calcium deficient hydroxyapatite (CDHA nanoparticles has been developed. Antibacterial ions such as zinc, silver and strontium have been incorporated into CDHA at concentrations of 6 at. %, 0.25-0.75 at. % and 2.5-7.5 at. % respectively. The samples were found to be phase pure, acicular nanoparticles of length 40-50 nm and width 5-6 nm approximately. The loading and release profile of doxycycline, a commonly used antibiotic, was studied from the nanocarriers. The drug release was studied for five days and the release profile was influenced by the ion concentrations. The release of antibacterial ions was studied over a period of 21 days. The ion substituted CDHA samples were tested for antibacterial efficacy on S.aureus and E.coli by MIC/MBC studies and time-kill assay. AgCDHA and ZnCDHA showed high antibacterial activity against both bacteria while SrCDHA was weakly active against S.aureus. Present study shows that the antibiotic release can provide the initial high antibacterial activity and the sustained ion release can provide a long-term antibacterial activity. Such dual mode antibiotic and antibacterial ion release offers an efficient and potent way to treat an incumbent drug

  13. In vivo analysis of bone calcium by local neutron activation of the hand. Results osteoporotic and hemodialysed patients

    International Nuclear Information System (INIS)

    Maziere, B.; Kuntz, D.; Comar, D.

    1978-01-01

    Neutron activation analysis can be used to measure the total bone mass or simply the calcium mass or concentration of a bone segment, for example the hand bones or vertebrae. For a number of reason, dosimetric, technological but especially physiophatological we decided to use local activation technique. In generalized demineralising one diseases, particularly osteoporosis, the calcium content variations of one segment are in fast comparable to those of another, and more generally to the mineral content variations of the whole skeleton. It is true that ideally we should measure the mineral content of the lumbar vertebrae where the metabolic activity is especially high, and where damage may occur sooner or in any case is detected earlier in osteoporosis. However neutron irradiation of the vertebrae meets with certain technical problems and may also present difficulties in the interpretation of results. Furthermore in other bone diseases, hyperparathyroidism for instance and especially renal osteodystrophy, bone mineral loss is particularly premature and pronounced in the hand and we therefore decided for the moment to use the hand for the neutron activation analysis of bone calcium. The technique enabled us to measure the calcium concentration of the hand bones in hemodialysed subjects and in patients with primitive osteoporosis

  14. Antiseptic solutions modulate the paracrine-like activity of bone chips: differential impact of chlorhexidine and sodium hypochlorite.

    Science.gov (United States)

    Sawada, Kosaku; Caballé-Serrano, Jordi; Bosshardt, Dieter D; Schaller, Benoit; Miron, Richard J; Buser, Daniel; Gruber, Reinhard

    2015-09-01

    Chemical decontamination increases the availability of bone grafts; however, it remains unclear whether antiseptic processing changes the biological activity of bone. Bone chips were incubated with four different antiseptic solutions including (1) povidone-iodine (0.5%), (2) chlorhexidine diguluconate (0.2%), (3) hydrogen peroxide (1%) and (4) sodium hypochlorite (0.25%). After 10 min. of incubation, changes in the capacity of the bone-conditioned medium (BCM) to modulate gene expression of gingival fibroblasts was investigated. Conditioned medium obtained from freshly prepared bone chips increased the expression of TGF-β target genes interleukin 11 (IL11), proteoglycan4 (PRG4), NADPH oxidase 4 (NOX4), and decreased the expression of adrenomedullin (ADM), and pentraxin 3 (PTX3) in gingival fibroblasts. Incubation of bone chips with 0.2% chlorhexidine, followed by vigorously washing resulted in a BCM with even higher expression of IL11, PRG4 and NOX4. These findings were also detected with a decrease in cell viability and an activation of apoptosis signalling. Chlorhexidine alone, at low concentrations, increased IL11, PRG4 and NOX4 expression, independent of the TGF-β receptor I kinase activity. In contrast, 0.25% sodium hypochlorite almost entirely abolished the activity of BCM, whereas the other two antiseptic solutions, 1% hydrogen peroxide and 0.5% povidone-iodine, had relatively no impact respectively. These in vitro findings demonstrate that incubation of bone chips with chlorhexidine differentially affects the activity of the respective BCM compared to the other antiseptic solutions. The data further suggest that the main effects are caused by chlorhexidine remaining in the BCM after repeated washing of the bone chips. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Repair of giant postlaminectomy pseudomeningocele with fast-resorbing polymer mesh: technical report of 2 cases.

    Science.gov (United States)

    Alvarez, Carlos M; Urakov, Timur M; Vanni, Steven

    2018-03-01

    Pseudomeningocele is a rare but well-known complication of lumbar spine surgery, which arises in 0.068%-0.1% of individuals in large series of patients undergoing laminectomy and in up to 2% of patients with postlaminectomy symptoms. In symptomatic pseudomeningoceles, surgical reexploration and repair of the dural defect are typically necessary. Whereas the goals of pseudomeningocele repair, which are extirpation of the pseudomeningocele cavity and elimination of extradural dead space, can typically be achieved by primary closure performed using nonabsorbable sutures, giant pseudomeningoceles (> 8 cm) can require more elaborate repair in which fibrin glues, dural substitute, myofascial flaps, or all of the above are used. The authors present 2 cases of postsurgical symptomatic giant pseudomeningoceles that were repaired using a fast-resorbing polymer mesh-supported reconstruction technique, which is described here for the first time.

  16. Measurement of trace cadmium and elements in bone by epithermal neutron activation analysis

    International Nuclear Information System (INIS)

    Dowlati, R.; Jervis, R.E.

    1991-01-01

    Epithermal neutron activation analysis (ENAA) was applied to measure quantitatively Cd and other elements in bone samples from control and Cd-fed rats. This method was found to be non-destructive to the bone samples, with no sign of 'radiolytic charring' and was sensitive enough to detect and quantify Cd in bone samples at normal levels for mammals (viz. 0.5-1.0 μg/g) and higher. Two different thermal neutron shield materials were utilized, namely cadmium and boron. The boron shield resulted in a 27% improvement in the detection limit of Cd in bone. The accuracy of ENAA for Cd was assessed by intercomparison with electrothermal atomic absorption spectrophotometry (ETAAS), and the results in fair agreement (±23%) with those from ENAA

  17. Bone and fat connection in aging bone.

    Science.gov (United States)

    Duque, Gustavo

    2008-07-01

    The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

  18. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2015-01-01

    Full Text Available The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better

  19. Structurally-diverse, PPARγ-activating environmental toxicants induce adipogenesis and suppress osteogenesis in bone marrow mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Watt, James; Schlezinger, Jennifer J.

    2015-01-01

    Environmental obesogens are a newly recognized category of endocrine disrupting chemicals that have been implicated in contributing to the rising rates of obesity in the United States. While obesity is typically regarded as an increase in visceral fat, adipocyte accumulation in the bone has been linked to increased fracture risk, lower bone density, and osteoporosis. Exposure to environmental toxicants that activate peroxisome proliferator activated receptor γ (PPARγ), a critical regulator of the balance of differentiation between adipogenesis and osteogenesis, may contribute to the increasing prevalence of osteoporosis. However, induction of adipogenesis and suppression of osteogenesis are separable activities of PPARγ, and ligands may selectively alter these activities. It currently is unknown whether suppression of osteogenesis is a common toxic endpoint of environmental PPARγ ligands. Using a primary mouse bone marrow culture model, we tested the hypothesis that environmental toxicants acting as PPARγ agonists divert the differentiation pathway of bone marrow-derived multipotent mesenchymal stromal cells towards adipogenesis and away from osteogenesis. The toxicants tested included the organotins tributyltin and triphenyltin, a ubiquitous phthalate metabolite (mono-(2-ethylhexyl) phthalate, MEHP), and two brominated flame retardants (tetrabromobisphenol-a, TBBPA, and mono-(2-ethylhexyl) tetrabromophthalate, METBP). All of the compounds activated PPARγ1 and 2. All compounds increased adipogenesis (lipid accumulation, Fabp4 expression) and suppressed osteogenesis (alkaline phosphatase activity, Osx expression) in mouse primary bone marrow cultures, but with different potencies and efficacies. Despite structural dissimilarities, there was a strong negative correlation between efficacies to induce adipogenesis and suppress osteogenesis, with the organotins being distinct in their exceptional ability to suppress osteogenesis. As human exposure to a mixture of

  20. The use of bone scintigraphy to detect active Hansen's disease in mutilated patients

    International Nuclear Information System (INIS)

    Braga, F.J.H.N.; Foss, N.T.; Ferriolli, E.; Pagnano, C.; Miranda, J.R.A.; De Moraes, R.

    1999-01-01

    Mutilation of extremities was very frequent in patients affected by leprosy in the past; although it is now much less common, it is still seen, mainly in patients with long-term disease. In general, mutilation of the nose and ears is caused by the bacillus and mutilation of the hands and feet a consequence of chronic trauma. Leprosy must be chronically treated and any decision to interrupt therapy is based on laboratory tests and biopsy. Scintigraphy is a non-invasive procedure which could be of great value in to determining disease activity. We studied eight patients (five males and three females, aged 64-73 years) who presented with mutilation of the nose (2), ear (1), feet (3) or foot and hand (2). Conventional three-phase bone scintigraphy (750 MBq) and X-ray examinations of the affected areas were performed in all patients. Bone scintigraphy was abnormal in four patients (the presence of bacilli was confirmed by biopsy in two of them), and normal in the other four. In all patients except for the one with ear mutilation, radiography only showed the absence of bone. We conclude that bone scintigraphy is very useful to determine disease activity in cases of mutilation caused by leprosy. It seems to be superior to conventional radiography and may enable bone biopsies to be avoided. (orig.)

  1. PET/CT-guided biopsies of metabolically active bone lesions: applications and clinical impact

    Energy Technology Data Exchange (ETDEWEB)

    Klaeser, Bernd; Wartenberg, Jan; Weitzel, Thilo; Krause, Thomas [Bern University Hospital and University of Bern, Department of Nuclear Medicine, Inselspital, Bern (Switzerland); Wiskirchen, Jakub [Bern University Hospital and University of Bern, Department of Nuclear Medicine, Inselspital, Bern (Switzerland); University Hospital Tuebingen, Department of Radiology, Neuroradiology, and Nuclear Medicine, Tuebingen (Germany); Schmid, Ralph A. [Bern University Hospital and University of Bern, Department of Thoracic Surgery, Inselspital, Bern (Switzerland); Mueller, Michel D. [Bern University Hospital and University of Bern, Department of Obstetrics and Gynaecology, Inselspital, Bern (Switzerland)

    2010-11-15

    In a minority of cases a definite diagnosis and stage grouping in cancer patients is not possible based on the imaging information of PET/CT. We report our experience with percutaneous PET/CT-guided bone biopsies to histologically verify the aetiology of hypermetabolic bone lesions. We retrospectively reviewed the data of 20 consecutive patients who underwent multimodal image-guided bone biopsies using a dedicated PET/CT system in a step-by-step technique. Technical and clinical success rates of PET/CT-guided biopsies were evaluated. Questionnaires were sent to the referring physicians to assess the impact of biopsies on patient management and to check the clinical need for PET/CT-guided biopsies. Clinical indications for biopsy were to histologically verify the aetiology of metabolically active bone lesions without a morphological correlate confirming the suspicion of metastases in 15 patients, to determine the origin of suspected metastases in 3 patients and to evaluate the appropriateness of targeted therapy options in 2 patients. Biopsies were technically successful in all patients. In 19 of 20 patients a definite histological diagnosis was possible. No complications or adverse effects occurred. The result of PET/CT-guided bone biopsies determined a change of the planned treatment in overall 56% of patients, with intramodality changes, e.g. chemotherapy with palliative instead of curative intent, and intermodality changes, e.g. systemic therapy instead of surgery, in 22 and 50%, respectively. PET/CT-guided bone biopsies are a promising alternative to conventional techniques to make metabolically active bone lesions - especially without a distinctive morphological correlate - accessible for histological verification. PET/CT-guided biopsies had a major clinical impact in patients who otherwise cannot be reliably stage grouped at the time of treatment decisions. (orig.)

  2. The mean active bone marrow dose to the adult population of the United States from diagnostic radiology

    International Nuclear Information System (INIS)

    Shleien, B.; Tucker, T.T.; Johnson, D.W.

    1977-01-01

    Estimates, based on an empirical model and computer program, have been calculated and are presented on the mean active bone marrow dose to adults from diagnostic radiography, fluoroscopy, and dental radiography as practiced in the United States in 1970. The annual per capita mean active bone marrow dose in 1970 to adults from the above practices is estimated to be 103 mrad; 77 percent, 20 percent, and 3 percent from radiographic, fluoroscopic and dental examinations respectively. Examinations of the upper and lower abdomen contribute approximately 39 percent each to the total mean active bone marrow dose for adults; those of the pelvis 4 percent; the thorax 12 percent; and head and neck examinations (including dental) contribute about 6 percent. The per capita mean active bone marrow dose for various age groups is discussed. Contributions to the dose within a given age group from different examinations indicate that in the 15-34 year old age group Lumbar and Lumbosacral Spine examinations contribute most to the mean active bone marrow dose. Thereafter Upper G I Series and Barium Enemas are the highest contributors. Comparisons are made with results of the 1964 U.S. X-ray survey and similar surveys from other nations

  3. In Vivo Evaluation of an Injectable Premixed Radiopaque Calcium Phosphate Cement

    Directory of Open Access Journals (Sweden)

    Jonas Åberg

    2011-01-01

    Full Text Available In this work a radiopaque premixed calcium phosphate cement (pCPC has been developed and evaluated in vivo. Radiopacity was obtained by adding 0–40 % zirconia to the cement paste. The effects of zirconia on setting time, strength and radiopacity were evaluated. In the in vivo study a 2 by 3.5 mm cylindrical defect in a rat vertebrae was filled with either the pCPC, PMMA or bone chips. Nano-SPECT CT analysis was used to monitor osteoblast activity during bone regeneration. The study showed that by adding zirconia to the cement the setting time becomes longer and the compressive strength is reduced. All materials evaluated in the in vivo study filled the bone defect and there was a strong osteoblast activity at the injury site. In spite of the osteoblast activity, PMMA blocked bone healing and the bone chips group showed minimal new bone formation. At 12 weeks the pCPC was partially resorbed and replaced by new bone with good bone ingrowth. The radiopaque pCPC may be considered to be used for minimal invasive treatment of vertebral fractures since it has good handling, radiopacity and allows healing of cancellous bone in parallel with the resorption of the cement.

  4. Reconstructive periodontal therapy with simultaneous ridge augmentation. A clinical and histological case series report.

    Science.gov (United States)

    Windisch, Péter; Szendroi-Kiss, Dóra; Horváth, Attila; Suba, Zsuzsanna; Gera, István; Sculean, Anton

    2008-09-01

    Treatment of intrabony periodontal defects with a combination of a natural bone mineral (NBM) and guided tissue regeneration (GTR) has been shown to promote periodontal regeneration in intrabony defects. In certain clinical situations, the teeth presenting intrabony defects are located at close vicinity of the resorbed alveolar ridge. In these particular cases, it is of clinical interest to simultaneously reconstruct both the intrabony periodontal defect and the resorbed alveolar ridge, thus allowing insertion of endosseous dental implants. The aim of the present study was to present the clinical and histological results obtained with a new surgical technique designed to simultaneously reconstruct the intrabony defect and the adjacently located resorbed alveolar ridge. Eight patients with chronic advanced periodontitis displaying intrabony defects located in the close vicinity of resorbed alveolar ridges were consecutively enrolled in the study. After local anesthesia, mucoperiosteal flaps were raised, the granulation tissue removed, and the roots meticulously scaled and planed. A subepithelial connective tissue graft was harvested from the palate and sutured to the oral flap. The intrabony defect and the adjacent alveolar ridge were filled with a NBM and subsequently covered with a bioresorbable collagen membrane (GTR). At 11-20 months (mean, 13.9+/-3.9 months) after surgery, implants were placed, core biopsies retrieved, and histologically evaluated. Mean pocket depth reduction measured 3.8+/-1.7 mm and mean clinical attachment level gain 4.3+/-2.2 mm, respectively. Reentry revealed in all cases a complete fill of the intrabony component and a mean additional vertical hard tissue gain of 1.8+/-1.8 mm. The histologic evaluation indicated that most NBM particles were surrounded by bone. Mean new bone and mean graft area measured 17.8+/-2.8% and 32.1+/-8.3%, respectively. Within their limits, the present findings indicate that the described surgical approach may be

  5. UMF-synthetase activity in rat tissue extracts with the bone 4 marrow form of radiation sickness

    International Nuclear Information System (INIS)

    Levitova, E.N.; Koshcheenko, N.N.; Romantsev, E.F.

    1986-01-01

    Whole-body γ-irradiation of rats with a dose inducing bone marrow radiation syndrome caused phase organospecific chages in UMP-synthase activity. Disturbances of enzymic activity in the bone marrow and spleen well correlated with the dynamics of interphase and reproductive cell death. In brain extracts, UMP biosynthesis from orotic acid did not undergo essential changes

  6. Sr/Ca mass ratio determination in bones using fast neutron activation analysis

    International Nuclear Information System (INIS)

    Hult, Mikael; Fessler, Andreas

    1998-01-01

    The Sr/Ca mass ratio in human bones reveals information regarding the diet which is of interest in archaeology. By using fast neutron activation analysis this ratio can be measured in a non-destructive manner, which is important when bones are considered too precious to allow for destructive analysis. Simulations and measurements showed that the nuclear reactions 88 Sr(n, 2n) 87m Sr and 44 Ca(n, p) 44 K are highly useful for the purpose

  7. The intensity of physical activity influences bone mineral accrual in childhood: the childhood health, activity and motor performance school (the CHAMPS) study, Denmark.

    Science.gov (United States)

    Heidemann, Malene; Mølgaard, Christian; Husby, Steffen; Schou, Anders J; Klakk, Heidi; Møller, Niels Chr; Holst, René; Wedderkopp, Niels

    2013-03-02

    Studies indicate genetic and lifestyle factors can contribute to optimal bone development. In particular, the intensity level of physical activity may have an impact on bone health. This study aims to assess the relationship between physical activity at different intensities and Bone Mineral Content (BMC), Bone Mineral Density (BMD) and Bone Area (BA) accretion. This longitudinal study is a part of The CHAMPS study-DK. Whole-body DXA scans were performed at baseline and after two years follows up. BMC, BMD, and BA were measured. The total body less head (TBLH) values were used. Physical activity (PA) was recorded by accelerometers (ActiGraph, model GT3X). Percentages of different PA intensity levels were calculated and log odds of two intensity levels of activity relative to the third level were calculated. Multilevel regression analyses were used to assess the relationship between the categories of physical activity and bone traits. Of 800 invited children, 742 (93%) accepted to participate. Of these, 682/742 (92%) participated at follow up. Complete datasets were obtained in 602/742 (81%) children. Mean (range) of age was 11.5 years (9.7-13.9). PA at different intensity levels was for boys and girls respectively, sedentary 62% and 64%, low 29% for both genders and moderate to high 9% and 7% of the total time. Mean (range) BMC, BMD, and BA was 1179 g (563-2326), 0.84 g/cm2 (0.64-1.15) and 1393 cm2 (851-2164), respectively. Valid accelerometer data were obtained for a mean of 6.1 days, 13 hours per day. There 7was a positive relationship between the log odds of moderate to high-level PA versus low level activity and BMC, BMD and BA. Children with an increased proportion of time in moderate to high-level activity as opposed to sedentary and low-level activity achieved positive effects on BMC, BMD and BA.

  8. 3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep.

    Science.gov (United States)

    Ding, Ming; Henriksen, Susan S; Martinetti, Roberta; Overgaard, Søren

    2017-11-01

    Early fixation of total joint arthroplasties is crucial for ensuring implant survival. An alternative bone graft material in revision surgery is needed to replace the current gold standard, allograft, seeing that the latter is associated with several disadvantages. The incubation of such a construct in a perfusion bioreactor has been shown to produce viable bone graft materials. This study aimed at producing larger amounts of viable bone graft material (hydroxyapatite 70% and β-tricalcium-phosphate 30%) in a novel perfusion bioreactor. The abilities of the bioreactor-activated graft material to induce early implant fixation were tested in a bilateral implant defect model in sheep, with allograft as the control group. Defects were bilaterally created in the distal femurs of the animals, and titanium implants were inserted. The concentric gaps around the implants were randomly filled with either allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while no significant differences between groups were found regarding early implant fixation. The microarchitecture of the bone formed by the synthetic graft materials resembled that of allograft. Histomorphometry revealed that allograft induced significantly more bone and less fibrous tissue (p formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2465-2476, 2017. © 2016 Wiley Periodicals, Inc.

  9. Bone response to hydroxyapatites with open porosity of animal origin (porcine [OsteoBiol mp3] and bovine [Endobon]): a radiological and histomorphometric study.

    Science.gov (United States)

    Ramírez-Fernández, MaPiedad; Calvo-Guirado, Jose Luis; Delgado-Ruiz, Rafael Arcesio; Maté-Sánchez Del Val, José Eduardo; Vicente-Ortega, Vicente; Meseguer-Olmos, Luis

    2011-07-01

    To carry out a radiological and histomorphometric evaluation of bone response to two xenografts of animal origin, one porcine, and the other bovine, inserted in rabbits' tibiae. Twenty New Zealand rabbits weighing 3900-4500 g were used. Twenty bovine bone grafts (Endobon) in granulated form of 500-1000 μm granulometry were inserted in the proximal metaphyseal area of the animals' right tibia, and 20 porcine bone grafts (OsteoBiol mp3) in granulated form of 600-1000 μm granulometry were inserted in the proximal metaphyseal area of the animals' left tibia. Following graft insertion, the animals were sacrificed in four groups of five, after 1, 2, 3 and 4 months, respectively. Anteroposterior and lateral radiographs were taken. Samples were processed for observation under light microscopy. Histomorphometric measurements were presented as mean values ± standard deviations. At 4 months after treatment, the bone defects displayed radiological images that showed complete repair of osseous defects. Histomorphometric evaluation showed that for the porcine xenograft, the study averages for newly formed bone represented 22.8 ± 1.8%, for residual graft material 23.6 ± 3% and for connective tissue 53.5 ± 2.5%, while for the bovine xenograft newly formed bone represented 23.1 ± 1.8%, residual graft material 39.4 ± 3% and non-mineralized connective tissue 37.5 ± 2.5%. The biomaterials assessed in the study were shown to be biocompatible and osteoconductive. Collagenized porcine xenografts proved more resorbable than bovine xenografts. Both can be used as possible bone substitutes without interfering with normal reparative bone processes. © 2011 John Wiley & Sons A/S.

  10. The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness.

    Science.gov (United States)

    Makowski, Alexander J; Uppuganti, Sasidhar; Wadeer, Sandra A; Whitehead, Jack M; Rowland, Barbara J; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S

    2014-05-01

    Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of these important factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4-/- littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4-/- mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective of age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4-/- mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also in maintaining bone toughness and fracture toughness. Published by Elsevier Inc.

  11. The Loss of Activating Transcription Factor 4 (ATF4) Reduces Bone Toughness and Fracture Toughness

    Science.gov (United States)

    Makowski, Alexander J.; Uppuganti, Sasidhar; Waader, Sandra A.; Whitehead, Jack M.; Rowland, Barbara J.; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S.

    2014-01-01

    Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of the seimportant factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4−/− littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4−/− mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4−/− mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1 Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also maintaining bone toughness and fracture toughness. PMID:24509412

  12. In vitro determination of inorganic constituents in bone tissues using neutron activation analysis

    International Nuclear Information System (INIS)

    Takata, Marcelo Kazuo

    2003-01-01

    In the past years, there has been an increasing interest in bone analyses since they are deposits of essential and toxic elements. Besides they have supporting function of human body and protect vital organs. Besides, analyses of inorganic constituents in bones have been carried out to study bone diseases such as osteoporosis and tumors in bones. In this work, an adequate experimental procedure was established for bone tissue treatment, and instrumental neutron activation analysis was applied to trace element determinations in freeze-dried cortical and trabecular tissues and whole bone ash from animal (porcine and bovine) and human ribs. Using short and long-period irradiations at the IEA-R1 nuclear research reactor, the elements Ba, Br, Ca, Cl, Fe, K, Mg, Mn, Na, P, Rb, Sb, Sr and Zn were determined in bone tissues. To validate the analytical methodology, biological certified reference materials were analyzed and their results showed good precision and accuracy. Besides analyses of a bovine rib bone presented precise data for most elements with relative standard deviations lower than 14 %. This result demonstrated that the procedure defined for bone tissue treatment was appropriate to obtain homogeneous samples. However, the calcination was not suitable for whole bone treatment due to loss of Br and Cl. Statistical t test was applied to compare the results obtained for different tissues of bone and also the results found for ribs of two animal species. Comparisons between the results obtained for correspondent tissues of porcine and bovine ribs present different element concentration. Moreover, cortical and trabecular tissues of humans presented different concentrations for all the elements analyzed in this work. These findings indicate that trace elements in bone samples have to be separately studied. (author)

  13. Bone markers in craniofacial bone deformations and dysplasias

    Directory of Open Access Journals (Sweden)

    Monika Seifert

    2015-10-01

    Full Text Available Various forms of bony deformations and dysplasias are often present in the facial skeleton. Bone defects can be either localized or general. Quite often they are not only present in the skull but also can be found in other parts of the skeleton. In many cases the presence and levels of specific bone markers should be measured in order to fully describe their activity and presence in the skeleton. Fibrous dysplasia (FD is the most common one in the facial skeleton; however, other bone deformations regarding bone growth and activity can also be present. Every clinician should be aware of all common, rare and uncommon bony diseases and conditions such as cherubism, Paget’s disease, osteogenesis imperfecta and others related to genetic conditions. We present standard (calcium, parathyroid hormone, calcitonin, alkaline phosphatase, vitamin D and specialized bone markers (pyridinium, deoxypyridinium, hydroxyproline, RANKL/RANK/OPG pathway, growth hormone, insulin-like growth hormone-1 that can be used to evaluate, measure or describe the processes occurring in craniofacial bones.

  14. Radiographic and histological study of perennial bone defect repair in rat calvaria after treatment with blocks of porous bovine organic graft material.

    Science.gov (United States)

    Marins, Lucele Vieira; Cestari, Tania Mary; Sottovia, André Dotto; Granjeiro, José Mauro; Taga, Rumio

    2004-03-01

    Over the last few years, various bone graft materials of bovine origin to be used in oromaxillofacial surgeries have entered the market. In the present study, we determined the capacity of a block organic bone graft material (Gen-ox, Baumer SA, Brazil) prepared from bovine cancellous bone to promote the repair of critical size bone injuries in rat calvaria. A transosseous defect measuring approximately 8mm in diameter was performed with a surgical trephine in the parietal bone of 25 rats. In 15 animals, the defects were filled with a block of graft material measuring 8mm in diameter and soaked in the animal's own blood, and in the other 10 animals the defects were only filled with blood clots. The calvariae of rats receiving the material were collected 1, 3 and 6 months after surgery, and those of animals receiving the blood clots were collected immediately and 6 months after surgery. During surgery, the graft material was found to be of easy handling and to adapt perfectly to the receptor bed after soaking in blood. The results showed that, in most animals treated, the material was slowly resorbed and served as a space filling and maintenance material, favoring angiogenesis, cell migration and adhesion, and bone neoformation from the borders of the lesion. However, a foreign body-type granulomatous reaction, with the presence of numerous giant cells preventing local bone neoformation, was observed in two animals of the 1-month subgroup and in one animal of the 3-month subgroup. These cases were interpreted as resulting from the absence of demineralization and the lack of removal of potential antigen factors during production of the biomaterial. We conclude that, with improvement in the quality control of the material production, block organic bone matrix will become a good alternative for bone defect repair in the oromaxillofacial region due to its high osteoconductive capacity.

  15. Mice with cancer-induced bone pain show a marked decline in day/night activity.

    Science.gov (United States)

    Majuta, Lisa A; Guedon, Jean-Marc G; Mitchell, Stefanie A T; Kuskowski, Michael A; Mantyh, Patrick W

    2017-09-01

    Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status.

  16. * Three-Dimensional Bioprinting of Polycaprolactone Reinforced Gene Activated Bioinks for Bone Tissue Engineering.

    Science.gov (United States)

    Cunniffe, Gráinne M; Gonzalez-Fernandez, Tomas; Daly, Andrew; Sathy, Binulal N; Jeon, Oju; Alsberg, Eben; Kelly, Daniel J

    2017-09-01

    Regeneration of complex bone defects remains a significant clinical challenge. Multi-tool biofabrication has permitted the combination of various biomaterials to create multifaceted composites with tailorable mechanical properties and spatially controlled biological function. In this study we sought to use bioprinting to engineer nonviral gene activated constructs reinforced by polymeric micro-filaments. A gene activated bioink was developed using RGD-γ-irradiated alginate and nano-hydroxyapatite (nHA) complexed to plasmid DNA (pDNA). This ink was combined with bone marrow-derived mesenchymal stem cells (MSCs) and then co-printed with a polycaprolactone supporting mesh to provide mechanical stability to the construct. Reporter genes were first used to demonstrate successful cell transfection using this system, with sustained expression of the transgene detected over 14 days postbioprinting. Delivery of a combination of therapeutic genes encoding for bone morphogenic protein and transforming growth factor promoted robust osteogenesis of encapsulated MSCs in vitro, with enhanced levels of matrix deposition and mineralization observed following the incorporation of therapeutic pDNA. Gene activated MSC-laden constructs were then implanted subcutaneously, directly postfabrication, and were found to support superior levels of vascularization and mineralization compared to cell-free controls. These results validate the use of a gene activated bioink to impart biological functionality to three-dimensional bioprinted constructs.

  17. A mechano-regulatory bone-healing model incorporating cell-phenotype specific activity

    NARCIS (Netherlands)

    Isaksson, H.E.; Donkelaar, van C.C.; Huiskes, R.; Ito, K.

    2008-01-01

    Phenomenological computational models of tissue regeneration and bone healing have been only partially successful in predicting experimental observations. This may be a result of simplistic modeling of cellular activity. Furthermore, phenomenological models are limited when considering the effects

  18. Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation.

    Science.gov (United States)

    McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

    2015-07-01

    Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. © 2015. Published by The Company of Biologists Ltd.

  19. Posterior lumbar interbody fusion using nonresorbable poly-ether-ether-ketone versus resorbable poly-L-lactide-co-D,L-lactide fusion devices: a prospective, randomized study to assess fusion and clinical outcome

    NARCIS (Netherlands)

    Jiya, T.U.; Smit, T.H.; Deddens, J.; Mullender, M.G.

    2009-01-01

    STUDY DESIGN: A prospective randomized clinical study. OBJECTIVE.: To assess fusion, clinical outcome, and complications. SUMMARY OF BACKGROUND DATA: Resorbable poly-L- lactide-co-D,L-lactide (PLDLLA) cages intended to aid spinal interbody fusion have been introduced into clinical practice within

  20. Synergistic effects of tributyltin and 2,3,7,8-tetrachlorodibenzo-p-dioxin on differentiating osteoblasts and osteoclasts

    International Nuclear Information System (INIS)

    Koskela, Antti; Viluksela, Matti; Keinänen, Meeri; Tuukkanen, Juha; Korkalainen, Merja

    2012-01-01

    The purpose of this study was to examine the effects of the persistent and accumulative environmental pollutants tributyltin (TBT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) individually and in combination on differentiating bone cells. TBT and TCDD are chemically distinct compounds with different mechanisms of toxicity, but they typically have the same sources of exposure and both have been shown to affect bone development at low exposure levels. Bone marrow stem cells were isolated from femurs and tibias of C57BL/6 J mice, differentiated in culture into osteoblasts or osteoclasts and exposed to 0.1–10 nM TBT, 0.01–1 nM TCDD or 10 nM TBT + 1 nM TCDD. In osteoblasts, the combined exposure to TBT and TCDD significantly decreased the mRNA expression of alkaline phosphatase and osteocalcin more than TBT or TCDD alone. PCR array showed different gene expression profiles for TBT and TCDD individually, and the combination evoked several additional alterations in gene expression. Expression of aryl hydrocarbon receptor repressor (AHRR) was increased by TCDD as expected, but simultaneous exposure to TBT prevented the increase thus potentially strengthening AHR-mediated effects of TCDD. The number of osteoclasts was reduced by TCDD alone and in combination with TBT, but TBT alone had no effect. However, the total area of resorbed bone was remarkably lower after combined exposure than after TBT or TCDD alone. In conclusion, very low concentrations of TBT and TCDD have synergistic deleterious effects on bone formation and additive effects on bone resorption. -- Highlights: ► Combined exposure to TCDD and TBT evoked a unique gene expression profile. ► Osteoblast differentiation was synergistically disturbed after combined exposure. ► Bone resorbing activity was additively decreased after combined exposure.

  1. Synergistic effects of tributyltin and 2,3,7,8-tetrachlorodibenzo-p-dioxin on differentiating osteoblasts and osteoclasts

    Energy Technology Data Exchange (ETDEWEB)

    Koskela, Antti, E-mail: antti.koskela@oulu.fi [University of Oulu, Department of Anatomy and Cell Biology, Oulu (Finland); Viluksela, Matti [National Institute for Health and Welfare, Department of Environmental Health, Kuopio (Finland); Keinänen, Meeri; Tuukkanen, Juha [University of Oulu, Department of Anatomy and Cell Biology, Oulu (Finland); Korkalainen, Merja [National Institute for Health and Welfare, Department of Environmental Health, Kuopio (Finland)

    2012-09-01

    The purpose of this study was to examine the effects of the persistent and accumulative environmental pollutants tributyltin (TBT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) individually and in combination on differentiating bone cells. TBT and TCDD are chemically distinct compounds with different mechanisms of toxicity, but they typically have the same sources of exposure and both have been shown to affect bone development at low exposure levels. Bone marrow stem cells were isolated from femurs and tibias of C57BL/6 J mice, differentiated in culture into osteoblasts or osteoclasts and exposed to 0.1–10 nM TBT, 0.01–1 nM TCDD or 10 nM TBT + 1 nM TCDD. In osteoblasts, the combined exposure to TBT and TCDD significantly decreased the mRNA expression of alkaline phosphatase and osteocalcin more than TBT or TCDD alone. PCR array showed different gene expression profiles for TBT and TCDD individually, and the combination evoked several additional alterations in gene expression. Expression of aryl hydrocarbon receptor repressor (AHRR) was increased by TCDD as expected, but simultaneous exposure to TBT prevented the increase thus potentially strengthening AHR-mediated effects of TCDD. The number of osteoclasts was reduced by TCDD alone and in combination with TBT, but TBT alone had no effect. However, the total area of resorbed bone was remarkably lower after combined exposure than after TBT or TCDD alone. In conclusion, very low concentrations of TBT and TCDD have synergistic deleterious effects on bone formation and additive effects on bone resorption. -- Highlights: ► Combined exposure to TCDD and TBT evoked a unique gene expression profile. ► Osteoblast differentiation was synergistically disturbed after combined exposure. ► Bone resorbing activity was additively decreased after combined exposure.

  2. Effects of active acromegaly on bone mRNA and microRNA expression patterns.

    Science.gov (United States)

    Belaya, Zhanna; Grebennikova, Tatiana; Melnichenko, Galina; Nikitin, Alexey; Solodovnikov, Alexander; Brovkina, Olga; Grigoriev, Andrey; Rozhinskaya, Liudmila; Lutsenko, Alexander; Dedov, Ivan

    2018-04-01

    To evaluate the response of bone to chronic long-term growth hormone (GH) and insulin-like growth factor-1 (IGF1) excess by measuring the expression of selected mRNA and microRNA (miR) in bone tissue samples of patients with active acromegaly. Case-control study. Bone tissue samples were obtained during transsphenoidal adenomectomy from the sphenoid bone (sella turcica) from 14 patients with clinically and biochemically confirmed acromegaly and 10 patients with clinically non-functioning pituitary adenoma (NFPA) matched by sex and age. Expression of genes involved in the regulation of bone remodeling was studied using quantitative polymerase chain reaction (qPCR). Of the genes involved in osteoblast and osteoclast activity, only alkaline phosphatase (ALP) mRNA was 50% downregulated in patients with acromegaly. GH excess caused increased expression of the Wnt signaling antagonists ( DKK1) and agonists ( WNT10B) and changes in the levels of miR involved in mesenchymal stem cell commitment to chondrocytes (miR-199a-5p) or adipocytes (miR-27-5p, miR-125b-5p, miR-34a-5p, miR-188-3p) P  Acromegaly had minimal effects on tested mRNAs specific to osteoblast or osteoclast function except for downregulated ALP expression. The expressions of miR known to be involved in mesenchymal stem cell commitment and downregulated TWIST1 expression suggest acromegaly has a negative effect on osteoblastogenesis. © 2018 European Society of Endocrinology.

  3. Alveolar wound healing after implantation with a pool of commercially available bovine bone morphogenetic proteins (BMPs): a histometric study in rats.

    Science.gov (United States)

    Calixto, Romeu Felipe Elias; Teófilo, Juliana Mazzonetto; Brentegani, Luiz Guilherme; Lamano-Carvalho, Teresa Lúcia

    2007-01-01

    The capacity of a commercially available pool of bovine bone morphogenetic proteins (BMPs) to stimulate osteogenesis in the rat alveolar healing was investigated by histometric analysis. Male rats were anesthetized and had their upper incisor extracted. A pool of purified bovine BMPs adsorbed to microgranular resorbable hydroxyapatite was agglutinated with bovine collagen and saline before implantation into the alveolar socket. The implanted and control rats (n=30 per group) were sacrificed 1 to 9 weeks postoperatively, the hemi-maxillae were decalcified, processed for paraffin embedding and semi-serial longitudinal sections were obtained and stained with hematoxylin and eosin. The volume fraction of alveolar healing components was estimated by a differential point-counting method in histologic images. The results showed that in both, control and implanted rats, the alveolar healing followed the histologic pattern usually described in the literature. Quantitative data confirmed that the BMPs mixture did not stimulate new bone formation in the alveolar socket of implanted rats. These results suggest that the pool of BMPs adsorbed to hydroxyapatite and agglutinated with bovine collagen did not warrant incorporation of the osteoinductive proteins to a slow-absorption system that would allow a BMPs release rate compatible to that of new bone formation, and thus more adequate to osteoinduction.

  4. Activation of Src kinase by protein-tyrosine phosphatase-PEST in osteoclasts: comparative analysis of the effects of bisphosphonate and protein-tyrosine phosphatase inhibitor on Src activation in vitro.

    Science.gov (United States)

    Chellaiah, Meenakshi A; Schaller, Michael D

    2009-08-01

    PTP-PEST is involved in the regulation of sealing ring formation in osteoclasts. In this article, we have shown a regulatory role for PTP-PEST on dephosphorylation of c-Src at Y527 and phosphorylation at Y418 in the catalytic site. Activation of Src in osteoclasts by over-expression of PTP-PEST resulted in the phosphorylation of cortactin at Y421 and WASP at Y294. Also enhanced as a result, is the interaction of Src, cortactin, and Arp2 with WASP. Moreover, the number of osteoclasts displaying sealing ring and bone resorbing activity was increased in response to PTP-PEST over-expression as compared with control osteoclasts. Cells expressing constitutively active-Src (527YDeltaF) simulate the effects mediated by PTP-PEST. Treatment of osteoclasts with a bisphosphonate alendronate or a potent PTP inhibitor PAO decreased the activity and phosphorylation of Src at Y418 due to reduced dephosphorylation state at Y527. Therefore, Src-mediated phosphorylation of cortactin and WASP as well as the formation of WASP.cortactin.Arp2 complex and sealing ring were reduced in these osteoclasts. Similar effects were observed in osteoclasts treated with an Src inhibitor PP2. We have shown that bisphosphonates could modulate the function of osteoclasts by inhibiting downstream signaling mediated by PTP-PEST/Src, in addition to its effect on the inhibition of the post-translational modification of small GTP-binding proteins such as Rab, Rho, and Rac as shown by others. The promising effects of the inhibitors PP2 and PAO on osteoclast function suggest a therapeutic approach for patients with bone metastases and osteoporosis as an alternative to bisphosphonates.

  5. Differentiation of bone marrow cells with irradiated bone in vitro

    International Nuclear Information System (INIS)

    Toshiyuki Tominaga; Moritoshi Itoman; Izumi, T.; Wakita, R.; Uchino, M.

    1999-01-01

    Disease transmission or infection is an important issue in bone allograft, and irradiation is used for sterilization of graft bones. One of the advantages of bone allograft over biomaterials is that graft bones have osteoinductive factors such as growth factors. Irradiation is reported to decrease the osteoinductive activity in vivo. We investigated the osteoinductive activity of irradiated bone by alkaline phosphatase (ALP) activity in rat bone marrow cell culture. Bones (tibias and femurs of 12-week-old Wistar rats) were cleaned of adhering soft tissue, and the marrow was removed by washing. The bones were defatted, lyophilized, and cut into uniform 70 mg fragments. Then the Bone fragments were irradiated at either 10, 20, 25, 30, 40, or 50 kGy at JAERI. Bone marrow cells were isolated from tibias and femurs of 4-week-old Wistar rats. Cells were plated in tissue culture flask. When primary cultures reached confluence, cells were passaged (4 x 103 cell / cm2) to 6 wells plates. The culture medium consisted of minimum essential medium, 10% fetal bovine serum, ascorbic acid, and antibiotics. At confluence, a cell culture insert was set in the well, and an irradiated bone fragment was placed in it. Then, medium was supplemented with 10 mM ?-glycerophosphate and 1 x 10-8 M dexamethasone. Culture wells were stained by naphthol AS-MX phosphate, N,N-dimethyl formamide, Red violet LB salt on day 0, 7, 14. The density of ALP staining was analyzed by a personal computer. Without bones, ALP staining increased by 50% on day 7 and by 100% on day 14, compared with that on day 0. The other side, with bones irradiated at 30 kGy or lower, ALP staining increased by 150% on day 7, and by 180% on day 14, compared with that on day 0. In the groups of irradiated bones of 40 kGy or higher, the increase in ALP staining was less prominent compared with the groups of irradiated bones of 30 kGy or lower. In the groups of 0-30 kGy irradiation, ALP staining increased in the early period

  6. The influence of dairy consumption and physical activity on ultrasound bone measurements in Flemish children.

    Science.gov (United States)

    De Smet, Stephanie; Michels, Nathalie; Polfliet, Carolien; D'Haese, Sara; Roggen, Inge; De Henauw, Stefaan; Sioen, Isabelle

    2015-03-01

    The study's aim was to analyse whether children's bone status, assessed by calcaneal ultrasound measurements, is influenced by dairy consumption and objectively measured physical activity (PA). Moreover, the interaction between dairy consumption and PA on bone mass was studied. Participants of this cross-sectional study were 306 Flemish children (6-12 years). Body composition was measured with air displacement plethysmography (BodPod), dairy consumption with a Food Frequency Questionnaire, PA with an accelerometer (only in 234 of the 306 children) and bone mass with quantitative ultrasound, quantifying speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness Index (SI). Regression analyses were used to study the associations between dairy consumption, PA, SOS, BUA and SI. Total dairy consumption and non-cheese dairy consumption were positively associated with SOS and SI, but no significant association could be demonstrated with BUA. In contrast, milk consumption, disregarding other dairy products, had no significant effect on calcaneal bone measurements. PA [vigorous PA, moderate to vigorous physical activity (MVPA) and counts per minute] was positively associated and sedentary time was negatively associated with BUA and SI, but no significant influence on SOS could be detected. Dairy consumption and PA (sedentary time and MVPA) did not show any interaction influencing bone measurements. In conclusion, even at young age, PA and dairy consumption positively influence bone mass. Promoting PA and dairy consumption in young children may, therefore, maximize peak bone mass, an important protective factor against osteoporosis later in life.

  7. Evaluation of Posterolateral Lumbar Fusion in Sheep Using Mineral Scaffolds Seeded with Cultured Bone Marrow Cells

    Directory of Open Access Journals (Sweden)

    María D. Cuenca-López

    2014-12-01

    Full Text Available The objective of this study is to investigate the efficacy of hybrid constructs in comparison to bone grafts (autograft and allograft for posterolateral lumbar fusion (PLF in sheep, instrumented with transpedicular screws and bars. Hybrid constructs using cultured bone marrow (BM mesenchymal stem cells (MSCs have shown promising results in several bone healing models. In particular, hybrid constructs made by calcium phosphate-enriched cells have had similar fusion rates to bone autografts in posterolateral lumbar fusion in sheep. In our study, four experimental spinal fusions in two animal groups were compared in sheep: autograft and allograft (reference group, hydroxyapatite scaffold, and hydroxyapatite scaffold seeded with cultured and osteoinduced bone marrow MSCs (hybrid construct. During the last three days of culture, dexamethasone (dex and beta-glycerophosphate (β-GP were added to potentiate osteoinduction. The two experimental situations of each group were tested in the same spinal segment (L4–L5. Spinal fusion and bone formation were studied by clinical observation, X-ray, computed tomography (CT, histology, and histomorphometry. Lumbar fusion rates assessed by CT scan and histology were higher for autograft and allograft (70% than for mineral scaffold alone (22% and hybrid constructs (35%. The quantity of new bone formation was also higher for the reference group, quite similar in both (autograft and allograft. Although the hybrid scaffold group had a better fusion rate than the non-hybrid scaffold group, the histological analysis revealed no significant differences between them in terms of quantity of bone formation. The histology results suggested that mineral scaffolds were partly resorbed in an early phase, and included in callus tissues. Far from the callus area the hydroxyapatite alone did not generate bone around it, but the hybrid scaffold did. In nude mice, labeled cells were induced to differentiate in vivo and monitored

  8. Osseointegration of dental implants in 3D-printed synthetic onlay grafts customized according to bone metabolic activity in recipient site.

    Science.gov (United States)

    Tamimi, Faleh; Torres, Jesus; Al-Abedalla, Khadijeh; Lopez-Cabarcos, Enrique; Alkhraisat, Mohammad H; Bassett, David C; Gbureck, Uwe; Barralet, Jake E

    2014-07-01

    Onlay grafts made of monolithic microporous monetite bioresorbable bioceramics have the capacity to conduct bone augmentation. However, there is heterogeneity in the graft behaviour in vivo that seems to correlate with the host anatomy. In this study, we sought to investigate the metabolic activity of the regenerated bone in monolithic monetite onlays by using positron emission tomography-computed tomography (PET-CT) in rats. This information was used to optimize the design of monetite onlays with different macroporous architecture that were then fabricated using a 3D-printing technique. In vivo, bone augmentation was attempted with these customized onlays in rabbits. PET-CT findings demonstrated that bone metabolism in the calvarial bone showed higher activity in the inferior and lateral areas of the onlays. Histological observations revealed higher bone volume (up to 47%), less heterogeneity and more implant osseointegration (up to 38%) in the augmented bone with the customized monetite onlays. Our results demonstrated for the first time that it is possible to achieve osseointegration of dental implants in bone augmented with 3D-printed synthetic onlays. It was also observed that designing the macropore geometry according to the bone metabolic activity was a key parameter in increasing the volume of bone augmented within monetite onlays. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yuehua, E-mail: yuesjtu@126.com; Zheng, Xinfeng, E-mail: zxf272@126.com; Li, Bo, E-mail: libo@126.com; Jiang, Shengdan, E-mail: jiangsd@126.com; Jiang, Leisheng, E-mail: leisheng_jiang@126.com

    2014-08-15

    Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.

  10. Resistance training and hormone replacement increase MMP-2 activity, quality and quantity of bone in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Markus V.C Souza

    2017-12-01

    Full Text Available Abstract AIMS The aim of the present study was to investigate the influence of resistance training (RT and hormone replacement (HR on MMP-2 activity, biomechanical and physical properties bone of ovariectomized (OVX rats. METHODS Sprague-Dawley female rats were grouped into six experimental groups (n = 11 per group: sham-operated sedentary (SHAM Sed, ovariectomized sedentary (OVX Sed, sham-operated resistance training (SHAM RT, ovariectomized resistance training (OVX RT, ovariectomized sedentary hormone replacement (OVX Sed-HR, and ovariectomized resistance training hormone replacement (OVX RT-HR. HR groups received implanted silastic capsules with a 5% solution of 17β-estradiol (50 mg 17β-estradiol/ml of sunflower oil. In a 12-week RT period (27 sessions; 4-9 climbs the animals climbed a 1.1 m vertical ladder with weights attached to their tails. Biomechanical and physical bone analyses were performed using a universal testing machine, and MMP-2 activity analysis was done by zymography. RESULTS Bone density and bone mineral content was higher in the RT and HR groups. The MMP-2 activity was higher in the RT and HR groups. The biomechanical analysis (stiffness, fracture load and maximum load demonstrated better bone tissue quality in the RT associated with HR. CONCLUSION The RT alone as well as when it is associated with HR was efficient in increasing MMP-2 activity, biomechanical and biophysical properties bone of ovariectomized rats.

  11. Lifetime physical activity and calcium intake related to bone density in young women.

    Science.gov (United States)

    Wallace, Lorraine Silver; Ballard, Joyce E

    2002-05-01

    Osteoporosis is a significant public health problem associated with increased mortality and morbidity. Our aim in this cross-sectional study was to investigate the relationship between lifetime physical activity and calcium intake and bone mineral density (BMD) and BMC (bone mineral content) in 42 regularly menstruating Caucasian women (age 21.26+/-1.91 years, BMI 23.83+/-5.85). BMD and BMC at the lumbar spine (L2-L4), hip (femoral neck, trochanter, total), and total body were assessed by dual energy x-ray absorptiometry (DXA). Lifetime history of physical activity and calcium intake was obtained by a structured interview using valid and reliable instruments. Measures of both lifetime physical activity and calcium intake were highly correlated. In stepwise multiple regression analyses, lean mass was the most important and consistent factor for predicting BMD and BMC at all skeletal sites (attributable r2 = 28.8%-78.7%). Lifetime physical activity contributed to 3.0% of the variation in total body BMD, and life-time weight-bearing physical activity explained 15.1% of variance in lumbar spine BMC. Current calcium intake predicted 6% of the variance in BMD at the femoral neck and trochanter. We found lean mass to be a powerful predictor of BMD and BMC in young women. Because lean mass can be modified to some extent by physical activity, public health efforts must be directed at increasing physical activity throughout the lifespan. Furthermore, our results suggest that adequate calcium intake may help to enhance bone mass, thus decreasing the risk of osteoporotic fracture later in life.

  12. Organotins Are Potent Activators of PPARγ and Adipocyte Differentiation in Bone Marrow Multipotent Mesenchymal Stromal Cells

    Science.gov (United States)

    Yanik, Susan C.; Baker, Amelia H.; Mann, Koren K.; Schlezinger, Jennifer J.

    2011-01-01

    Adipocyte differentiation in bone marrow is potentially deleterious to both bone integrity and lymphopoiesis. Here, we examine the hypothesis that organotins, common environmental contaminants that are dual ligands for peroxisome proliferator–activated receptor (PPAR) γ and its heterodimerization partner retinoid X receptor (RXR), are potent activators of bone marrow adipogenesis. A C57Bl/6-derived bone marrow multipotent mesenchymal stromal cell (MSC) line, BMS2, was treated with rosiglitazone, a PPARγ agonist, bexarotene, an RXR agonist, or a series of organotins. Rosiglitazone and bexarotene potently activated adipocyte differentiation; however, bexarotene had a maximal efficacy of only 20% of that induced by rosiglitazone. Organotins (tributyltin [TBT], triphenyltin, and dibutyltin) also stimulated adipocyte differentiation (EC50 of 10–20nM) but with submaximal, structure-dependent efficacy. In coexposures, both bexarotene and TBT enhanced rosiglitazone-induced adipogenesis. To investigate the contribution of PPARγ to TBT-induced adipogenesis, we examined expression of PPARγ2, as well as its transcriptional target FABP4. TBT-induced PPARγ2 and FABP4 protein expression with an efficacy intermediate between rosiglitazone and bexarotene, similar to lipid accumulation. A PPARγ antagonist and PPARγ-specific small hairpin RNA suppressed TBT-induced differentiation, although to a lesser extent than rosiglitazone-induced differentiation, suggesting that TBT may engage alternate pathways. TBT and bexarotene, but not rosiglitazone, also induced the expression of TGM2 (an RXR target) and ABCA1 (a liver X receptor target). The results show that an environmental contaminant, acting with the same potency as a therapeutic drug, induces PPARγ-dependent adipocyte differentiation in bone marrow MSCs. Activation of multiple nuclear receptor pathways by organotins may have significant implications for bone physiology. PMID:21622945

  13. Fisetin Inhibits Osteoclast Differentiation via Downregulation of p38 and c-Fos-NFATc1 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Sik-Won Choi

    2012-01-01

    Full Text Available The prevention or therapeutic treatment of loss of bone mass is an important means of improving the quality of life for patients with disorders related to osteoclast-mediated bone loss. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Continus coggygria, exhibits various biological activities, but its effect on osteoclast differentiation is unknown. In this study, fisetin dose-dependently inhibited the RANKL-induced osteoclast differentiation with downregulation of the activity or expression of p38, c-Fos, and NFATc1 signaling molecules. The p38/c-Fos/NFATc1-regulated expression of genes required for cell fusion and bone resorption, such as DC-STAMP and cathepsin K, was also inhibited by fisetin. Considering the rescue of fisetin's inhibitory action by NFATc1 over-expression, the cascade of p38-c-Fos-NFATc1 could be strongly involved in the inhibitory effect of fisetin on osteoclast differentiation. Furthermore, fisetin inhibited the bone-resorbing activity of mature osteoclasts. In conclusion, fisetin may be of use in the treatment of osteoclast-related disorders, including osteoporosis.

  14. Unprotected autogenous bone block grafts in anterior maxilla: Resorption rates and clinical outcomes

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    Kosanić Ivan

    2017-01-01

    Full Text Available Background/Aim. The use of autogenous bone grafts for augmentation of the resorbed alveolar ridge is still considered the gold standard in implant dentistry. The aim of this study was to analyze the resorption rate of autogenous bone block grafts from the retromolar region placed in the frontal segment of the upper jaw unprotected by barrier membranes, to assess the stability of implants placed into the grafted bone, as well as to monitor its changes during the healing period. Methods. The study included 18 patients with a total of 20 grafted sites. The residual alveolar ridge was measured before and after the augmentation and prior to implant placement. All implants were restored with provisional crowns within 48 hours after the placement. Implant stability was assessed using resonance frequency analysis. Results. The average period from ridge augmentation to reentry was 5.4 months (range 4–6 months. At reentry the healed alveolar ridge had a mean width of 6.1 ± 1.27 mm. The mean calculated width gain was 3.04 ± 1.22 mm. The overall surface resorption of block grafts was 0.68 ± 0.69 mm (18.85%. At the time of implant placement the mean value of implant stability quotient (ISQ was 71.25 ± 5.77. The lowest ISQ values were noted after three weeks of healing, followed by a gradual increase until week 12. After 12 weeks implants showed significantly higher ISQ values compared to primary stability (p < 0.05 Wilcoxon signed ranks test. During the 3-years followup period no cases of implant loss were recorded. Conclusion. Despite a significant resorption of bone grafts, it was possible to place implants in all the cases and to use the immediate loading protocol without affecting implant survival rate. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no.175021

  15. Repair of microdamage in osteonal cortical bone adjacent to bone screw.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Up to date, little is known about the repair mode of microdamage in osteonal cortical bone resulting from bone screw implantation. In this study, self-tapping titanium cortical bone screws were inserted into the tibial diaphyses of 24 adult male rabbits. The animals were sacrificed at 1 day, 2 weeks, 1 month and 2 months after surgery. Histomorphometric measurement and confocal microscopy were performed on basic fuchsin stained bone sections to examine the morphological characteristics of microdamage, bone resorption activity and spatial relationship between microdamage and bone resorption. Diffuse and linear cracks were coexisted in peri-screw bone. Intracortical bone resorption was significantly increased 2 weeks after screw installation and reach to the maximum at 1 month. There was no significant difference in bone resorption between 1-month and 2-months groups. Microdamage was significantly decreased within 1 month after surgery. Bone resorption was predisposed to occur in the region of <100 µm from the bone-screw interface, where had extensive diffuse damage mixed with linear cracks. Different patterns of resorption cavities appeared in peri-screw bone. These data suggest that 1 the complex microdamage composed of diffuse damage and linear cracks is a strong stimulator for initiating targeted bone remodeling; 2 bone resorption activities taking place on the surfaces of differently oriented Haversian and Volkmann canals work in a team for the repair of extensive microdamage; 3 targeted bone remodeling is a short-term reaction to microdamage and thereby it may not be able to remove all microdamage resulting from bone screw insertion.

  16. Benign bone tumors

    International Nuclear Information System (INIS)

    Gilday, D.L.; Ash, J.M.

    1976-01-01

    There is little information in the literature concerning the role of bone scanning in benign bone neoplasms except for sporadic reports. Since the advent of /sup 99m/Tc-polyphosphate, bone imaging has proven feasible and useful in locating the cause of bone pain, such as in osteoid osteomas, which are not always radiologically apparent, and in evaluating whether or not a radiologic lesion is indeed benign and solitary. Blood-pool images are particularly important in neoplastic disease, since the absence of hyperemia in the immediate postinjection period favors the diagnosis of a benign neoplasm, as does low-grade uptake on the delayed study. The scan, including pinhole magnification images, is especially valuable in diagnosing lesions in the spine and pelvis, which are poorly seen radiologically. We have studied various types of benign bone tumors, including simple and aneurysmal bone cysts, fibrous cortical defects, and nonossifying fibromas, all of which had minimal or no increased uptake of the radiopharmaceutical, unless traumatized. Although osteochondromas and enchondromas showed varied accumulation of activity, the scan was useful in differentiating these from sarcomatous lesions. All osteoid osteomas demonstrated marked activity, and could be accurately located preoperatively, as could the extent of fibrous dysplasia. The bone scan in the reticuloses also showed abnormal accumulation of activity, and aided in arriving at the prognosis and treatment of histiocytic bone lesions

  17. Is cortical bone hip? What determines cortical bone properties?

    Science.gov (United States)

    Epstein, Sol

    2007-07-01

    Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal

  18. Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Quanwei; Chen, Sixu; Qin, Hao [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Feng, Jianquan [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A& M Health Science Center, Dallas, TX 75246 (United States); Liu, Huayu; Liu, Daocheng; Li, Ang; Shen, Yue; Zhong, Xiaozheng; Li, Junfeng [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Zong, Zhaowen, E-mail: zongzhaowen@sina.cn [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China)

    2017-01-01

    Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-β-catenin mice. Then the effect of CA-β-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength. - Highlights: • Wnt/β-catenin signaling plays a central role in controlling bone mass. • CA-β-catenin has side effects on the bone

  19. An evaluation of the effect of age and the peri-parturient period on bone metabolism in dairy cows as measured by serum bone-specific alkaline phosphatase activity and urinary deoxypyridinoline concentration.

    Science.gov (United States)

    Sato, Reiichiro; Onda, Ken; Kato, Hajime; Ochiai, Hideharu; Kawai, Kazuhiro; Iriki, Tsunenori; Kaneko, Kazuyuki; Yamazaki, Yukio; Wada, Yasunori

    2013-08-01

    Various biochemical markers help to evaluate the state of bone turnover in humans and could be used during the peri-parturient period in dairy cows when calcium (Ca) metabolism changes dramatically. To investigate this, the peri-partum characteristics of serum bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were investigated. Both serum BAP activity and urinary DPD concentrations were increased and demonstrated wide variability in younger animals, and these findings were consistent with other bone turnover markers. Around the time of parturition, serum Ca concentration and serum BAP activity in multiparous cows were significantly lower than in primiparous cows, but urinary DPD concentration was unchanged. The use of BAP as a bone formation marker appears to be valuable for evaluating bone remodelling status in cows, but the specificity of the test needs to be confirmed. The DPD/BAP ratio around parturition demonstrated a clear difference in bone turnover status between the two parity groups with multiparous cows demonstrating increased signs of bone resorption compared with primiparous cows, corresponding to the Ca requirement for milk production. In future studies, the applicability of the ratio of bone resorption marker to bone formation marker should be evaluated for bone turnover assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. The role of lean body mass and physical activity in bone health in children.

    Science.gov (United States)

    Baptista, Fátima; Barrigas, Carlos; Vieira, Filomena; Santa-Clara, Helena; Homens, Pedro Mil; Fragoso, Isabel; Teixeira, Pedro J; Sardinha, Luís B

    2012-01-01

    In the context of physical education curricula, markers of physical fitness (e.g., aerobic capacity, muscular strength, flexibility, and body mass index or body fat) are usually evaluated in reference to health standards. Despite their possible mediating role in the relationship between weight-bearing or muscle forces and features of bone tissue, these attributes of fitness may not be the most relevant to predict skeletal health. It is therefore important to analyze the relative contribution of these factors to the variability in bone tissue of different parts of the skeleton, and to analyze it by gender, as sensitivity to mechanical loading can diverge for boys and girls. We compared the effects of habitual physical activity (PA) and lean mass, as surrogates of weight-bearing and muscle forces, and of physical fitness (aerobic and muscle capacity of lower and upper limbs) on bone mineral content (BMC) and size of total body, lumbar spine, femoral neck, and 1/3 radius in 53 girls and 64 boys from 7.9 to 9.7 years of age. After controlling for bone age, body mass, body height, and calcium intake, lean mass was the most important predictor of bone size and/or mineral in both genders (p  608 counts/min/day (~105 min/day of moderate and vigorous intensity) showed 13-20% more BMC than those with less physical activity, and girls with a lean mass >19 kg showed 12-19% more BMC than those with less lean mass. These findings suggest that lean mass was the most important predictor of bone size and/or mineralization in both genders, while habitual weight-bearing PA appears to positively impact on bone mineral in prepubertal boys and that both lean mass and PA need to be considered in physical education curricula and other health-enhancing programs.

  1. Facilitation of bone resorption activities in synovial lavage fluid patients with mandibular condyle fractures.

    Science.gov (United States)

    Takano, H; Takahashi, T; Nakata, A; Nogami, S; Yusa, K; Kuwajima, S; Yamazaki, M; Fukuda, M

    2016-05-01

    The aim of this study was to investigate the bone resorption effect of the mediators delivered in joint cavity of patients with mandibular condyle fractures by detecting osteoclast markers using cellular biochemistry methods, and by analysing bone resorption activities via inducing osteoclast differentiation of the infiltrated cells from arthrocentesis. Sixteen joints in 10 patients with mandibular condyle fractures were evaluated. The control group consisted of synovial fluid (SF) samples from seven joints of four volunteers who had no clinical signs or symptoms involving the temporomandibular joint (TMJ) or disc displacement. We collected SF cells from all patients during therapeutic arthrocentesis. The infiltrating cells from TMJ SF were cultured, differentiated into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and examined bone resorption activities. We also investigated factors related to osteoclast induction of SF, using ELISA procedures. Osteoclast-like cells were induced from the SF cells obtained from all patients with condylar fractures. These multinucleated giant cells were positive for TRAP and actin, and had the ability to absorb dentin slices. The levels of macrophage colony-stimulating factor (M-CSF), prostaglandin E2 (PGE2), soluble form of receptor activator of nuclear factor kappa-B ligand (sRANKL) and osteoprotegerin (OPG), in SF samples from the patients, were significantly higher than in the controls. These findings indicate that bone resorption activities in SF from patients with mandibular condyle fractures were upregulated and may participate in the pathogenesis and wound healing. © 2016 The Authors. Journal of Oral Rehabilitation Published by John Wiley & Sons Ltd.

  2. Intraoperative bone and bone marrow sampling: a simple method for accurate measurement of uptake of radiopharmaceuticals in bone and bone marrow

    International Nuclear Information System (INIS)

    Oyen, W.J.G.; Buijs, W.C.A.M.; Kampen, A. van; Koenders, E.B.; Claessens, R.A.M.J.; Corstens, F.H.M.

    1993-01-01

    Accurate estimation of bone marrow uptake of radiopharmaceuticals is of crucial importance for accurate whole body dosimetry. In this study, a method for obtaining normal bone marrow and bone during routine surgery without inconvenience to volunteers is suggested and compared to an indirect method. In five volunteers (group 1), 4 MBq 111 In-labelled human polyclonal IgG ( 111 In-IgG) was administered 48h before placement of a total hip prosthesis. After resection of the femoral head and neck, bone marrow was aspirated from the medullary space with a biopsy needle. In five patients, suspected of having infectious disease (group 2), bone marrow uptake was calculated according to a well-accepted method using regions of interest over the lumbar spine, 48h after injection of 75 MBq 111 In-IgG. Bone marrow uptake in group 1 (4.5 ±1.3%D kg -1 ) was significantly lower than that in group 2 (8.5 ± 2.1%D kg -1 ) (P<0.01). Blood and plasma activity did not differ significantly for both groups. This method provides a system for directly and accurately measuring uptake and retention in normal bone marrow and bone of all radiopharmaceuticals at various time points. It is a safe and simple procedure without any discomfort to the patient. Since small amounts of activity are sufficient, the radiation dose to the patient is low. (author)

  3. Resorbable electrospun polydioxanone fibres modify the behaviour of cells from both healthy and diseased human tendons

    Directory of Open Access Journals (Sweden)

    A Kendal

    2017-02-01

    Full Text Available Chronic tendinopathy in an active and ageing population represents an increasing burden to healthcare systems. Rotator cuff tendinopathy alone accounts for approximately 70 % of all shoulder pain. Tendinopathic tissue has a disorganised extracellular matrix, altered vasculature, and infiltration of fibroblasts and inflammatory cells. This altered biology may contribute to the limited success of surgical repair strategies. Electrospun resorbable scaffolds can potentially enhance endogenous repair mechanisms by influencing the tissue microenvironment. Polydioxanone (PDO has an established safety profile in patients. We compared the response of healthy and diseased human tendon cells to electrospun PDO fibres using live cell imaging, proliferation, flow cytometry, and gene expression studies. Within 4 h of initial contact with electrospun PDO, healthy tendon cells underwent a marked transformation; elongating along the fibres in a fibre density dependent manner. Diseased tendon cells initially responded at a slower rate, but ultimately underwent a similar morphological change. Electrospun fibres increased the proliferation rate of diseased tendon cells and increased the ratio of type I:IIIcollagenmRNA expression. Flow cytometry revealed decreased expression of CD106, a marker of mesenchymal stem cells, and increased expression of CD10 on healthy versus diseased tendon cells. PDO electrospun scaffolds further promoted CD106negCD10pos expression of healthy tendon cells. Despite their behavioural differences, both healthy and diseased human tendon cells responded to electrospun PDO fibres. This encourages further work establishing their efficacy in augmenting surgical repair of diseased tendons.

  4. Dioxin-induced up-regulation of the active form of vitamin D is the main cause for its inhibitory action on osteoblast activities, leading to developmental bone toxicity

    International Nuclear Information System (INIS)

    Nishimura, Noriko; Nishimura, Hisao; Ito, Tomohiro; Miyata, Chie; Izumi, Keiko; Fujimaki, Hidekazu; Matsumura, Fumio

    2009-01-01

    Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is known to cause bone toxicity, particularly during animal development, although its action mechanism to cause this toxicity has yet to be elucidated. Mouse pups were exposed to TCDD via dam's milk that were administered orally with 15 μg TCDD/kg b.w. on postnatal day 1. Here we report that TCDD causes up-regulation of vitamin D 1α-hydroxylase in kidney, resulting in a 2-fold increase in the active form of vitamin D, 1,25-dihydroxyvitamin D 3 , in serum. This action of TCDD is not caused by changes in parathyroid hormone, a decrease in vitamin D degrading enzyme, vitamin D 24-hydroxylase, or alterations in serum Ca 2+ concentration. Vitamin D is known to affect bone mineralization. Our data clearly show that TCDD-exposed mice exhibit a marked decrease in osteocalcin and collagen type 1 as well as alkaline phosphatase gene expression in tibia by postnatal day 21, which is accompanied with a mineralization defect in the tibia, lowered activity of osteoblastic bone formation, and an increase in fibroblastic growth factor-23, a sign of increased vitamin D effect. Despite these significant effects of TCDD on osteoblast activities, none of the markers of osteoclast activities was found to be affected. Histomorphometry confirmed that osteoblastic activity, but not bone resorption activity, was altered by TCDD. A prominent lesion commonly observed in these TCDD-treated mice was impaired bone mineralization that is characterized by an increased volume and thickness of osteoids lining both the endosteum of the cortical bone and trabeculae. Together, these data suggest that the impaired mineralization resulting from reduction of the osteoblastic activity, which is caused by TCDD-induced up-regulation of vitamin D, is responsible for its bone developmental toxicity.

  5. Bropirimine inhibits osteoclast differentiation through production of interferon-β

    International Nuclear Information System (INIS)

    Suzuki, Hiroaki; Mochizuki, Ayako; Yoshimura, Kentaro; Miyamoto, Yoichi; Kaneko, Kotaro; Inoue, Tomio; Chikazu, Daichi; Takami, Masamichi; Kamijo, Ryutaro

    2015-01-01

    Bropirimine is a synthetic agonist for toll-like receptor 7 (TLR7). In this study, we investigated the effects of bropirimine on differentiation and bone-resorbing activity of osteoclasts in vitro. Bropirimine inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) induced by receptor activator of nuclear factor κB ligand (RANKL) in a concentration-dependent manner. Furthermore, it suppressed the mRNA expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), a master transcription factor for osteoclast differentiation, without affecting BMM viability. Bropirimine also inhibited osteoclast differentiation induced in co-cultures of mouse bone marrow cells (BMCs) and mouse osteoblastic UAMS-32 cells in the presence of activated vitamin D_3. Bropirimine partially suppressed the expression of RANKL mRNA in UAMS-32 cells induced by activated vitamin D_3. Finally, the anti-interferon-β (IFN-β) antibody restored RANKL-dependent differentiation of BMMs into osteoclasts suppressed by bropirimine. These results suggest that bropirimine inhibits differentiation of osteoclast precursor cells into osteoclasts via TLR7-mediated production of IFN-β.

  6. Bropirimine inhibits osteoclast differentiation through production of interferon-β

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Hiroaki [Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Mochizuki, Ayako [Department of Oral Physiology, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Yoshimura, Kentaro; Miyamoto, Yoichi [Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Kaneko, Kotaro [Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023 (Japan); Inoue, Tomio [Department of Oral Physiology, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Chikazu, Daichi [Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo 160-0023 (Japan); Takami, Masamichi [Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555 (Japan); Kamijo, Ryutaro, E-mail: kamijor@dent.showa-u.ac.jp [Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555 (Japan)

    2015-11-06

    Bropirimine is a synthetic agonist for toll-like receptor 7 (TLR7). In this study, we investigated the effects of bropirimine on differentiation and bone-resorbing activity of osteoclasts in vitro. Bropirimine inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) induced by receptor activator of nuclear factor κB ligand (RANKL) in a concentration-dependent manner. Furthermore, it suppressed the mRNA expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), a master transcription factor for osteoclast differentiation, without affecting BMM viability. Bropirimine also inhibited osteoclast differentiation induced in co-cultures of mouse bone marrow cells (BMCs) and mouse osteoblastic UAMS-32 cells in the presence of activated vitamin D{sub 3}. Bropirimine partially suppressed the expression of RANKL mRNA in UAMS-32 cells induced by activated vitamin D{sub 3}. Finally, the anti-interferon-β (IFN-β) antibody restored RANKL-dependent differentiation of BMMs into osteoclasts suppressed by bropirimine. These results suggest that bropirimine inhibits differentiation of osteoclast precursor cells into osteoclasts via TLR7-mediated production of IFN-β.

  7. Determination of trace cadmium and other elements in bone by epithermal neutron activation analysis

    International Nuclear Information System (INIS)

    Dowlati, R.; Jervis, R.E.

    1991-01-01

    Epithermal neutron activation analysis (ENAA) was applied to measure quantitatively Cd and other elements in bone samples from control and Cd-fed rats. This method was found to be non-destructive to the bone samples, with no sign of 'radiolytic charring' and was sensitive enough to detect and quantify Cd in bone samples at normal levels for mammals (viz. 0.5-1.0μg/g) and higher. Two different thermal neutron shield materials were utilized, namely cadmium and boron. The boron shield resulted in a 27% improvement in the detection limit of Cd in bone. The accuracy of ENAA for Cd was assessed by intercomparison with electrothermal atomic absorption spectrophotometry (ETAAS), and the results were in fair agreement (±23%) with those from ENAA. (author) 24 refs.; 5 tabs

  8. The role of daily physical activity and nutritional status on bone turnover in cystic fibrosis: a cross-sectional study

    OpenAIRE

    Tejero,Sergio; Cejudo,Pilar; Quintana-Gallego,E.; Sañudo,Borja; Oliva-Pascual-Vaca,A.

    2016-01-01

    ABSTRACT Background Nutritional status and daily physical activity (PA) may be an excellent tool for the maintenance of bone health in patients with cystic fibrosis (CF). Objective To evaluate the relationship between nutritional status, daily physical activity and bone turnover in cystic fibrosis patients. Method A cross-sectional study of adolescent and adult patients diagnosed with clinically stable cystic fibrosis was conducted. Total body, femoral neck, and lumbar spine bone mineral d...

  9. [Frontier in bone biology].

    Science.gov (United States)

    Takeda, Shu

    2015-10-01

    Bone is an active organ in which bone mass is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption, i.e., coupling of bone formation and bone resorption. Recent advances in molecular bone biology uncovered the molecular mechanism of the coupling. A fundamental role of osteocyte in the maintenance of bone mass and whole body metabolism has also been revealed recently. Moreover, neurons and neuropeptides have been shown to be intimately involved in bone homeostasis though inter-organ network, in addition to "traditional" regulators of bone metabolism such as soluble factors and cytokines

  10. Analysis of Bone Meal (NIST 1486) and Bone Ash (NIST 1400) reference materials by neutron activation method; Analise de materiais de referencia Bone Meal (NIST 1486) e Bone Ash (NIST 1400) pelo metodo de ativacao com neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Takata, Marcelo K.; Saiki, Mitiko [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil); Borelli, Aurelio [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina

    1999-11-01

    In this work instrumental neutron activation analysis has been applied to determine Ba, ca, Cl, Cr, fe, Mg, Mn, Na, P, Sb, Sc, Sr and Zn in two biological reference materials NIST 1486 Bone Meal and NIST 1400 Bone Ash. The purpose of this work was to evaluate the precision and the accuracy of the results as well as to give a contribution to certificate these materials. Interferences found in the determination of some elements were also discussed. (author) 8 refs., 4 tabs.

  11. A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration.

    Science.gov (United States)

    Yassin, Mohammed A; Mustafa, Kamal; Xing, Zhe; Sun, Yang; Fasmer, Kristine Eldevik; Waag, Thilo; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Leknes, Knut N

    2017-06-01

    Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-ε-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Relationship between Bone-Specific Physical Activity Scores and Measures for Body Composition and Bone Mineral Density in Healthy Young College Women.

    Directory of Open Access Journals (Sweden)

    SoJung Kim

    Full Text Available The purpose of this cross-sectional study was to investigate the relationship between bone-specific physical activity (BPAQ scores, body composition, and bone mineral density (BMD in healthy young college women.Seventy-three college women (21.7 ± 1.8 years; 162.1 ± 4.6 cm; 53.9 ± 5.8 kg between the ages of 19 and 26 years were recruited from the universities in Seoul and Gyeonggi province, South Korea. We used dual energy X-ray absorptiometry to measure the lumbar spine (L2-L4 and proximal femur BMD (left side; total hip, femoral neck. The BPAQ scores (past, pBPAQ; current, cBPAQ; total, tBPAQ were used to obtain a comprehensive account of lifetime physical activity related to bone health. We used X-scan plus II instrumentation to measure height (cm, weight (kg, fat free mass (FFM, kg, percent body fat (%, and body mass index (BMI. Participants were asked to record their 24-hour food intake in a questionnaire.There were positive correlations between BPAQ scores and total hip (pBPAQ r = 0.308, p = 0.008; tBPAQ, r = 0.286, p = 0.014 and FN BMD (pBPAQ r = 0.309, p = 0.008; tBPAQ, r = 0.311, p = 0.007, while no significant relationships were found in cBPAQ (p > 0.05. When FFM, Vitamin D intake, cBPAQ, pBPAQ, and tBPAQ were included in a stepwise multiple linear regression analysis, FFM and pBPAQ were predictors of total hip, accounting for 16% (p = 0.024, while FFM and tBPAQ predicted 14% of the variance in FN (p = 0.015. Only FFM predicted 15% of the variance in L2-L4 (p = 0.004. There was a positive correlation between Vitamin D intake and L2-L4 (p = 0.025, but other dietary intakes variables were not significant (p > 0.05.BPAQ-derived physical activity scores and FFM were positively associated with total hip and FN BMD in healthy young college women. Our study suggests that osteoporosis awareness and effective bone healthy behaviors for college women are required to prevent serious bone diseases later in life.

  13. Bone loss in rheumatoid arthritis. Influence of disease activity, duration of the disease, functional capacity, and corticosteroid treatment

    DEFF Research Database (Denmark)

    Hansen, M; Florescu, A; Stoltenberg, M

    1996-01-01

    Axial and appendicular bone mass were studied in 95 patients with rheumatoid arthritis. The aims were to quantify bone mineral density (BMD) and to evaluate the importance of disease activity, duration of disease, functional capacity, and corticosteroid treatment for bone loss in patients...... after the start of the disease. The overall functional capacity in terms of physical activity increased BMD in the axial skeleton. The local functional capacity in terms of grip strength was positively related to BMD in the appendicular skeleton. Patients with severe functional impairment had the lowest...

  14. Hypoxia inducible factor-1 is activated by transcriptional co-activator with PDZ-binding motif (TAZ) versus WWdomain-containing oxidoreductase (WWOX) in hypoxic microenvironment of bone metastasis from breast cancer.

    Science.gov (United States)

    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Luzzati, Alessandro; Perrucchini, Giuseppe; Desiderio, Maria Alfonsina

    2013-07-01

    The hypoxic microenvironment of bone marrow favours the bone metastasis process. Hypoxia inducible factor (HIF)-1α is hallmark for hypoxia, correlating with poor prognosis and radio/chemotherapy resistance of primary-breast carcinoma. For bone metastasis, the molecular mechanisms involved in HIF-1α expression and HIF-1 (α/β heterodimer)-transcription factor activity are scarcely known. We studied the role played by HIF-1 in the cross-talk between neoplastic and supportive-microenvironmental cells. Also, WWdomain-containing oxidoreductase (Wwox) and transcriptional co-activator with PDZ-binding motif (TAZ) were taken into consideration evaluating whether these Hippo-pathway effectors affect bone-metastatic phenotype through HIF-1 activity. Considering bone-metastasis specimens, nuclear HIF-1α-TAZ co-localisation occurred in neoplastic and supportive cells, such as fibroblasts and endotheliocytes. Based on these data, the functional importance was verified using 1833-bone metastatic clone under hypoxia: nuclear HIF-1α and TAZ expression increased and co-immunoprecipitated, activating HIF-1-DNA binding and transactivation. In contrast, Wwox localised at perinuclear level in neoplastic cells of bone metastasis, being almost absent in supportive cells, and Wwox-protein expression diminished in hypoxic-1833 cells. Thus, TAZ regulation of HIF-1 activity might be important for bone-secondary growth, participating in metastasis-stroma cross-talk. Further, TAZ and HIF-1α-protein levels seemed correlated. In fact, blocking cyclooxygenase-2 with NS398 in hypoxic-1833 cells, not only HIF-1α decreased but also molecular-mechanism(s) upstream of the Hippo pathway were triggered: LATS-dependent TAZ phosphorylation seemed responsible for TAZ nucleus/cytoplasm translocation and degradation. In the 1833-xenograft model, NS398 largely prevented the outgrowth of bone-metastatic cells, probably related to remarkable-extracellular matrix assembly. We gained clinical insight into

  15. Polycythemia is associated with bone loss and reduced osteoblast activity in mice.

    Science.gov (United States)

    Oikonomidou, P R; Casu, C; Yang, Z; Crielaard, B; Shim, J H; Rivella, S; Vogiatzi, M G

    2016-04-01

    Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO). PV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO. Bone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2(V617F) knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO. Compared to wt, both JAK2(V617F) and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated.

  16. SU-E-J-250: A Methodology for Active Bone Marrow Protection for Cervical Cancer Intensity-Modulated Radiotherapy Using 18F-FLT PET/CT Image

    International Nuclear Information System (INIS)

    Ma, C; Yin, Y

    2014-01-01

    Purpose: The purpose of this study was to compare a radiation therapy treatment planning that would spare active bone marrow and whole pelvic bone marrow using 18F FLT PET/CT image. Methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using 18F FLT/CT scans. Plans were generated for two cervical cancer patients, where pelvicactive bone marrow region was incorporated as avoidance regions based on the range: SUV>2., another region was whole pelvic bone marrow. Dose objectives were set to reduce the volume of active bone marrow and whole bone marraw. The volumes of received 10 (V10) and 20 (V20) Gy for active bone marrow were evaluated. Results: Active bone marrow regions identified by 18F FLT with an SUV>2 represented an average of 48.0% of the total osseous pelvis for the two cases studied. Improved dose volume histograms for identified bone marrow SUV volumes and decreases in V10(average 18%), and V20(average 14%) were achieved without clinically significant changes to PTV or OAR doses. Conclusion: Incorporation of 18F FLT/CT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in cervical cancer

  17. Characterisation of Bone Beneficial Components from Australian Wallaby Bone

    Science.gov (United States)

    Lao, Weiguo; Jin, Xingliang; Tan, Yi; Xiao, Linda; Padula, Matthew P.; Bishop, David P.; Reedy, Brian; Ong, Madeleine; Kamal, Mohammad A.; Qu, Xianqin

    2016-01-01

    Background: Osteoporosis is a condition in which the bones become brittle, increasing the risk of fractures. Complementary medicines have traditionally used animal bones for managing bone disorders, such as osteoporosis. This study aimed to discover new natural products for these types of conditions by determining mineral and protein content of bone extracts derived from the Australian wallaby. Methods: Inductively coupled plasma-mass spectrometry and Fourier transform infrared spectroscopic analysis were used for mineral tests, proteome analysis was using LC/MS/MS and the effects of wallaby bone extracts (WBE)s on calcium deposition and alkaline phosphatase activity were evaluated in osteogenic cells derived from adipose tissue-derived stem cells (ADSCs). Results: Concentrations of calcium and phosphorus were 26.21% and 14.72% in WBE respectively. Additionally, minerals found were wide in variety and high in concentration, while heavy metal concentrations of aluminium, iron, zinc and other elements were at safe levels for human consumption. Proteome analysis showed that extracts contained high amounts of bone remodelling proteins, such as osteomodulin, osteopontin and osteoglycin. Furthermore, in vitro evaluation of WBEs showed increased deposition of calcium in osteoblasts with enhanced alkaline phosphatase activity in differentiated adipose-derived stem cells. Conclusion: Our results demonstrate that wallaby bone extracts possess proteins and minerals beneficial for bone metabolism. WBEs may therefore be used for developing natural products for conditions such as osteoporosis and further investigation to understand biomolecular mechanism by which WBEs prevent osteoporosis is warranted. PMID:28930133

  18. Trace element concentrations in human bone using instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    El-Amri, F.A.; El-Kabroun, M.A.R.

    1997-01-01

    Instrumental neutron activation analysis has been applied to analyze 23 bone samples obtained from Libyan patient aged (3-80) years for the study of the concentration levels of trace elements Ba, Br, Ca, Fe, Sr and Zn and their concentration patterns regarding to the age and sex of the patients. (author)

  19. Physical activity and dark skin tone: protective factors against low bone mass in Mexican men.

    Science.gov (United States)

    Vivanco-Muñoz, Nalleli; Jo, Talavera; Gerardo, Huitron-Bravo; Juan, Tamayo; Clark, Patricia

    2012-01-01

    A cross-sectional study was conducted on 268 Mexican men between the ages of 13 and 80 yr to evaluate the association of clinical factors related with bone mass. Men from high schools, universities, and retirement homes were invited to participate. Body mass index (BMI) was measured, and bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry for L1-L4 and total hip. Factors related to bone mass were assessed by questionnaire and analyzed using a logistic regression model. Demographic factors (age, education, and occupation), clinical data (BMI, skin tone, previous fracture, history of osteoporosis [OP], and history of fractures), and lifestyle variables (diet, physical activity, sun exposure, and smoking) were evaluated. Physical activity (≥ 60 min/5 times a week) reduced the risk for low BMD for age, osteopenia, and OP at the spine and total hip (odds ratio [OR]: 0.276; 95% confidence interval [CI]: 0.099-0.769; p=0.014; and OR: 0.184; 95% CI: 0.04-0.849; p=0.03, respectively). Dark skin tone was a protective factor, decreasing the risk by up to 70%. In this population of healthy Mexican men (aged 13-80 yr), dark skin and physical activity were protective factors against low bone mass. Copyright © 2012 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  20. Secondary osteoporosis.

    Science.gov (United States)

    Boyle, I T

    1993-10-01

    Osteoporosis with attendant increased fracture risk is a common complication of many other diseases. Indeed, almost all chronic diseases make some impact on life-style, usually by restricting physical activity and hence reducing the anabolic effect of exercise and gravitational strains on the skeleton. Restricted appetite and modified gastrointestinal tract function is another commonplace finding that has an impact on bone nutrition and synthesis, as on other systems. Sex hormone status is of particular importance for the maintenance of the normal skeleton, and the postmenopausal woman is at particular risk for most causes of secondary osteoporosis. In dealing with secondary osteoporosis in the hypo-oestrogenic woman, the question of giving hormone replacement therapy in addition to other disease-specific therapy should always be considered, as, for example, in a young amenorrhoeic woman with Crohn's disease. Similarly, in hypogonadal men the administration of testosterone is useful for bone conservation. The wider availability of bone densitometry ought to make us more aware of the presence of osteoporosis in the many disease states discussed above. This is particularly important as the life span of such patients is now increased by improved management of the underlying disease process in many instances. Even in steroid-induced osteoporosis--one of the commonest and most severe forms of osteoporosis--we now have some effective therapy in the form of the bisphosphonates and other anti-bone-resorbing drug classes. The possibility of prophylaxis against secondary osteoporosis has therefore become a possibility, although the very long-term effects of such drug regimens are still unknown. In some situations, such as thyrotoxicosis, Cushing's syndrome and immobilization, spontaneous resolution of at least part of the osteoporosis is possible after cure of the underlying problem. The shorter the existence of the basic problem, the more successful the restoration of the

  1. Influence of muscle strength, physical activity and weight on bone mass in a population-based sample of 1004 elderly women.

    Science.gov (United States)

    Gerdhem, P; Ringsberg, K A M; Akesson, K; Obrant, K J

    2003-09-01

    High physical activity level has been associated with high bone mass and low fracture risk and is therefore recommended to reduce fractures in old age. The aim of this study was to estimate the effect of potentially modifiable variables, such as physical activity, muscle strength, muscle mass and weight, on bone mass in elderly women. The influence of isometric thigh muscle strength, self-estimated activity level, body composition and weight on bone mineral density (dual energy X-ray absorptiometry; DXA) in total body, hip and spine was investigated. Subjects were 1004 women, all 75 years old, taking part in the Malmö Osteoporosis Prospective Risk Assessment (OPRA) study. Physical activity and muscle strength accounted for 1-6% of the variability in bone mass, whereas weight, and its closely associated variables lean mass and fat mass, to a much greater extent explained the bone mass variability. We found current body weight to be the variable with the most substantial influence on the total variability in bone mass (15-32% depending on skeletal site) in a forward stepwise regression model. Our findings suggest that in elderly women, the major fracture-preventive effect of physical activity is unlikely to be mediated through increased bone mass. Retaining or even increasing body weight is likely to be beneficial to the skeleton, but an excess body weight increase may have negative effects on health. Nevertheless, training in elderly women may have advantages by improving balance, co-ordination and mobility and therefore decreasing the risk of fractures.

  2. The use of bone scintigraphy to detect active Hansen's disease in mutilated patients

    Energy Technology Data Exchange (ETDEWEB)

    Braga, F.J.H.N. [Seccao de Medicina Nuclear do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, USP (Brazil); Departamento de Fisica e Biofisica, Instituto de Biociencias, UNESP, Botucato (Brazil); Foss, N.T.; Ferriolli, E. [Departamento de Clinica Medica da Faculdade de Medicina de Ribeirao Preto, USP (Brazil); Pagnano, C. [Secretaria da Saude, Ribeirao Preto (Brazil); Miranda, J.R.A.; De Moraes, R. [Departamento de Fisica e Biofisica, Instituto de Biociencias, UNESP, Botucato (Brazil)

    1999-11-01

    Mutilation of extremities was very frequent in patients affected by leprosy in the past; although it is now much less common, it is still seen, mainly in patients with long-term disease. In general, mutilation of the nose and ears is caused by the bacillus and mutilation of the hands and feet a consequence of chronic trauma. Leprosy must be chronically treated and any decision to interrupt therapy is based on laboratory tests and biopsy. Scintigraphy is a non-invasive procedure which could be of great value in to determining disease activity. We studied eight patients (five males and three females, aged 64-73 years) who presented with mutilation of the nose (2), ear (1), feet (3) or foot and hand (2). Conventional three-phase bone scintigraphy (750 MBq) and X-ray examinations of the affected areas were performed in all patients. Bone scintigraphy was abnormal in four patients (the presence of bacilli was confirmed by biopsy in two of them), and normal in the other four. In all patients except for the one with ear mutilation, radiography only showed the absence of bone. We conclude that bone scintigraphy is very useful to determine disease activity in cases of mutilation caused by leprosy. It seems to be superior to conventional radiography and may enable bone biopsies to be avoided. (orig.)

  3. Mice with cancer-induced bone pain show a marked decline in day/night activity

    Directory of Open Access Journals (Sweden)

    Lisa A. Majuta

    2017-10-01

    Conclusion:. Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status.

  4. Characterization of human erythroid burst-promoting activity derived from bone marrow conditioned media

    International Nuclear Information System (INIS)

    Porter, P.N.; Ogawa, M.

    1982-01-01

    Bone marrow conditioned media (BMCM) increases burst number and the incorporation of 59 Fe into heme by bursts when peripheral blood or bone marrow cells are cultured at limiting serum concentrations. Burst-promoting activity (BPA) has now been purified approximately 300-fold from this source by ion-exchange chromatography on DEAE-Sephadex and absorption chromatography on hydroxyapatite agarose gel. Marrow BPA increased burst number and hemoglobin (Hb) synthesis in a dose-dependent manner. A larger increase in Hb synthesis than in burst number was consistently observed, which was probably a consequence of the increase in the number of cells per burst that occurs in the presence of BPA. The role of BPA in culture could be distinguished from erythropoietin (Ep), since no bursts grew in the absence of Ep, whether or not BPA was present, and since it had no effect on the growth of erythroid colonies scored at day 5 of culture. Our purified fraction did not support the growth of CFU-C in culture. Activity was stable at temperatures of 70 degrees C or lower for 10 min; exposure to 80 degrees C resulted in approximately 50% loss of activity. BPA was completely inactivated by treatment at 100 degrees C for 10 min. Thus, human bone marrow cells produce a heat-sensitive factor that specifically promotes the growth of early erythroid progenitors in culture

  5. Novel anti-cancer strategy in bone tumors by targeting molecular and cellular modulators of bone resorption.

    Science.gov (United States)

    Brounais, Bénédicte; Ruiz, Carmen; Rousseau, Julie; Lamoureux, François; Blanchard, Frédéric; Heymann, Dominique; Redini, Françoise

    2008-11-01

    Tumor cells alter the balanced process of bone formation and bone resorption mediated respectively by osteoblasts and osteoclasts, leading to the disruption of the normal equilibrium and resulting in a spectrum of osteolytic to osteoblastic lesions. This review will summarize research on molecules that play direct and essential roles in the differentiation and activity of osteoclasts, and the role of these molecules in bone destruction caused by cancer. Results from experimental models suggest that the Receptor Activator of NF-kB Ligand (RANKL), a member of the TNF superfamily is a common effector of bony lesions in osteolysis caused by primary and secondary bone tumors. Therefore, osteoclast represents an attractive target across a broad range of tumors that develop in bone. Elucidation of the mechanisms of RANKL interactions with its activator (RANK) and decoy (osteoprotegerin: OPG) receptors has enable the development of pharmacological inhibitors of RANKL (and of its signalling pathway) which have been recently patented, with potential for the treatment of cancer-induced bone disease. Blocking bone resorption by specific other drugs such as bisphosphonates, inhibitors of cathepsin K (the main enzyme involved in bone resorption mechanisms) or signalling pathways regulating osteoclast differentiation and activation is also a promising target for the treatment of osteolysis associated to bone tumors.

  6. Kinetic examination of femoral bone modeling in broilers.

    Science.gov (United States)

    Prisby, R; Menezes, T; Campbell, J; Benson, T; Samraj, E; Pevzner, I; Wideman, R F

    2014-05-01

    Lameness in broilers can be associated with progressive degeneration of the femoral head leading to femoral head necrosis and osteomyelitis. Femora from clinically healthy broilers were dissected at 7 (n = 35, 2), 14 (n = 32), 21 (n = 33), 28 (n = 34), and 42 (n = 28) d of age, and were processed for bone histomorphometry to examine bone microarchitecture and bone static and dynamic properties in the secondary spongiosa (IISP) of the proximal femoral metaphysis. Body mass increased rapidly with age, whereas the bone volume to tissue volume ratio remained relatively consistent. The bone volume to tissue volume ratio values generally reflected corresponding values for both mean trabecular thickness and mean trabecular number. Bone metabolism was highest on d 7 when significant osteoblast activity was reflected by increased osteoid surface to bone surface and mineralizing surface per bone surface ratios. However, significant declines in osteoblast activity and bone formative processes occurred during the second week of development, such that newly formed but unmineralized bone tissue (osteoid) and the percentages of mineralizing surfaces both were diminished. Osteoclast activity was elevated to the extent that measurement was impossible. Intense osteoclast activity presumably reflects marked bone resorption throughout the experiment. The overall mature trabecular bone volume remained relatively low, which may arise from extensive persistence of chondrocyte columns in the metaphysis, large areas in the metaphysis composed of immature bone, destruction of bone tissue in the primary spongiosa, and potentially reduced bone blood vessel penetration that normally would be necessary for robust development. Delayed bone development in the IISP was attributable to an uncoupling of osteoblast and osteoclast activity, whereby bone resorption (osteoclast activity) outpaced bone formation (osteoblast activity). Insufficient maturation and mineralization of the IISP may contribute

  7. Transforming growth factor-β inhibits CCAAT/enhancer-binding protein expression and PPARγ activity in unloaded bone marrow stromal cells

    International Nuclear Information System (INIS)

    Ahdjoudj, S.; Kaabeche, K.; Holy, X.; Fromigue, O.; Modrowski, D.; Zerath, E.; Marie, P.J.

    2005-01-01

    The molecular mechanisms regulating the adipogenic differentiation of bone marrow stromal cells in vivo remain largely unknown. In this study, we investigated the regulatory effects of transforming growth factor beta-2 (TGF-β2) on transcription factors involved in adipogenic differentiation induced by hind limb suspension in rat bone marrow stromal cells in vivo. Time course real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of gene expression showed that skeletal unloading progressively increases the expression of CCAAT/enhancer-binding protein (C/EBP)α and C/EBPβ α at 5 days in bone marrow stromal cells resulting in increased peroxisome proliferator-activated receptor γ (PPARγ2) transcripts at 7 days. TGF-β2 administration in unloaded rats corrected the rise in C/EBPα and C/EBPβ transcripts induced by unloading in bone marrow stromal cells. This resulted in inhibition of PPARγ2 expression that was associated with increased Runx2 expression. Additionally, the inhibition of C/EBPα and C/EBPβ expression by TGF-β2 was associated with increased PPARγ serine phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPARγ transactivating activity. The sequential inhibitory effect of TGF-β2 on C/EBPα, C/EBPβ, and PPARγ2 resulted in reduced LPL expression and abolition of bone marrow stromal cell adipogenic differentiation, which contributed to prevent bone loss induced by skeletal unloading. We conclude that TGF-β2 inhibits the excessive adipogenic differentiation of bone marrow stromal cells induced by skeletal unloading by inhibiting C/EBPα, C/EBPβ, and PPARγ expression and activity, which provides a sequential mechanism by which TGF-β2 regulates adipogenic differentiation of bone marrow stromal cells in vivo

  8. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation

    Energy Technology Data Exchange (ETDEWEB)

    Ming, Wei, E-mail: weiming@xiyi.edu.cn [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Department of Pharmacology, Xi’an Medical University, Xi’an 710021 (China); Lu, Gan, E-mail: leonming99@163.com [Department of Gynecology of Shaanxi Provincial People’s Hospital, Xi’an, 710068 (China); Xin, Sha, E-mail: 248967979@qq.com [Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Huanyu, Lu, E-mail: 2366927258@qq.com [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an 710032 (China); Yinghao, Jiang, E-mail: jiangyh@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Xiaoying, Lei, E-mail: leixiaoy@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Chengming, Xu, E-mail: chengmingxu@yeah.net [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Banjun, Ruan, E-mail: running@163.com [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); Li, Wang, E-mail: wanglifw@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China); and others

    2016-08-05

    Therapeutic targeting bone loss has been the focus of the study in osteoporosis. The present study is intended to evaluate whether MOTS-c, a novel mitochondria related 16 aa peptide, can protect mice from ovariectomy-induced osteoporosis. After ovary removal, the mice were injected with MOTS-c at a dose of 5 mg/kg once a day for 12 weeks. Our results showed that MOTS-c treatment significantly alleviated bone loss, as determined by micro-CT examination. Mechanistically, we found that the receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclast differentiation was remarkably inhibited by MOTS-c. Moreover, MOTS-c increased phosphorylated AMPK levels, and compound C, an AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis. Thus, our findings provide evidence that MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis. -- Highlights: •MOTS-c decreases OVX-induced bone loss in vivo. •MOTS-c inhibits RANKL-induced osteoclast formation. •MOTS-c inhibits RANKL-induced osteoclast-specific gene expression. •MOTS-c represses osteoclast differentiation via the activation of AMPK.

  9. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation

    International Nuclear Information System (INIS)

    Ming, Wei; Lu, Gan; Xin, Sha; Huanyu, Lu; Yinghao, Jiang; Xiaoying, Lei; Chengming, Xu; Banjun, Ruan; Li, Wang

    2016-01-01

    Therapeutic targeting bone loss has been the focus of the study in osteoporosis. The present study is intended to evaluate whether MOTS-c, a novel mitochondria related 16 aa peptide, can protect mice from ovariectomy-induced osteoporosis. After ovary removal, the mice were injected with MOTS-c at a dose of 5 mg/kg once a day for 12 weeks. Our results showed that MOTS-c treatment significantly alleviated bone loss, as determined by micro-CT examination. Mechanistically, we found that the receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclast differentiation was remarkably inhibited by MOTS-c. Moreover, MOTS-c increased phosphorylated AMPK levels, and compound C, an AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis. Thus, our findings provide evidence that MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis. -- Highlights: •MOTS-c decreases OVX-induced bone loss in vivo. •MOTS-c inhibits RANKL-induced osteoclast formation. •MOTS-c inhibits RANKL-induced osteoclast-specific gene expression. •MOTS-c represses osteoclast differentiation via the activation of AMPK.

  10. Tissue engineering of ligaments: a comparison of bone marrow stromal cells, anterior cruciate ligament, and skin fibroblasts as cell source.

    Science.gov (United States)

    Van Eijk, F; Saris, D B F; Riesle, J; Willems, W J; Van Blitterswijk, C A; Verbout, A J; Dhert, W J A

    2004-01-01

    Anterior cruciate ligament (ACL) reconstruction surgery still has important problems to overcome, such as "donor site morbidity" and the limited choice of grafts in revision surgery. Tissue engineering of ligaments may provide a solution for these problems. Little is known about the optimal cell source for tissue engineering of ligaments. The aim of this study is to determine the optimal cell source for tissue engineering of the anterior cruciate ligament. Bone marrow stromal cells (BMSCs), ACL, and skin fibroblasts were seeded onto a resorbable suture material [poly(L-lactide/glycolide) multifilaments] at five different seeding densities, and cultured for up to 12 days. All cell types tested attached to the suture material, proliferated, and synthesized extracellular matrix rich in collagen type I. On day 12 the scaffolds seeded with BMSCs showed the highest DNA content (p engineered ligament.

  11. Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

    Science.gov (United States)

    Baris, Hagit N; Weisz Hubshman, Monika; Bar-Sever, Zvi; Kornreich, Liora; Shkalim Zemer, Vered; Cohen, Ian J

    2016-09-01

    Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Plasma-Activated Tropoelastin Functionalization of Zirconium for Improved Bone Cell Response

    Czech Academy of Sciences Publication Activity Database

    Yeo, G. C.; Santos, M.; Kondyurin, A.; Lišková, Jana; Weiss, A. S.; Bilek, M. M. M.

    2016-01-01

    Roč. 2, č. 4 (2016), s. 662-676 ISSN 2373-9878 R&D Projects: GA MZd(CZ) NV15-32497A; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : bone * plasma-activated coating * titanium * tropoelastin * zirconium Subject RIV: EI - Biotechnology ; Bionics Impact factor: 3.234, year: 2016

  13. Tenuigenin inhibits RANKL-induced osteoclastogenesis by down-regulating NF-κB activation and suppresses bone loss in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shuo [Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008 (China); Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012 (China); Li, Xianan [Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012 (China); Cheng, Liang [Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008 (China); Wu, Hongwei [Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012 (China); Zhang, Can [Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008 (China); Li, Kanghua, E-mail: lkh8738@sina.com [Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008 (China)

    2015-10-30

    Tenuigenin, a major active component of polygala tenuifolia root, has been used to treat patients with insomnia, dementia, and neurosis. In this study, we aimed to investigate the effects of tenuigenin on osteoclastogenesis and clarify the possible mechanism. We showed that tenuigenin inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption without cytotoxicity, which was further demonstrated by reduced osteoclast specific gene expression such as TRAP, c-Src, ATP6v0d2, etc. Moreover, the inhibitory effect of tenuigenin was associated with impaired NF-κB activity owing to delayed degradation/regeneration of IkBa and inhibition of p65 nuclear translocation. Consistent with the in vitro results, micro-ct scanning and analysis data showed that tenuigenin suppressed RANKL-induced bone loss in an animal model. Taken together, our data demonstrate that tenuigenin inhibit osteoclast formation and bone resorption both in vitro and in vivo, and comprise a potential therapeutic alternative for osteoclast-related disorders such as osteoporosis and cancer-induced bone destruction. - Highlights: • Tenuigenin suppresses osteoclasts formation, survival and function in vitro. • Tenuigenin impairs NF-κB activation. • Tenuigenin suppresses RANKL-induced bone lose in vivo. • Tenuigenin may be used for treating osteoclast related diseases.

  14. Tenuigenin inhibits RANKL-induced osteoclastogenesis by down-regulating NF-κB activation and suppresses bone loss in vivo

    International Nuclear Information System (INIS)

    Yang, Shuo; Li, Xianan; Cheng, Liang; Wu, Hongwei; Zhang, Can; Li, Kanghua

    2015-01-01

    Tenuigenin, a major active component of polygala tenuifolia root, has been used to treat patients with insomnia, dementia, and neurosis. In this study, we aimed to investigate the effects of tenuigenin on osteoclastogenesis and clarify the possible mechanism. We showed that tenuigenin inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption without cytotoxicity, which was further demonstrated by reduced osteoclast specific gene expression such as TRAP, c-Src, ATP6v0d2, etc. Moreover, the inhibitory effect of tenuigenin was associated with impaired NF-κB activity owing to delayed degradation/regeneration of IkBa and inhibition of p65 nuclear translocation. Consistent with the in vitro results, micro-ct scanning and analysis data showed that tenuigenin suppressed RANKL-induced bone loss in an animal model. Taken together, our data demonstrate that tenuigenin inhibit osteoclast formation and bone resorption both in vitro and in vivo, and comprise a potential therapeutic alternative for osteoclast-related disorders such as osteoporosis and cancer-induced bone destruction. - Highlights: • Tenuigenin suppresses osteoclasts formation, survival and function in vitro. • Tenuigenin impairs NF-κB activation. • Tenuigenin suppresses RANKL-induced bone lose in vivo. • Tenuigenin may be used for treating osteoclast related diseases.

  15. Mouse genome-wide association and systems genetics identify Asxl2 as a regulator of bone mineral density and osteoclastogenesis.

    Directory of Open Access Journals (Sweden)

    Charles R Farber

    2011-04-01

    Full Text Available Significant advances have been made in the discovery of genes affecting bone mineral density (BMD; however, our understanding of its genetic basis remains incomplete. In the current study, genome-wide association (GWA and co-expression network analysis were used in the recently described Hybrid Mouse Diversity Panel (HMDP to identify and functionally characterize novel BMD genes. In the HMDP, a GWA of total body, spinal, and femoral BMD revealed four significant associations (-log10P>5.39 affecting at least one BMD trait on chromosomes (Chrs. 7, 11, 12, and 17. The associations implicated a total of 163 genes with each association harboring between 14 and 112 genes. This list was reduced to 26 functional candidates by identifying those genes that were regulated by local eQTL in bone or harbored potentially functional non-synonymous (NS SNPs. This analysis revealed that the most significant BMD SNP on Chr. 12 was a NS SNP in the additional sex combs like-2 (Asxl2 gene that was predicted to be functional. The involvement of Asxl2 in the regulation of bone mass was confirmed by the observation that Asxl2 knockout mice had reduced BMD. To begin to unravel the mechanism through which Asxl2 influenced BMD, a gene co-expression network was created using cortical bone gene expression microarray data from the HMDP strains. Asxl2 was identified as a member of a co-expression module enriched for genes involved in the differentiation of myeloid cells. In bone, osteoclasts are bone-resorbing cells of myeloid origin, suggesting that Asxl2 may play a role in osteoclast differentiation. In agreement, the knockdown of Asxl2 in bone marrow macrophages impaired their ability to form osteoclasts. This study identifies a new regulator of BMD and osteoclastogenesis and highlights the power of GWA and systems genetics in the mouse for dissecting complex genetic traits.

  16. Multiple molecular forms of pyridinoline crosslinks generated by the ...

    African Journals Online (AJOL)

    molecular forms of pyridinoline crosslinks from insoluble bone type I collagen, and we studied ... resorbed in a dynamic process during ... proteins at 4 C for 24H in 4 mol/L .... fragments was merely due to interactions ... completely elucidated.

  17. [Bone remodeling and modeling/mini-modeling.

    Science.gov (United States)

    Hasegawa, Tomoka; Amizuka, Norio

    Modeling, adapting structures to loading by changing bone size and shapes, often takes place in bone of the fetal and developmental stages, while bone remodeling-replacement of old bone into new bone-is predominant in the adult stage. Modeling can be divided into macro-modeling(macroscopic modeling)and mini-modeling(microscopic modeling). In the cellular process of mini-modeling, unlike bone remodeling, bone lining cells, i.e., resting flattened osteoblasts covering bone surfaces will become active form of osteoblasts, and then, deposit new bone onto the old bone without mediating osteoclastic bone resorption. Among the drugs for osteoporotic treatment, eldecalcitol(a vitamin D3 analog)and teriparatide(human PTH[1-34])could show mini-modeling based bone formation. Histologically, mature, active form of osteoblasts are localized on the new bone induced by mini-modeling, however, only a few cell layer of preosteoblasts are formed over the newly-formed bone, and accordingly, few osteoclasts are present in the region of mini-modeling. In this review, histological characteristics of bone remodeling and modeling including mini-modeling will be introduced.

  18. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

    Science.gov (United States)

    Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  19. [Bone structure in rheumatoid arthritis].

    Science.gov (United States)

    Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

    2013-07-01

    In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

  20. Effect of PDGF-BB and beta-tricalcium phosphate (β-TCP) on bone formation around dental implants: a pilot study in sheep.

    Science.gov (United States)

    Choo, Tina; Marino, Victor; Bartold, P Mark

    2013-02-01

    The aim of this investigation was to examine the effect of a combination of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (β-TCP) on bone healing around dental implants with critical size circumferential defects. Three critical size circumferential defects were prepared in the ilium of six sheep. Three dental implants were placed into the centre of each defect and the 3.25 mm circumferential gap was filled with (a) blood clot alone; (b) β-TCP; (c) rhPDGF-BB (0.3 mg/ml) with β-TCP. All the defects in each group were covered with a Bio-Gide(®) resorbable barrier membrane. The sheep were sacrificed at 2 and 4 weeks and histological and histomorphometric analyses were performed to determine the percentage of new mineralized bone formation and residual β-TCP graft particles in the defects. Defects filled with rhPDGF-BB/β-TCP showed the highest rate of bone formation after 2 and 4 weeks with limited degradation of the β-TCP particles over 4 weeks. Defects filled with β-TCP showed the least bone fill after 2 and 4 weeks, and faster degradation of the β-TCP particles over 4 weeks compared with defects filled with rhPDGF-BB/β-TCP. Percentage of new mineralized bone was comparable in defects to blood clot alone and β-TCP after 4 weeks of healing, but there was a collapse in the defect area in defects with blood clot alone. In comparison, the space was maintained when β-TCP was used in defects at 4 weeks. Defects which had β-TCP alone showed an inhibition in bone healing at 2 and 4 weeks; however, the combination of rhPDGF-BB with β-TCP enhanced bone regeneration in these peri-implant bone defects at the same time intervals. © 2011 John Wiley & Sons A/S.

  1. 18F-FDG uptake in bone metastases

    International Nuclear Information System (INIS)

    Dineva, S.; Kostadinova, I.; Hadjidekov, V.

    2012-01-01

    Full text: Introduction: PET-CT is an established technique in staging cancer patients and monitoring the therapeutic response. In the literature it has been pointed out the different uptake in osteosclerotic and osteolytic metastases due to different metabolic activity. Objective: The aim of this study is to share authors initial experience in 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) evaluation of bone metastases secondary to breast cancer with different morphological appearance and to compare the diagnostic accuracy of CT and PET alone and in combination. Patients and methods: Fifty-nine (59) patients with bone lesions secondary to breast carcinoma are included in the retrospective study. The imaging protocol included a low-dose 16-raw detector CT scan with consequent PET scanning after the administration of 5 MBq/kg 18F-FDG activity. Bone metastases were characterized morphologically as being osteolytic, osteoblastic or mixed and metabolically as active, nonactive. Standard uptake value (SUV) of the most active metastatic lesion in each patient is measured. Results: Most patients had more than one type of bone metastases. 23 patients (38.98%) had osteolytic bone metastases, 32 (54.23%) had mixed, 14 (23.72%) had osteoblastic and 8 (13.55%) patients had metabolically active bone metastases without any morphological evidence. All of the osteolytic and all of the mixed bone lesions were metabolically active (100%). Amongst the osteoblastic bone metastases metabolic activity was seen in 11 (78.57%) patients and the rest 3 (21.42%) of them had only morphological evidence of bone lesions due to good therapeutic response. SUV varies from 3.2 to 18.5 (normal uptake threshold - 2.5). The aggressiveness of bone lesions is related to high metabolic activity and the lack of the latter is usually a sign of good therapeutic response. Metabolic activity without morphological changes is a feature of early bone marrow affection and

  2. Anterior cruciate ligament reconstruction using bone plug-free quadriceps tendon autograft: intermediate-term clinical outcome after 24-36 months.

    Science.gov (United States)

    Schulz, Arndt P; Lange, Vivien; Gille, Justus; Voigt, Christine; Fröhlich, Susanne; Stuhr, Markus; Jürgens, Christian

    2013-01-01

    Although known as a possible graft option for decades, quadriceps tendon grafts have often been termed a second-line graft option. We report a consecutive case series using this method as the primary treatment line. The rationale for this study was to evaluate the midterm results of this method in a prospective and consecutive case series. The primary study question was to determine the clinical results 24-36 months after primary anterior cruciate ligament (ACL) reconstruction using a bone plug-free quadriceps tendon autograft fixed with bioabsorbable cross-pins. The study population included 55 patients, of whom 24 were female (43.6%). The mean age at the index procedure was 31.7 years (15-58 years). All patients received an ACL construction using a bone block-free quadriceps tendon graft fixed with resorbable cross-pins. The postoperative regimen included partial weight-bearing for 3 weeks and flexion limited to 90° for six weeks; an orthosis was not used. The mean follow-up duration was 29.5 months (24.3-38.5 months) after the index procedure. The International Knee Documentation Committee (IKDC) subjective score and examination form was assessed, as well as the Lysholm and Gillquist score and the Tegner activity index. The Rolimeter arthrometer was used to assess the anterior laxity of the knee. Graft harvesting was possible in all cases; a bony extension was never required. On average, graft length was measured at 8.8 cm (7.5-10 cm). The mean IKDC subjective score at follow-up was 80.44 points (55.17-100 points, standard deviation [SD] 12.05). The mean preinjury Tegner activity index was 4.98 (2-7) compared to a mean value of 4.16 (2-7, SD 0.8) at follow-up. There was a mean loss of 0.82 index points. The average Lysholm and Gillquist score was 89 points (65-100, SD 17.7). Of the results, 89.1% were in the good or very good groups; in one case (1.8%), the result was poor, while the rest were fair. ACL reconstruction using a bone plug-free quadriceps tendon

  3. A novel image processing technique for 3D volumetric analysis of severely resorbed alveolar sockets with CBCT.

    Science.gov (United States)

    Manavella, Valeria; Romano, Federica; Garrone, Federica; Terzini, Mara; Bignardi, Cristina; Aimetti, Mario

    2017-06-01

    The aim of this study was to present and validate a novel procedure for the quantitative volumetric assessment of extraction sockets that combines cone-beam computed tomography (CBCT) and image processing techniques. The CBCT dataset of 9 severely resorbed extraction sockets was analyzed by means of two image processing software, Image J and Mimics, using manual and automated segmentation techniques. They were also applied on 5-mm spherical aluminum markers of known volume and on a polyvinyl chloride model of one alveolar socket scanned with Micro-CT to test the accuracy. Statistical differences in alveolar socket volume were found between the different methods of volumetric analysis (Psockets showed more accurate results, excellent inter-observer similarity and increased user friendliness. The clinical application of this method enables a three-dimensional evaluation of extraction socket healing after the reconstructive procedures and during the follow-up visits.

  4. Specific receptors for epidermal growth factor in human bone tumour cells and its effect on synthesis of prostaglandin E2 by cultured osteosarcoma cell line

    International Nuclear Information System (INIS)

    Hirata, Y.; Uchihashi, M.; Nakashima, H.; Fujita, T.; Matsukura, S.; Matsui, K.

    1984-01-01

    Using tumour cell lines derived from human bone tumours, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator in many tissues, and its effect on synthesis of prostaglandin (PG) E 2 , a potent bone-resorbing factor, by cultured osteosarcoma cell line were studied. Three tumour cell lines, one osteosarcoma (HOSO) and two giant cell tumours of the bone (G-1 and G-2), all possessed specific binding sites for 125 I-labelled EGF: the apparent dissociation constant was approximately 4-10 x 10 -10 M and the maximal binding capacity was 50 000-80 000 sites/cell. EGF had no mitogenic effect in these cell lines. However, these cell lines did not have specific binding sites for 125 I-labelled parathyroid hormone (PTH) or calcitonin. HOSO line produced and secreted PGE 2 into medium, while no significant amount of PGE 2 was demonstrated in G-1 or G-2 line. EGF significantly stimulated PGE 2 production in HOSO line in a dose-dependent manner (0.5-50 ng/ml); its stimulatory effect was completely abolished by indomethacin, an inhibitor of PG biosynthesis. Exogenous PGE 1 significantly stimulated cyclic AMP formation in HOSO line, whereas PGFsub(2α) PTH, calcitonin, or EGF had no effect. None of these calcium-regulating hormones affected cyclic AMP generation in either G-1 of G-2 line. These data indicate that human bone tumour cells have specific EGF receptors unrelated to cell growth, and suggest that EGF may be involved in bone resorption through a PGE 2 -mediated process in human osseous tissues. (author)

  5. Miscellaneous Burial Recovery in Eastern Washington, 1981.

    Science.gov (United States)

    1983-01-01

    jaws. Specifically, an abscess associated with the maxillary left first premolar was present. The maxillary alveolar structures also exhibited...completely resorbed — evidence of periodontal disease. The general condition of the teeth and the periodontal bone suggests an old individual who

  6. Pattern of uptake of americium-241 by the rat skeleton and its subsequent redistribution and retention: implications for human dosimetry and toxicology.

    Science.gov (United States)

    Priest, N D; Howells, G; Green, D; Haines, J W

    1983-01-01

    The distribution and retention of intravenously injected 241Am in the skeleton of the female rat has been investigated using autoradiographic and radiochemical techniques. The studies were designed to assess the dosimetric and toxicologic implications of an 241Am intake by man. They showed that in the rat approximately one third of the intravenously injected 241Am was deposited in the skeleton where it appeared to be retained with a long biological half-time. The studies also showed: 1 241Am is initially deposited onto all types of bone surface including endosteal surfaces, periosteal surfaces and those of the vascular canals within cortical bone, but seems to be preferentially deposited onto those that are resorbing, 2 Bone accretion results in the burial of surface deposits of 241Am, 3 Bone resorption causes the removal of 241Am from surfaces, 4 Resorbed 241Am is retained by phagocytic cells (probably macrophages) in the bone marrow, 5 The transfer of 241Am from the phagocytic cells in the marrow to adjacent bone surfaces seems to occur, (local recycling). 6 The possibility that some of the 241Am removed from the bone surfaces enters the blood and is redeposited in bone, (systemic recycling) cannot be dismissed. These results show that 241Am deposition and redistribution in bone shares many characteristics with other 'bone surface-seeking radionuclides' typified by 239Pu. Consequently, it is suggested that a similar model to that used to calculate annual limits of intake for 239Pu in man would be suitable for the calculation of corresponding values for the 241Am isotopes.

  7. 3D printed constructs with antibacterial or antitumor activity for surgical treatment of bone defects in cancer patients

    Science.gov (United States)

    Sergeeva, N. S.; Sviridova, I. K.; Komlev, V. S.; Karalkin, P. A.; Kirsanova, V. A.; Akhmedova, S. A.; Shanskij, Ya. D.; Kuvshinova, E. A.; Fedotov, A. Yu.; Teterina, A. Yu.; Barinov, S. M.

    2017-09-01

    The concept of functionalization with bioactive molecules and drugs is one of the most advanced areas of modern bone tissue biomaterial science in terms of enhancement of their osteoconductive and therapeutic properties. The purpose of this study was to develop the approaches for 3D printing of sodium alginate /gelatin /octacalcium phosphate-based constructs with antibacterial and antitumor activity intended for bone defects replacement in the patients with malignant diseases. In this work, we evaluated the drug release kinetic and physicochemical characteristics of the constructs, as well as their specific activity, biocompatibility and osteoplastic properties in in vitro and in vivo tests. The experimental results proved the principal possibility of creating the biocompatible bone substitutes with antibacterial/antitumor activity and maintaining osteoconductive properties by means of 3D printing method.

  8. Influence of short-term aluminum exposure on demineralized bone matrix induced bone formation

    Energy Technology Data Exchange (ETDEWEB)

    Severson, A.R. (Minnesota Univ., Duluth, MN (United States). Dept. of Anatomy and Cell Biology); Haut, C.F.; Firling, C.E. (Minnesota Univ., Duluth, MN (United States). Dept. of Biology); Huntley, T.E. (Minnesota Univ., Duluth, MN (United States). Dept. of Biochemistry and Molecular Biology)

    1992-12-01

    The effects of aluminum exposure on bone formation employing the demineralized bone matrix (DBM) induced bone development model were studied using 4-week-old Sprague-Dawley rats injected with a saline (control) or an aluminum chloride (experimental) solution. After 2 weeks of aluminum treatment, 20-mg portions of rat DBM were implanted subcutaneously on each side in the thoracic region of the control and experimental rats. Animals were killed 7, 12, or 21 days after implantation of the DBM and the developing plaques removed. No morphological, histochemical, or biochemical differences were apparent between plaques from day 7 control and experimental rats. Plaques from day 12 control and experimental rats exhibited cartilage formation and alkaline phosphatase activity localized in osteochondrogenic cells, chondrocytes, osteoblasts, and extracellular matrix. Unlike the plaques from control rats that contained many osteoblastic mineralizing fronts, the plaques from the 12-day experimental group had a preponderance of cartilaginous tissue, no evidence of mineralization, increased levels of alkaline phosphatase activity, and a reduced calcium content. Plaques developing for 21 days in control animals demonstrated extensive new bone formation and bone marrow development, while those in the experimental rats demonstrated unmineralized osteoid-like matrix with poorly developed bone marrow. Alkaline phosphatase activity of the plaques continued to remain high on day 21 for the control and experimental groups. Calcium levels were significantly reduced in the experimental group. These biochemical changes correlated with histochemical reductions in bone calcification. Thus, aluminum administration to rats appears to alter the differentiation and calcification of developing cartilage and bone in the DBM-induced bone formation model and suggests that aluminum by some mechanism alters the matrix calcification in growing bones. (orig.).

  9. Multielement analysis of iliac crest bone by neutron activation

    International Nuclear Information System (INIS)

    Aras, N.K.; Yilmaz, G.; Korkusuz, F.; Olmez, I.; Sepici, B.; Eksioglu, F.; Bode, P.

    2000-01-01

    Bone samples from iliac crest were obtained from apparently healthy female (n = 4) and male (n = 8) subjects with ages between 15-50. Cortical and trabecular parts were separated and soft tissues like fat, muscle and blood were removed. Calcium, Mg, Na, Cl, Fe, Zn, Br, Sr, and Cs were determined by instrumental neutron activation analysis and other techniques, and their relations were discussed. Fairly good agreement was obtained with literature data. These values may serve as reference values for subjects from a Turkish population. (author)

  10. The role of physical activity in bone health: a new hypothesis to reduce risk of vertebral fracture.

    Science.gov (United States)

    Sinaki, Mehrsheed

    2007-08-01

    Locomotion has always been a major criterion for human survival. Thus, it is no surprise that science supports the dependence of bone health on weight-bearing physical activities. The effect of physical activity on bone is site-specific. Determining how to perform osteogenic exercises, especially in individuals who have osteopenia or osteoporosis, without exceeding the biomechanical competence of bone always poses a dilemma and must occur under medical advice. This article presents the hypothesis that back exercises performed in a prone position, rather than a vertical position, may have a greater effect on decreasing the risk for vertebral fractures without resulting in compression fracture. The risk for vertebral fractures can be reduced through improvement in the horizontal trabecular connection of vertebral bodies.

  11. Palliation of bone cancer pain by antagonists of platelet-activating factor receptors.

    Directory of Open Access Journals (Sweden)

    Katsuya Morita

    Full Text Available Bone cancer pain is the most severe among cancer pain and is often resistant to current analgesics. Thus, the development of novel analgesics effective at treating bone cancer pain are desired. Platelet-activating factor (PAF receptor antagonists were recently demonstrated to have effective pain relieving effects on neuropathic pain in several animal models. The present study examined the pain relieving effect of PAF receptor antagonists on bone cancer pain using the femur bone cancer (FBC model in mice. Animals were injected with osteolytic NCTC2472 cells into the tibia, and subsequently the effects of PAF receptor antagonists on pain behaviors were evaluated. Chemical structurally different type of antagonists, TCV-309, BN 50739 and WEB 2086 ameliorated the allodynia and improved pain behaviors such as guarding behavior and limb-use abnormalities in FBC model mice. The pain relieving effects of these antagonists were achieved with low doses and were long lasting. Blockade of spinal PAF receptors by intrathecal injection of TCV-309 and WEB 2086 or knockdown of the expression of spinal PAF receptor protein by intrathecal transfer of PAF receptor siRNA also produced a pain relieving effect. The amount of an inducible PAF synthesis enzyme, lysophosphatidylcholine acyltransferase 2 (LPCAT2 protein significantly increased in the spinal cord after transplantation of NCTC 2472 tumor cells into mouse tibia. The combination of morphine with PAF receptor antagonists develops marked enhancement of the analgesic effect against bone cancer pain without affecting morphine-induced constipation. Repeated administration of TCV-309 suppressed the appearance of pain behaviors and prolonged survival of FBC mice. The present results suggest that PAF receptor antagonists in combination with, or without, opioids may represent a new strategy for the treatment of persistent bone cancer pain and improve the quality of life of patients.

  12. Work- and travel-related physical activity and alcohol consumption: relationship with bone mineral density and calcaneal quantitative ultrasonometry.

    Science.gov (United States)

    Sritara, Chanika; Thakkinstian, Ammarin; Ongphiphadhanakul, Boonsong; Pornsuriyasak, Prapaporn; Warodomwichit, Daruneewan; Akrawichien, Tawatchai; Vathesatogkit, Prin; Sritara, Piyamitr

    2015-01-01

    A number of healthy workers rarely exercise because of a lack of time or resources. Physical activity related to work and everyday travel may be more feasible, but evidence of its beneficial effect on bone health is scarce. We assessed if this form of physical activity was associated with higher bone mineral density (BMD) and stiffness index (SI) when adjusted for recreational physical activity, age, body mass index, smoking, alcohol consumption, education, and serum level of 25-hydroxyvitamin D. Healthy workers, aged 25-54 yr, of the Electricity Generating Authority of Thailand were surveyed. The outcomes were BMD (lumbar spine, femoral neck, and total hip) and calcaneal SI. Physical activity was estimated using the global physical activity questionnaire and considered active when >600 metabolic equivalent tasks (min). Of 2268 subjects, 74% were men. Active male subjects had significantly higher BMD at the femoral neck and total hip (pwomen (p>0.05). In men, work and travel physical activity seems beneficial to male bone health; hence, it should be encouraged. Furthermore, smoking appeared harmful while moderate alcohol consumption was beneficial. Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  13. Detection of active alveolar bone destruction in human periodontal disease by analysis of radiopharmaceutical uptake after a single injection of 99m-Tc-methylene diphosphonate

    International Nuclear Information System (INIS)

    Jeffcoat, M.K.; Williams, R.C.; Holman, B.L.; English, R.; Goldhaber, P.

    1986-01-01

    Previous studies have shown that, following a single injection of 99m-Tc-MDP, measurement of bone-seeking radiopharmaceutical uptake can detect ''active'' alveolar bone loss due to periodontal disease in beagle dogs, as determined by radiographs taken at the time of, and several months after, the nuclear medicine procedure. The efficacy of this diagnostic test, however, had not been assessed in human periodontal disease. The ability of a single boneseeking radiopharmaceutical uptake examination to detect ''active'' alveolar bone loss due to periodontal disease in human patients was assessed by comparing a single uptake measurement to the rate of bone loss determined from serial radiographs taken over a 6-month period. Uptake was expressed as a ratio of the cpm from the alveolar bone divided by the cpm from the non-tooth supporting bone of the nuchal crest. High uptake ratios were associated with ''active'' loss and low uptake ratios were associated with little if any change in alveolar bone height (p<0.001). The nuclear medicine examination was an accurate detector of periodontal disease activity in nearly 80% of the individual teeth studied. These data indicate that high bone-seeking radiopharmaceutical uptake ratios may be pathognomonic of active bone loss in human periodontal disease. (author)

  14. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

    Directory of Open Access Journals (Sweden)

    Rinaldo Florencio-Silva

    2015-01-01

    Full Text Available Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines and systemic (e.g., calcitonin and estrogens factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  15. A study of 23 unicameral bone cysts of the calcaneus: open chip allogeneic bone graft versus percutaneous injection of bone powder with autogenous bone marrow.

    Science.gov (United States)

    Park, Il-Hyung; Micic, Ivan Dragoljub; Jeon, In-Ho

    2008-02-01

    The treatment of unicameral bone cyst varies from percutaneous needle biopsy, aspiration and local injection of steroid, autologous bone marrow, or demineralized bone matrix to curettage and open bone-grafting. The purpose of this study was to compare the results of open chip allogeneic bone graft versus percutaneous injection of demineralized bone powder with autogenous bone marrow in management of calcaneal cysts. Twenty-three calcaneal unicameral cysts in 20 patients were treated. Lyophilized irradiated chip allogeneic bone (CAB) and autogenous bone marrow were used for treatment of 13 cysts in 11 patients, and 10 cysts in 9 patients were treated with percutaneous injection of irradiated allogeneic demineralized bone powder (DBP) and autogenous bone marrow. There were 11 males and 9 female patients with mean age of 17 years. The patients were followed for an average of 49.4 months. Complete healing was achieved in 9 cysts treated with chip allogeneic bone and in 5 cysts treated with powdered bone. Four cysts treated with CAB and 3 cysts treated with DBP healed with a defect. Two cysts treated with powdered bone and autogenous bone marrow were classified as persistent. No infections or pathological fractures were observed during the followup period. Percutaneous injection of a mixture of allogeneic bone powder with autogenous bone marrow is a minimal invasive method and could be an effective alternative in the treatment of unicameral calcaneal bone cysts. The postoperative morbidity was low, the hospital stay was brief, and patient's comfort for unrestricted activity was enhanced.

  16. Multifocal bone and bone marrow lesions in children - MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Raissaki, Maria; Demetriou, Stelios; Spanakis, Konstantinos; Skiadas, Christos; Karantanas, Apostolos H. [University of Crete, Faculty of Medicine, Department of Radiology, University Hospital of Heraklion, Heraklion, Crete (Greece); Katzilakis, Nikolaos; Stiakaki, Eftichia [University of Crete, Faculty of Medicine, Department of Pediatric Hematology-Oncology, University Hospital of Heraklion, Heraklion, Crete (Greece); Velivassakis, Emmanouil G. [University Hospital of Heraklion, Orthopedic Clinic, Heraklion, Crete (Greece)

    2017-03-15

    Polyostotic bone and bone marrow lesions in children may be due to various disorders. Radiographically, lytic lesions may become apparent after loss of more than 50% of the bone mineral content. Scintigraphy requires osteoblastic activity and is not specific. MRI may significantly contribute to the correct diagnosis and management. Accurate interpretation of MRI examinations requires understanding of the normal conversion pattern of bone marrow in childhood and of the appearances of red marrow rests and hyperplasia. Differential diagnosis is wide: Malignancies include metastases, multifocal primary sarcomas and hematological diseases. Benign entities include benign tumors and tumor-like lesions, histiocytosis, infectious and inflammatory diseases, multiple stress fractures/reactions and bone infarcts/ischemia. (orig.)

  17. Stress fractures and bone pain

    International Nuclear Information System (INIS)

    Groshar, D.; Even-Sapir, E.; Lam, M.; Israel, O.; Front, D.

    1984-01-01

    Stress fractures result from an unusual repetitive physical activity causing absorption of bone in excess of repair and bone formation. This leads to the weakening of the bone and subsequently to a fracture. It is a benign condition that if recognized in time does not need any treatment besides rest. However, if diagnosis is not made and physical activity continues it may result in severe injury to the bone and a frank fracture may result. Pain is the typical clinical feature and bone scintigraphy, being more sensitive than radiography, is done to establish early diagnosis. The presence of asymptomatic sites of abnormal bone uptake typical of stress fracture in which pain appeared only about 2 weeks after scintigraphy, drew the authors' attention to the question of how close is the relationship between stress fractures and bone pain. Sixty-four military recruits diagnosed as suffering from stress fracture were investigated in order to correlate sites with abnormal uptake of Tc-99m MDP on bone scintigraphy with sites of local pain. In 37 (58%) subjects multiple sites of abnormal uptake were recognised. Of 123 sites of abnormal uptake, 31 (25%) were asymptomatic. In three patients bone pain appeared at the site of the abnormal uptake two weeks after scintigraphy. Bone scintigraphy appears to be more sensitive than bone pain in the diagnosis of stress fractures. The osteoblastic activity which manifests itself by abnormal uptake appears in some cases earlier than the pain caused by the fracture. Present findings may suggest that under certain circumstances, in a population prone to stress fracture, bone scan should be considered as a screening method

  18. Bioactive glass-ceramic bone repair associated or not with autogenous bone: a study of organic bone matrix organization in a rabbit critical-sized calvarial model.

    Science.gov (United States)

    Biguetti, Claudia Cristina; Cavalla, Franco; Tim, Carla Roberta; Saraiva, Patrícia Pinto; Orcini, Wilson; De Andrade Holgado, Leandro; Rennó, Ana Claudia Muniz; Matsumoto, Mariza Akemi

    2018-04-26

    The aim of the study was to analyze bone matrix (BMX) organization after bone grafting and repair using a new bioactive glass-ceramic (Biosilicate ® ) associated or not with particulate autogenous bone graft. Thirty rabbits underwent surgical bilateral parietal defects and divided into groups according to the materials used: (C) control-blood clot, (BG) particulate autogenous bone, (BS) bioactive glass-ceramic, and BG + BS. After 7, 14, and 30 days post-surgery, a fragment of each specimen was fixed in - 80 °C liquid nitrogen for zymographic evaluation, while the remaining was fixed in 10% formalin for histological birefringence analysis. The results of this study demonstrated that matrix organization in experimental groups was significantly improved compared to C considering collagenous organization. Zymographic analysis revealed pro-MMP-2, pro-MMP-9, and active (a)-MMP-2 in all groups, showing gradual decrease of total gelatinolytic activity during the periods. At day 7, BG presented more prominent gelatinolytic activity for pro-MMP-2 and 9 and a-MMP-2, when compared to the other groups. In addition, at day 7, a 53% activation ratio (active form/[active form + latent form]) was evident in C group, 33% in BS group, and 31% in BG group. In general, BS allowed the production of a BMX similar to BG, with organized collagen deposition and MMP-2 and MMP-9 disponibility, permitting satisfactory bone remodeling at the late period. The evaluation of new bone substitute, with favorable biological properties, opens the possibility for its use as a viable and efficient alternative to autologous bone graft.

  19. Patterns of bone-marrow scintigraphy

    International Nuclear Information System (INIS)

    Touya, J.J.; Lee, G.S.; Narvaez, M.; Marciano, D.

    1977-01-01

    111 In-transferrin, radiocolloid and bone scans were performed within one week on 105 from more than 250 scanned patients with different haematological disorders. All patients had complete haematological workups and confirmed final diagnoses. From the comparison of the 111 In-transferrin marrow scan with the radiocolloid marrow scan and bone scan, eight basic patterns of localized or generalized disorders in the bone marrow cell production were delineated. The first pattern was called a cold area and two sub-patterns were distinguished in it. A cold area in the erythropoietic and reticuloendothelial scans associated with cold or normal areas in the bone scan corresponded to radiation damage of the marrow or multiple myeloma; a cold area in both marrow scans with a hot area in the bone scan to tumour, infarct and bone trauma. The second pattern was called a hot area. A hot area in the two marrow scans with a normal bone scan was observed in islands of active bone-marrow. Hot areas in both 111 In-transferrin and bone scan associated with a cold area in the radiocolloid scan were observed in tumours growing in bones with or without little active bone marrow. Hot areas on the three scans were observed in osteomyelitis of bones of the extremities. The third pattern was bone-marrow expansion, which was observed in hereditary haemolytic anaemias, in myeloproliferative disorders and in patients with bone-marrow damage following irradiation. The fourth pattern was saturation of the serum iron-binding capacity and it was manifested by increased activity in the kidneys in the 111 In-transferrin scan. The fifth pattern was bone-marrow failure which consists of decreased accumulation in the marrow and increased accumulation in the liver of marrow-seeking agents associated with normal bone scan. The sixth pattern, pure red cell aplasia, was characterized by less accumulation of 111 In-transferrin than radiocolloid in the bone marrow. The seventh pattern, bone-marrow siderosis

  20. Chemical Makeup of Microdamaged Bone Differs from Undamaged Bone

    International Nuclear Information System (INIS)

    Ruppel, M.; Burr, D.; Miller, L.

    2006-01-01

    Microdamage naturally occurs in bone tissue as a result of cyclic loading placed on the body from normal daily activities. While it is usually repaired through the bone turnover process, accumulation of microdamage may result in reduced bone quality and increased fracture risk. It is unclear whether certain areas of bone are more susceptible to microdamage than others due to compositional differences. This study examines whether areas of microdamaged bone are chemically different than undamaged areas of bone. Bone samples (L3 vertebrae) were harvested from 15 dogs. Samples were stained with basic fuchsin, embedded in poly-methylmethacrylate, and cut into 5-(micro)m-thick sections. Fuchsin staining was used to identify regions of microdamage, and synchrotron infrared microspectroscopic imaging was used to determine the local bone composition. Results showed that microdamaged areas of bone were chemically different than the surrounding undamaged areas. Specifically, the mineral stoichiometry was altered in microdamaged bone, where the carbonate/protein ratio and carbonate/phosphate ratio were significantly lower in areas of microdamage, and the acid phosphate content was higher. No differences were observed in tissue mineralization (phosphate/protein ratio) or crystallinity between the microdamaged and undamaged bone, indicating that the microdamaged regions of bone were not over-mineralized. The collagen cross-linking structure was also significantly different in microdamaged areas of bone, consistent with ruptured cross-links and reduced fracture resistance. All differences in composition had well-defined boundaries in the microcrack region, strongly suggesting that they occurred after microcrack formation. Even so, because microdamage results in an altered bone composition, an accumulation of microdamage might result in a long-term reduction in bone quality

  1. Validation of a physical activity questionnaire to measure the effect of mechanical strain on bone mass.

    Science.gov (United States)

    Kemper, Han C G; Bakker, I; Twisk, J W R; van Mechelen, W

    2002-05-01

    Most of the questionnaires available to estimate the daily physical activity levels of humans are based on measuring the intensity of these activities as multiples of resting metabolic rate (METs). Metabolic intensity of physical activities is the most important component for evaluating effects on cardiopulmonary fitness. However, animal studies have indicated that for effects on bone mass the intensity in terms of energy expenditure (metabolic component) of physical activities is less important than the intensity of mechanical strain in terms of the forces by the skeletal muscles and/or the ground reaction forces. The physical activity questionnaire (PAQ) used in the Amsterdam Growth and Health Longitudinal Study (AGAHLS) was applied to investigate the long-term effects of habitual physical activity patterns during youth on health and fitness in later adulthood. The PAQ estimates both the metabolic components of physical activities (METPA) and the mechanical components of physical activities (MECHPA). Longitudinal measurements of METPA and MECHPA were made in a young population of males and females ranging in age from 13 to 32 years. This enabled evaluation of the differential effects of physical activities during adolescence (13-16 years), young adulthood (21-28 years), and the total period of 15 years (age 13-28 years) on bone mineral density (BMD) of the lumbar spine, as measured by dual-energy X-ray absorptiometry (DXA) in males (n = 139) and females (n = 163) at a mean age of 32 years. The PAQ used in the AGAHLS during adolescence (13-16 years) and young adulthood (21-28 years) has the ability to measure the physical activity patterns of both genders, which are important for the development of bone mass at the adult age. MECHPA is more important than METPA. The highest coefficient of 0.33 (p PAQ was established by comparing PAQ scores during four annual measurements in 200 boys and girls with two other objective measures of physical activity: movement

  2. Activity of bone morphogenetic protein-7 after treatment at various temperatures: freezing vs. pasteurization vs. allograft.

    Science.gov (United States)

    Takata, Munetomo; Sugimoto, Naotoshi; Yamamoto, Norio; Shirai, Toshiharu; Hayashi, Katsuhiro; Nishida, Hideji; Tanzawa, Yoshikazu; Kimura, Hiroaki; Miwa, Shinji; Takeuchi, Akihiko; Tsuchiya, Hiroyuki

    2011-12-01

    Insufficient bone union is the occasional complication of biomechanical reconstruction after malignant bone tumor resection using temperature treated tumor bearing bone; freezing, pasteurization, and autoclaving. Since bone morphogenetic protein (BMP) plays an important role in bone formation, we assessed the amount and activity of BMP preserved after several temperature treatments, including -196 and -73°C for 20 min, 60 and 100°C for 30 min, 60°C for 10h following -80°C for 12h as an allograft model, and 4°C as the control. The material extracted from the human femoral bone was treated, and the amount of BMP-7 was analyzed using an enzyme-linked immunosorbent assay. Then, the activity of recombinant human BMP-7 after the treatment was assessed using a bioassay with NIH3T3 cells and immunoblotting analysis to measure the amount of phospho-Smad, one of the signaling substrates that reflect the intracellular reaction of BMPs. Both experiments revealed that BMP-7 was significantly better preserved in the hypothermia groups. The percentages of the amount of BMP-7 in which the control group was set at 100% were 114%, 108%, 70%, 49%, and 53% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. The percentages of the amount of phospho-Smad were 89%, 87%, 24%, 4.9%, and 14% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. These results suggested that freezing possibly preserves osteoinductive ability than hyperthermia treatment. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Histologic diagnosis of metabolic bone diseases: bone histomorphometry

    Directory of Open Access Journals (Sweden)

    L. Dalle Carbonare

    2011-09-01

    Full Text Available Histomorphometry or quantitative histology is the analysis on histologic sections of bone resorption parameters, formation and structure. It is the only technique that allows a dynamic evaluation of the activity of bone modelling after labelling with tetracycline. Moreover, the new measurement procedures through the use of the computer allow an assessment of bone microarchitecture too. Histomorphometric bone biopsy is a reliable and well-tolerated procedure. Complications are reported only in 1% of the subjects (hematoma, pain, transient neuralgia. Histomorphometry is used to exclude or confirm the diagnosis of osteomalacia. It is employed in the evaluation of bone damage associated with particular treatments (for example, anticonvulsants or in case of rare bone diseases (osteogenesis imperfecta, systemic mastocytosis. It is also an essential approach when clinical, biochemical and other diagnostic data are not consistent. Finally, it is a useful method to understand the pathophysiologic mechanisms of drugs. The bone sample is taken at the level of iliac crest under local anesthesia. It is then put into methyl-metacrilate resin where the sections are prepared for the microscopic analysis of the various histomorphometric parameters.

  4. Inhibition of heterotopic osteogenesis in rats by a new bioerodible system for local delivery of indomethacin

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G

    1992-01-01

    A study was done to evaluate the effect of a system for the local delivery of indomethacin on demineralized bone-induced formation of heterotopic bone in the abdominal muscles of rats. Two separate investigations were conducted on a total of forty-eight Wistar rats. In both series, two types of i...... of bone, as demonstrated by light microscopy and by uptake of 85Sr. The polyorthoester, with or without the drug, caused little tissue reaction and was resorbed almost completely at four weeks....

  5. Radiotherapy Suppresses Bone Cancer Pain through Inhibiting Activation of cAMP Signaling in Rat Dorsal Root Ganglion and Spinal Cord

    Directory of Open Access Journals (Sweden)

    Guiqin Zhu

    2016-01-01

    Full Text Available Radiotherapy is one of the major clinical approaches for treatment of bone cancer pain. Activation of cAMP-PKA signaling pathway plays important roles in bone cancer pain. Here, we examined the effects of radiotherapy on bone cancer pain and accompanying abnormal activation of cAMP-PKA signaling. Female Sprague-Dawley rats were used and received tumor cell implantation (TCI in rat tibia (TCI cancer pain model. Some of the rats that previously received TCI treatment were treated with X-ray radiation (radiotherapy. Thermal hyperalgesia and mechanical allodynia were measured and used for evaluating level of pain caused by TCI treatment. PKA mRNA expression in dorsal root ganglion (DRG was detected by RT-PCR. Concentrations of cAMP, IL-1β, and TNF-α as well as PKA activity in DRG and the spinal cord were measured by ELISA. The results showed that radiotherapy significantly suppressed TCI-induced thermal hyperalgesia and mechanical allodynia. The level of PKA mRNA in DRG, cAMP concentration and PKA activity in DRG and in the spinal cord, and concentrations of IL-1β and TNF-α in the spinal cord were significantly reduced by radiotherapy. In addition, radiotherapy also reduced TCI-induced bone loss. These findings suggest that radiotherapy may suppress bone cancer pain through inhibition of activation of cAMP-PKA signaling pathway in DRG and the spinal cord.

  6. Heterotopic new bone formation causes resorption of the inductive bone matrix

    International Nuclear Information System (INIS)

    Nilsson, O.S.; Persson, P.E.; Ekelund, A.

    1990-01-01

    The bone matrix of growing rats was labeled by multiple injections of 3H-proline, and demineralized bone matrix (DBM) was prepared. The DBM was allotransplanted heterotopically into growing rats. New bone formation was induced in and around the implants. The new bone formation was accompanied by a decrease in the content of 3H; 20 and 30 days after implantation, 72% and 46%, respectively, of the activity remained in the implants. Daily injections of indomethacin (2 mg/kg) inhibited calcium uptake by about 20% at 20 and 30 days and inhibited the release of 3H from the DBM to a similar degree. Heterotopic bone induction by DBM is accompanied by matrix resorption, and inhibition of the new bone formation decreases the resorption of DBM

  7. Activity of Fosfomycin- and Daptomycin-Containing Bone Cement on Selected Bacterial Species Being Associated with Orthopedic Infections

    Directory of Open Access Journals (Sweden)

    Sigrun Eick

    2017-01-01

    Full Text Available The purpose of this study was to determine activity of fosfomycin/gentamicin and daptomycin/gentamicin-containing PMMA bone-cement against Staphylococcus aureus (MRSA, MSSA, Staphylococcus epidermidis, Enterococcus faecium (VRE, and E. coli (ESBL; only fosfomycin. Test specimens of the bone cement were formed and bacteria in two concentrations were added one time or repeatedly up to 96 h. All fosfomycin-containing cement killed ultimately all MSSA, Staphylococcus epidermidis, and E. coli within 24 h; growth of MRSA was suppressed up to 48 h. Activity of daptomycin-containing cement depended on the concentration; the highest concentrated bone cement used (1.5 g daptomycin/40 g of powder was active against all one-time added bacteria. When bacteria were added repeatedly to fosfomycin-containing cement, growth was suppressed up to 96 h and that of MRSA and VRE only up to 24 h. The highest concentration of daptomycin suppressed the growth of repeated added bacteria up to 48 h (VRE until 96 h (MSSA, MRSA. In conclusion, PMMA bone cement with 1.5 g of daptomycin and 0.5 g of gentamicin may be an alternative in treatment of periprosthetic infections caused by Gram-positive bacteria.

  8. Proteinase activated receptor 1 mediated fibrosis in a mouse model of liver injury: a role for bone marrow derived macrophages.

    Directory of Open Access Journals (Sweden)

    Yiannis N Kallis

    Full Text Available Liver fibrosis results from the co-ordinated actions of myofibroblasts and macrophages, a proportion of which are of bone marrow origin. The functional effect of such bone marrow-derived cells on liver fibrosis is unclear. We examine whether changing bone marrow genotype can down-regulate the liver's fibrotic response to injury and investigate mechanisms involved. Proteinase activated receptor 1 (PAR1 is up-regulated in fibrotic liver disease in humans, and deficiency of PAR1 is associated with reduced liver fibrosis in rodent models. In this study, recipient mice received bone marrow transplantation from PAR1-deficient or wild-type donors prior to carbon tetrachloride-induced liver fibrosis. Bone marrow transplantation alone from PAR1-deficient mice was able to confer significant reductions in hepatic collagen content and activated myofibroblast expansion on wild-type recipients. This effect was associated with a decrease in hepatic scar-associated macrophages and a reduction in macrophage recruitment from the bone marrow. In vitro, PAR1 signalling on bone marrow-derived macrophages directly induced their chemotaxis but did not stimulate proliferation. These data suggest that the bone marrow can modulate the fibrotic response of the liver to recurrent injury. PAR1 signalling can contribute to this response by mechanisms that include the regulation of macrophage recruitment.

  9. Detection of active alveolar bone destruction in human periodontal disease by analysis of radiopharmaceutical uptake after a single injection of 99m-Tc-methylene diphosphonate

    Energy Technology Data Exchange (ETDEWEB)

    Jeffcoat, M.K.; Williams, R.C.; Holman, B.L.; English, R.; Goldhaber, P.

    1986-01-01

    Previous studies have shown that, following a single injection of 99m-Tc-MDP, measurement of bone-seeking radiopharmaceutical uptake can detect ''active'' alveolar bone loss due to periodontal disease in beagle dogs, as determined by radiographs taken at the time of, and several months after, the nuclear medicine procedure. The efficacy of this diagnostic test, however, had not been assessed in human periodontal disease. The ability of a single boneseeking radiopharmaceutical uptake examination to detect ''active'' alveolar bone loss due to periodontal disease in human patients was assessed by comparing a single uptake measurement to the rate of bone loss determined from serial radiographs taken over a 6-month period. Uptake was expressed as a ratio of the cpm from the alveolar bone divided by the cpm from the non-tooth supporting bone of the nuchal crest. High uptake ratios were associated with ''active'' loss and low uptake ratios were associated with little if any change in alveolar bone height (p<0.001). The nuclear medicine examination was an accurate detector of periodontal disease activity in nearly 80% of the individual teeth studied. These data indicate that high bone-seeking radiopharmaceutical uptake ratios may be pathognomonic of active bone loss in human periodontal disease.

  10. TCP is hardly resorbed and not osteoconductive in a non-loading calvarial model.

    Science.gov (United States)

    Handschel, Jörg; Wiesmann, Hans Peter; Stratmann, Udo; Kleinheinz, Johannes; Meyer, Ulrich; Joos, Ulrich

    2002-04-01

    Tricalciumphosphate (TCP) has been used as a ceramic bone substitute material in the orthopedic field as well as in craniofacial surgery. Some controversies exist concerning the osteoconductive potential of this material in different implantation sites. This study was designed to evaluate the biological response of calvarial bone towards TCP granules under non-loading conditions to assess the potential of TCP as a biodegredable and osteoconductive bone substitue material for the cranial vault. Full-thickness non-critical size defects were made bilaterally in the calvaria of 21 adult Wistar rats. One side was filled by TCP granules, the contralateral side was left empty and used as a control. Animals were sacrified in defined time intervals up to 6 months. Bone regeneration was analyzed with special respect toward the micromorphological and microanalytical features of the material-bone interaction by electron microscopy and electron diffraction analysis. Histologic examination revealed no TCP degradation even after 6 months of implantation. In contrast, a nearly complete bone regeneration of control defects was found after 6 months. At all times TCP was surrounded by a thin fibrous layer without presence of osteoblasts and features of regular mineralization. As far as degradation and substitution are concerned, TCP is a less favourable material tinder conditions of non-loading.

  11. BMI-1 Mediates Estrogen-Deficiency-Induced Bone Loss by Inhibiting Reactive Oxygen Species Accumulation and T Cell Activation.

    Science.gov (United States)

    Li, Jinbo; Wang, Qian; Yang, Renlei; Zhang, Jiaqi; Li, Xing; Zhou, Xichao; Miao, Dengshun

    2017-05-01

    Previous studies have shown that estrogen regulates bone homeostasis through regulatory effects on oxidative stress. However, it is unclear how estrogen deficiency triggers reactive oxygen species (ROS) accumulation. Recent studies provide evidence that the B lymphoma Mo-MLV insertion region 1 (BMI-1) plays a critical role in protection against oxidative stress and that this gene is directly regulated by estrogen via estrogen receptor (ER) at the transcriptional level. In this study, ovariectomized mice were given drinking water with/without antioxidant N-acetyl-cysteine (NAC, 1 mg/mL) supplementation, and compared with each other and with sham mice. Results showed that ovariectomy resulted in bone loss with increased osteoclast surface, increased ROS levels, T cell activation, and increased TNF and RANKL levels in serum and in CD4 T cells; NAC supplementation largely prevented these alterations. BMI-1 expression levels were dramatically downregulated in CD4 T cells from ovariectomized mice. We supplemented drinking water to BMI-1-deficient mice with/without NAC and compared them with each other and with wild-type (WT) mice. We found that BMI-1 deficiency mimicked alterations observed in ovariectomy whereas NAC supplementation reversed all alterations induced by BMI-1 deficiency. Because T cells are critical in mediating ovariectomy-induced bone loss, we further assessed whether BMI-1 overexpression in lymphocytes can protect against estrogen deficiency-induced osteoclastogenesis and bone loss by inhibiting oxidative stress, T cell activation, and RANKL production. When WT and Eμ-BMI-1 transgenic mice with BMI-1 specifically overexpressed in lymphocytes were ovariectomized and compared with each other and with WT sham mice, we found that BMI-1 overexpression in lymphocytes clearly reversed all alterations induced by ovariectomy. Results from this study indicate that estrogen deficiency downregulates BMI-1 and subsequently increases ROS, T cell activation, and

  12. Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation

    DEFF Research Database (Denmark)

    Justesen, Jeannette; Mosekilde, Lis; Holmes, Megan

    2004-01-01

    Glucocorticoids (GCs) exert potent, but poorly characterized, effects on the skeleton. The cellular activity of GCs is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). The type 1 isoform, which predominates in bone, functions as a reductase in intact cells...... and regenerates active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of the present study was to investigate the role of this intracrine activation of GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/-)). The HSD1(-/-) mice exhibited no significant changes...... in cortical or trabecular bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age-related bone loss similar to that observed in Wt mice. Histomorphometric analysis showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt mice. However, examination of bone marrow...

  13. Bone microarchitecture and bone mineral density in multiple sclerosis

    DEFF Research Database (Denmark)

    Olsson, A; Oturai, A B; Søndergaard, H B

    2018-01-01

    BACKGROUND: Multiple sclerosis (MS) patients are at increased risk of reduced bone mineral density (BMD) and fractures. The aetiology of bone loss in MS is unclear. Trabecular bone score (TBS) is a novel analytical tool that provides a measurement of the bone microarchitecture. Decreased TBS...... included. TBS was calculated using TBS iNsight software (MediMaps® ). Multivariable regression analyses were performed with information on smoking, alcohol, glucocorticoid (GC) treatment, sun exposure, physical activity, vitamin D and BMI. RESULTS: Trabecular bone score was not significantly different from...... an age-matched reference population. Low TBS was associated with high age (P = .014) and smoking (P = .03). Smoking and physical inactivity were associated with low BMD in spine (P = .034, P = .032). GC treatment was not associated with TBS. CONCLUSION: We could not find altered TBS values among MS...

  14. Reconstruction of the mandible bone by treatment of resected bone with pasteurization.

    Science.gov (United States)

    Uehara, Masataka; Inokuchi, Tsugio; Sano, Kazuo; Sumita, Yoshinori; Tominaga, Kazuhiro; Asahina, Izumi

    2012-11-01

    The results of long-term follow-up for reimplantation of the mandibular bone treated with pasteurization are reported. Mandibulectomy was performed for mandibular malignancy in 3 cases. The resected bones were subsequently reimplanted after treatment with pasteurization in 3 cases to eradicate tumor cells involved in the resected bone. Although postoperative infection was observed in 2 of 3 cases, reimplantation of the resected mandibular bone treated by pasteurization was finally successful. Ten to 22 years of follow-up was carried out. Pasteurization was able to devitalize tumor cells involved in the resected bone and to preserve bone-inductive activity. Reimplantation of pasteurization could be a useful strategy for reconstruction of the mandible in patients with mandibular malignancy.

  15. Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation

    Science.gov (United States)

    Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

    2016-01-01

    Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclastspecific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β–induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss. PMID:26108893

  16. Water Extract of Deer Bones Activates Macrophages and Alleviates Neutropenia

    Directory of Open Access Journals (Sweden)

    Han-Seok Choi

    2013-01-01

    Full Text Available Extracts from deer bones, called nok-gol in Korean, have long been used to invigorate Qi. While neutropenia is not well detected in normal physiological condition, it could be a cause of severe problems to develop diseases such as infectious and cancerous diseases. Thus, a prevention of neutropenia in normal physiology and pathophysiological states is important for maintaining Qi and preventing disease progress. In cell biological aspects, activated macrophages are known to prevent neutropenia. In this study, we demonstrate that water extract of deer bone (herein, NG prevents neutropenia by activating macrophages. In mouse neutropenia model system in vivo where ICR mice were treated with cyclophosphamide to immunosuppress, an oral administration of NG altered the number of blood cells including lymphocytes, neutrophils, basophils, and eosinophils. This in vivo effect of NG was relevant to that of granulocyte colony stimulating factor (G-CSF that was known to improve neutropenia. Our in vitro studies further showed that NG treatment increased intracellular reactive oxygen species (ROS and promoted macrophagic differentiation of mouse monocytic Raw264.7 cells in a dose-dependent manner. In addition, NG enhanced nitric oxide (NO synthesis and secretions of cytokines including IL-6 and TNF-α. Consistently, NG treatment induced phosphorylation of ERK, JNK, IKK, IκBα, and NF-κB in Raw264.7 cells. Thus, our data suggest that NG is helpful for alleviating neutropenia.

  17. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo.

    Science.gov (United States)

    He, Shengwei; Zhao, Wenzhi; Zhang, Lu; Mi, Lidong; Du, Guangyu; Sun, Chuanxiu; Sun, Xuegang

    2017-01-01

    To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo . Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz) were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligan, and pre-collagen type 1 α were measured. Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligand, and pre-collagen type 1 α were also markedly higher following 25 and 50 Hz treatment. Low frequency (25-50 Hz) vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury.

  18. A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow.

    Science.gov (United States)

    Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong

    2014-07-01

    The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Effect of insulin on the mitotic activity of bone marrow cells after irradiation. [Gamma radiation, rats

    Energy Technology Data Exchange (ETDEWEB)

    Barkalaya, A I

    1976-02-01

    A total of 236 white rats were given a whole-body gamma dose of 750 R. Part of the rats were given a subcutaneous insulin injection of 0.2 units/kg. After 10, 20, 30 min, 1, 2, 3, 5, 8, 10 and 12 hours the mitotic index was determined in both groups of rats in the bone marrow of the femur. The content of glucose and insulin in the blood was determined. The mitotic index was found to be higher on administering insulin. The use of insulin in radiation sickness intensifies the mitotic activity of bone marrow cells and stimulates the recovery of bone marrow hematopoiesis. 5 references.

  20. Usefulness of bone scintigraphic classification and quantitative evaluation of bone mineralization with X-CT and SPECT in renal osteodystrophy

    International Nuclear Information System (INIS)

    Okamura, Terue; Fukuda, Teruo; Inoue, Yuuichi; Koizumi, Yoshiko; Ikeda, Hozumi; Ochi, Hironobu

    1987-01-01

    1. Bone scintigraphy with Tc-99m-MDP was performed on 52 patients with chronic renal failure. These bone scintigrams were classified into 4 groups, each of which was correlated to laboratory data and quantitative data of bone mineralization. Group I (32 patients) showed high accumulation of Tc-99m-MDP in the bone. High level of Alk-Pase and c-PTH, low BMC/BW, low EMI number and high radionuclide activity ratio (RN ratio) were observed. Group II (9 patients) demonstrated nuclear bone images with high background activity. RN ratio was slightly higher than the normal. Group III (11 patients) showed extraosseous accumulation of Tc-99m-MDP in the lung, kidney or soft tissues. One patient belonged to Group I. High level of Ca x P product and slightly high RN ratio were observed. In both Group II and III, BMC/BW and EMI number were normal. Group IV (one patient) showed normal skeletal activity on bone scintigram. The mean duration of hemodialysis was the longest in Group I. Our scintigraphic classification is convenient and might contribute an understanding of patho-physiological bone changes in such patients. 2. Subtotal parathyroidectomy (S-PTX) was employed in 18 of 52 patients on chronic renal failure with secondary hyperparathyroidism. These patients were studied before and after S-PTX using 6 different procedures; conventional radiography, microdensitometry, bone mineral analysis, measurement of EMI number with X-CT (frontal bone), bone scintigraphy, and RN ratio (frontal bone/brain) with SPECT. On the bone scan, the diffuse increased activity in the calvarium became less prominent after S-PTX in all 18 patients. We devised a new method to quantify the bone changes revealed by the bone scan; the RN ratio with SPECT. The ratio decreased markedly after surgery. This method seems to be most useful for detecting dynamic bone changes sensitively and quantitatively. (author)

  1. MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy

    Directory of Open Access Journals (Sweden)

    Guang-yu Zhang

    2015-01-01

    Full Text Available MicroRNA-9 (miR-9 has been shown to promote the differentiation of bone marrow mesenchymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study confirmed that increased autophagic activity improved the efficiency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Results showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron specific enolase and microtubule-associated protein 2 increased in the miR-9 + group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.

  2. Playing with bone and fat

    DEFF Research Database (Denmark)

    Gimble, Jeffrey M.; Zvonic, Sanjin; Floyd, Z. Elisabeth

    2006-01-01

    The relationship between bone and fat formation within the bone marrow microenvironment is complex and remains an area of active investigation. Classical in vitro and in vivo studies strongly support an inverse relationship between the commitment of bone marrow-derived mesenchymal stem cells...

  3. Bone impairment in phenylketonuria is characterized by circulating osteoclast precursors and activated T cell increase.

    Directory of Open Access Journals (Sweden)

    Ilaria Roato

    Full Text Available BACKGROUND: Phenylketonuria (PKU is a rare inborn error of metabolism often complicated by a progressive bone impairment of uncertain etiology, as documented by both ionizing and non- ionizing techniques. METHODOLOGY: Peripheral blood mononuclear cell (PBMC cultures were performed to study osteoclastogenesis, in the presence or absence of recombinant human monocyte-colony stimulating factor (M-CSF and receptor activator of NFκB ligand (RANKL. Flow cytometry was utilized to analyze osteoclast precursors (OCPs and T cell phenotype. Tumour necrosis factor α (TNF-α, RANKL and osteoprotegerin (OPG were quantified in cell culture supernatants by ELISA. The effects of RANKFc and anti-TNF-α antibodies were also investigated to determine their ability to inhibit osteoclastogenesis. In addition, bone conditions and phenylalanine levels in PKU patients were clinically evaluated. PRINCIPAL FINDINGS: Several in vitro studies in PKU patients' cells identified a potential mechanism of bone formation inhibition commonly associated with this disorder. First, PKU patients disclosed an increased osteoclastogenesis compared to healthy controls, both in unstimulated and M-CSF/RANKL stimulated PBMC cultures. OCPs and the measured RANKL/OPG ratio were higher in PKU patients compared to healthy controls. The addition of specific antagonist RANKFc caused osteoclastogenesis inhibition, whereas anti-TNF-α failed to have this effect. Among PBMCs isolated from PKU patients, activated T cells, expressing CD69, CD25 and RANKL were identified. Confirmatory in vivo studies support this proposed model. These in vivo studies included the analysis of osteoclastogenesis in PKU patients, which demonstrated an inverse relation to bone condition assessed by phalangeal Quantitative Ultrasound (QUS. This was also directly related to non-compliance to therapeutic diet reflected by hyperphenylalaninemia. CONCLUSIONS: Our results indicate that PKU spontaneous osteoclastogenesis

  4. Synthesis and in vitro evaluation of bone-seeking superparamagnetic iron oxide nanoparticles as contrast agents for imaging bone metabolic activity.

    Science.gov (United States)

    Panahifar, Arash; Mahmoudi, Morteza; Doschak, Michael R

    2013-06-12

    In this article, we report the synthesis and in vitro evaluation of a new class of nonionizing bone-targeting contrast agents based on bisphosphonate-conjugated superparamagnetic iron oxide nanoparticles (SPIONs), for use in imaging of bone turnover with magnetic resonance imaging (MRI). Similar to bone-targeting (99m)Technetium medronate, our novel contrast agent uses bisphosphonates to impart bone-seeking properties, but replaces the former radioisotope with nonionizing SPIONs which enables their subsequent detection using MRI. Our reported method is relatively simple, quick and cost-effective and results in BP-SPIONs with a final nanoparticle size of 17 nm under electron microscopy technique (i.e., TEM). In-vitro binding studies of our novel bone tracer have shown selective binding affinity (around 65%) for hydroxyapatite, the principal mineral of bone. Bone-targeting SPIONs offer the potential for use as nonionizing MRI contrast agents capable of imaging dynamic bone turnover, for use in the diagnosis and monitoring of metabolic bone diseases and related bone pathology.

  5. Bone scintiscanning updated.

    Science.gov (United States)

    Lentle, B C; Russell, A S; Percy, J S; Scott, J R; Jackson, F I

    1976-03-01

    Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.

  6. A 3-year physical activity intervention program increases the gain in bone mineral and bone width in prepubertal girls but not boys: the prospective copenhagen school child interventions study (CoSCIS).

    Science.gov (United States)

    Hasselstrøm, H A; Karlsson, M K; Hansen, S E; Grønfeldt, V; Froberg, K; Andersen, L B

    2008-10-01

    The aim of this study was to evaluate the effect of increasing the amount of time spent in physical education classes on bone mineral accrual and gain in bone size in prepubertal Danish children. A total of 135 boys and 108 girls, aged 6-8 years, were included in a school-based curriculum intervention program where the usual time spent in physical education classes was doubled to four classes (180 min) per week. The control group comprised age-matched children (62 boys and 76 girls) recruited from a separate community who completed the usual Danish school curriculum of physical activity (90 min/week). Dual-energy X-ray absorptiometry was used to evaluate bone mineral content (BMC; g), bone mineral density (g/cm(2)), and bone width at the calcaneus and distal forearm before and after 3 years of intervention. Anthropometrics and Tanner stages were evaluated on the same occasions. General physical activity was measured with an accelerometer worn for 4 days. In girls, the intervention group had a 12.5% increase (P = 0.04) in distal forearm BMC and a 13.2% increase (P = 0.005) in distal forearm scanned area compared with girls in the control group. No differences were found between the intervention and control groups in boys. Increasing the frequency of physical education classes for prepubertal children is associated with a higher accrual of bone mineral and higher gain in bone size after 3 years in girls but not in boys.

  7. Is a school-based physical activity intervention effective for increasing tibial bone strength in boys and girls?

    Science.gov (United States)

    Macdonald, Heather M; Kontulainen, Saija A; Khan, Karim M; McKay, Heather A

    2007-03-01

    This 16-month randomized, controlled school-based study compared change in tibial bone strength between 281 boys and girls participating in a daily program of physical activity (Action Schools! BC) and 129 same-sex controls. The simple, pragmatic intervention increased distal tibia bone strength in prepubertal boys; it had no effect in early pubertal boys or pre or early pubertal girls. Numerous school-based exercise interventions have proven effective for enhancing BMC, but none have used pQCT to evaluate the effects of increased loading on bone strength during growth. Thus, our aim was to determine whether a daily program of physical activity, Action Schools! BC (AS! BC) would improve tibial bone strength in boys and girls who were pre- (Tanner stage 1) or early pubertal (Tanner stage 2 or 3) at baseline. Ten schools were randomized to intervention (INT, 7 schools) or control (CON, 3 schools). The bone-loading component of AS! BC included a daily jumping program (Bounce at the Bell) plus 15 minutes/day of classroom physical activity in addition to regular physical education. We used pQCT to compare 16-month change in bone strength index (BSI, mg2/mm4) at the distal tibia (8% site) and polar strength strain index (SSIp, mm3) at the tibial midshaft (50% site) in 281 boys and girls participating in AS! BC and 129 same-sex controls. We used a linear mixed effects model to analyze our data. Children were 10.2+/-0.6 years at baseline. Intervention boys tended to have a greater increase in BSI (+774.6 mg2/mm4; 95% CI: 672.7, 876.4) than CON boys (+650.9 mg2/mm4; 95% CI: 496.4, 805.4), but the difference was only significant in prepubertal boys (p=0.03 for group x maturity interaction). Intervention boys also tended to have a greater increase in SSIp (+198.6 mm3; 95% CI: 182.9, 214.3) than CON boys (+177.1 mm3; 95% CI: 153.5, 200.7). Change in BSI and SSIp was similar between CON and INT girls. Our findings suggest that a simple, pragmatic program of daily activity

  8. Use of lymphokine-activated killer cells to prevent bone marrow graft rejection and lethal graft-vs-host disease

    International Nuclear Information System (INIS)

    Azuma, E.; Yamamoto, H.; Kaplan, J.

    1989-01-01

    Prompted by our recent finding that lymphokine-activated killer (LAK) cells mediate both veto and natural suppression, we tested the ability of adoptively transferred LAK cells to block two in vivo alloreactions which complicate bone marrow transplantation: resistance to transplanted allogeneic bone marrow cells, and lethal graft-vs-host disease. Adoptive transfer of either donor type B6D2 or recipient-type B6 lymphokine-activated bone marrow cells, cells found to have strong LAK activity, abrogated or inhibited the resistance of irradiated B6 mice to both B6D2 marrow and third party-unrelated C3H marrow as measured by CFU in spleen on day 7. The ability of lymphokine-activated bone marrow cells to abrogate allogeneic resistance was eliminated by C lysis depletion of cells expressing asialo-GM1, NK1.1, and, to a variable degree, Thy-1, but not by depletion of cells expressing Lyt-2, indicating that the responsible cells had a LAK cell phenotype. Similar findings were obtained by using splenic LAK cells generated by 3 to 7 days of culture with rIL-2. Demonstration that allogeneic resistance could be blocked by a cloned LAK cell line provided direct evidence that LAK cells inhibit allogeneic resistance. In addition to inhibiting allogeneic resistance, adoptively transferred recipient-type LAK cells prevented lethal graft-vs-host disease, and permitted long term engraftment of allogeneic marrow. Irradiation prevented LAK cell inhibition of both allogeneic resistance and lethal graft-vs-host disease. These findings suggest that adoptive immunotherapy with LAK cells may prove useful in preventing graft rejection and graft-versus-host disease in human bone marrow transplant recipients

  9. Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models.

    Science.gov (United States)

    Benito, Juliana; Ramirez, Marc S; Millward, Niki Zacharias; Velez, Juliana; Harutyunyan, Karine G; Lu, Hongbo; Shi, Yue-Xi; Matre, Polina; Jacamo, Rodrigo; Ma, Helen; Konoplev, Sergej; McQueen, Teresa; Volgin, Andrei; Protopopova, Marina; Mu, Hong; Lee, Jaehyuk; Bhattacharya, Pratip K; Marszalek, Joseph R; Davis, R Eric; Bankson, James A; Cortes, Jorge E; Hart, Charles P; Andreeff, Michael; Konopleva, Marina

    2016-04-01

    To characterize the prevalence of hypoxia in the leukemic bone marrow, its association with metabolic and transcriptional changes in the leukemic blasts and the utility of hypoxia-activated prodrug TH-302 in leukemia models. Hyperpolarized magnetic resonance spectroscopy was utilized to interrogate the pyruvate metabolism of the bone marrow in the murine acute myeloid leukemia (AML) model. Nanostring technology was used to evaluate a gene set defining a hypoxia signature in leukemic blasts and normal donors. The efficacy of the hypoxia-activated prodrug TH-302 was examined in the in vitro and in vivo leukemia models. Metabolic imaging has demonstrated increased glycolysis in the femur of leukemic mice compared with healthy control mice, suggesting metabolic reprogramming of hypoxic bone marrow niches. Primary leukemic blasts in samples from AML patients overexpressed genes defining a "hypoxia index" compared with samples from normal donors. TH-302 depleted hypoxic cells, prolonged survival of xenograft leukemia models, and reduced the leukemia stem cell pool in vivo In the aggressive FLT3/ITD MOLM-13 model, combination of TH-302 with tyrosine kinase inhibitor sorafenib had greater antileukemia effects than either drug alone. Importantly, residual leukemic bone marrow cells in a syngeneic AML model remain hypoxic after chemotherapy. In turn, administration of TH-302 following chemotherapy treatment to mice with residual disease prolonged survival, suggesting that this approach may be suitable for eliminating chemotherapy-resistant leukemia cells. These findings implicate a pathogenic role of hypoxia in leukemia maintenance and chemoresistance and demonstrate the feasibility of targeting hypoxic cells by hypoxia cytotoxins. ©2015 American Association for Cancer Research.

  10. Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice

    International Nuclear Information System (INIS)

    Ikeda, Kazuhiro; Tsukui, Tohru; Imazawa, Yukiko; Horie-Inoue, Kuniko; Inoue, Satoshi

    2012-01-01

    Highlights: ► Conditional transgenic mice expressing constitutively active estrogen receptor α (caERα) in chondrocytes were developed. ► Expression of caERα in chondrocytes impaired longitudinal bone growth in mice. ► caERα affects chondrocyte proliferation and differentiation. ► This mouse model is useful for understanding the physiological role of ERαin vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caERα ColII , expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERα ColII mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caERα ColII mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERα ColII mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  11. Unicameral bone cysts treated by injection of bone marrow or methylprednisolone.

    Science.gov (United States)

    Chang, C H; Stanton, R P; Glutting, J

    2002-04-01

    In 79 consecutive patients with unicameral bone cysts we compared the results of aspiration and injection of bone marrow with those of aspiration and injection of steroid. All were treated by the same protocol. The only difference was the substance injected into the cysts. The mean radiological follow-up to detect activity in the cyst was 44 months (12 to 108). Of the 79 patients, 14 received a total of 27 injections of bone marrow and 65 a total of 99 injections of steroid. Repeated injections were required in 57% of patients after bone marrow had been used and in 49% after steroid. No complications were noted in either group. In this series no advantage could be shown for the use of autogenous injection of bone marrow compared with injection of steroid in the management of unicameral bone cysts.

  12. Is bone scintigraphy necessary in the initial surgical staging of chondrosarcoma of bone?

    Energy Technology Data Exchange (ETDEWEB)

    Douis, Hassan; James, Steven L.; Davies, Mark A. [Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom); Grimer, Robert J. [Royal Orthopaedic Hospital, Department of Orthopaedic Oncology, Birmingham (United Kingdom)

    2012-04-15

    To assess the value of whole-body bone scintigraphy in the initial surgical staging of chondrosarcoma of bone. A retrospective review was conducted of the bone scintigraphy reports of a large series of patients with peripheral or central chondrosarcoma of bone treated in a specialist orthopaedic oncology unit over a 13-year period. Abnormal findings were correlated against other imaging, histological grade and the impact on surgical staging. A total of 195 chondrosarcomas were identified in 188 patients. In 120 (63.8%) patients the reports of bone scintigraphy noted increased activity at the site of one or more chondrosarcomas. In one patient the tumour was outside the field-of-view of the scan, and in the remaining 67 (35.6%) cases, there was increased activity at the site of the chondrosarcoma and further abnormal activity in other areas of the skeleton. Causes of these additional areas of activity included degenerative joint disease, Paget's disease and in one case a previously undiagnosed melanoma metastasis. No cases of skeletal metastases from the chondrosarcoma were found in this series. Multifocal chondrosarcomas were identified in three cases. In two it was considered that all the tumours would have been adequately revealed on the initial MR imaging staging studies. In only the third multifocal case was an unsuspected, further presumed low-grade, central chondrosarcoma identified in the opposite asymptomatic femur. Although this case revealed an unexpected finding the impact on surgical staging was limited as it was decided to employ a watch-and-wait policy for this tumour. There is little role for the routine use of whole-body bone scintigraphy in the initial surgical staging in patients with chondrosarcoma of bone irrespective of the histological grade. (orig.)

  13. Short Anabolic Peptides for Bone Growth.

    Science.gov (United States)

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth. © 2016 Wiley Periodicals, Inc.

  14. Live imaging of osteoclast inhibition by bisphosphonates in a medaka osteoporosis model

    Directory of Open Access Journals (Sweden)

    Tingsheng Yu

    2016-02-01

    Full Text Available Osteoclasts are bone-resorbing cells derived from the monocyte/macrophage lineage. Excess osteoclast activity leads to reduced bone mineral density, a hallmark of diseases such as osteoporosis. Processes that regulate osteoclast activity are therefore targeted in current osteoporosis therapies. To identify and characterize drugs for treatment of bone diseases, suitable in vivo models are needed to complement cell-culture assays. We have previously reported transgenic medaka lines expressing the osteoclast-inducing factor receptor activator of nuclear factor κB ligand (Rankl under control of a heat shock-inducible promoter. Forced Rankl expression resulted in ectopic osteoclast formation, as visualized by live imaging in fluorescent reporter lines. This led to increased bone resorption and a dramatic reduction of mineralized matrix similar to the situation in humans with osteoporosis. In an attempt to establish the medaka as an in vivo model for osteoporosis drug screening, we treated Rankl-expressing larvae with etidronate and alendronate, two bisphosphonates commonly used in human osteoporosis therapy. Using live imaging, we observed an efficient, dose-dependent inhibition of osteoclast activity, which resulted in the maintenance of bone integrity despite an excess of osteoclast formation. Strikingly, we also found that bone recovery was efficiently promoted after inhibition of osteoclast activity and that osteoblast distribution was altered, suggesting effects on osteoblast-osteoclast coupling. Our data show that transgenic medaka lines are suitable in vivo models for the characterization of antiresorptive or bone-anabolic compounds by live imaging and for screening of novel osteoporosis drugs.

  15. Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology.

    Science.gov (United States)

    Huesa, Carmen; Ortiz, Ana C; Dunning, Lynette; McGavin, Laura; Bennett, Louise; McIntosh, Kathryn; Crilly, Anne; Kurowska-Stolarska, Mariola; Plevin, Robin; van 't Hof, Rob J; Rowan, Andrew D; McInnes, Iain B; Goodyear, Carl S; Lockhart, John C; Ferrell, William R

    2016-11-01

    Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. OA was induced in wild-type (WT) and PAR2-deficient (PAR2 -/- ) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2 -/- mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2 -/- mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2 -/- mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2 -/- mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology

    Science.gov (United States)

    Huesa, Carmen; Ortiz, Ana C; Dunning, Lynette; McGavin, Laura; Bennett, Louise; McIntosh, Kathryn; Crilly, Anne; Kurowska-Stolarska, Mariola; Plevin, Robin; van ‘t Hof, Rob J; Rowan, Andrew D; McInnes, Iain B; Goodyear, Carl S; Lockhart, John C; Ferrell, William R

    2016-01-01

    Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes. PMID:26698846

  17. Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption

    Directory of Open Access Journals (Sweden)

    Chen-he Zhou

    2018-03-01

    Full Text Available Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Stephania cepharantha Hayata exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK and phosphatidylinositol 3-kinase (PI3K-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist and/or SC79 (an AKT agonist in vitro. Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.

  18. Simulation of 239Pu location in trabecular bone: a computerized model of adult endosteal bone remodeling and its interaction with injected 239Pu

    International Nuclear Information System (INIS)

    Kimmel, D.B.; Jee, W.S.S.

    1979-01-01

    A computer simulation of the relationship of bone microanatomic metabolic activity to the microscopic location of 239 Pu in bone has been attempted. The model incorporates the rate of bone turnover, cell location and density, bone resorptive activity (as it removes 239 Pu from bone), bone formation activity (as it buries 239 Pu in bone), recycling of 239 Pu, and liver translocation of 239 Pu to bone, such that the skeletal retention curve for 239 Pu injected in monomeric form into the young adult beagle is matched. The eventual aim of this work is to calculate the radiation dose to bone cells, knowing the relative location of 239 Pu deposited in bone and the cells that reside at bone surfaces as it changes throughout the lifespan of an animal. Early results indicate that osteosarcoma incidence may be proportional to the number of alpha hits which occur to osteoprogenitor cells and osteoblasts, the dividing cell population found near surfaces where bone turnover is in progress

  19. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo

    Directory of Open Access Journals (Sweden)

    Shengwei He

    2017-01-01

    Full Text Available Objective(s:To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo. Materials and Methods:Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor k-B ligan, and pre-collagen type 1 a were measured. Results:Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor k-B ligand, and pre-collagen type 1 a were also markedly higher following 25 and 50 Hz treatment. Conclusion:Low frequency (25–50 Hz vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury.

  20. Active bone marrow distribution as a function of age in humans

    International Nuclear Information System (INIS)

    Cristy, M.

    1981-01-01

    In response to the need for better quantitative estimates of the regional distribution of the active bone marrow organ in infants and children, a method using various anatomical data has been developed. The method, a refinement of that of Atkinson (1962), predicts that in the newborn 27.8% of the active marrow in the body resides in the skull and 20.7% resides in the lower limbs. Atkinson's method predicts 7.0% in the skull and 38.9% in the lower limbs. According to the experimental data of Hudson (1965) involving 16 late-term foetuses and newborns, there is 29.5% (+- 4.2%) in the skull and 23.7% (+-2.2%) in the lower limbs. The values from the new method are much closer to experimental values in both bone groups. The values for the newborn and age one year predicted by the new method were adjusted after comparison with the experimental data for the newborn. Newer information on marrow cellularity was also incorporated into the method presented here, so that the distribution calculated here for the adult differs somewhat from those calculated by others. Overall, this adult distribution agrees more closely with published distributions based on 59 Fe studies than do the earlier distributions. (author)

  1. A "Bony" Proposition: Pathways Mediating Responses to Simulated Weightlessness and Radiation

    Science.gov (United States)

    Tahimic, Candice; Globus, Ruth

    2016-01-01

    There is evidence that weightlessness and radiation, two elements of the spaceflight environment, can lead to detrimental changes in human musculoskeletal tissue, including bone loss and muscle atrophy. This bone loss is thought to be brought about by the increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. My current area of research focuses on understanding the mechanistic basis for the responses of bone to the spaceflight environment using earth-based animal and cellular models. The overarching goal is to identify molecular targets to prevent bone loss in space exploration and earth-based scenarios of radiotherapy, accidental radiation exposure and reduced mobility. In this talk, I will highlight two signaling pathways that potentially play a role in the response of bone to spaceflight-like conditions. Firstly, I will discuss the role of insulin-like growth factor 1 (IGF1) signaling as it pertains to the recovery of bone from simulated weightlessness (rodent hindlimb unloading model). Secondly, I will share recent findings from our study that aims to understand the emerging role of autophagy in maintaining the balance between bone formation and resorption (bone homeostasis) as well as normal skeletal structure.

  2. Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice.

    Science.gov (United States)

    Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lay, Yu-An E; Lane, Nancy E; Yao, Wei

    2015-12-01

    For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice. To evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue. A TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0mg group, although a higher bone strength was observed in the 10mg group. Surface-based histomorphometry revealed that the 100mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100mg/kg dose. TAM treatment at 100mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can

  3. Enhancement of Bone Marrow-Derived Mesenchymal Stem Cell Osteogenesis and New Bone Formation in Rats by Obtusilactone A

    Directory of Open Access Journals (Sweden)

    Yi-Hsiung Lin

    2017-11-01

    Full Text Available The natural pure compound obtusilactone A (OA was identified in Cinnamomum kotoense Kanehira & Sasaki, and shows effective anti-cancer activity. We studied the effect of OA on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs. OA possesses biocompatibility, stimulates Alkaline Phosphatase (ALP activity and facilitates mineralization of BMSCs. Expression of osteogenesis markers BMP2, Runx2, Collagen I, and Osteocalcin was enhanced in OA-treated BMSCs. An in vivo rat model with local administration of OA via needle implantation to bone marrow-residing BMSCs revealed that OA increased the new bone formation and trabecular bone volume in tibias. Micro-CT images and H&E staining showed more trabecular bone at the needle-implanted site in the OA group than the normal saline group. Thus, OA confers an osteoinductive effect on BMSCs via induction of osteogenic marker gene expression, such as BMP2 and Runx2 expression and subsequently elevates ALP activity and mineralization, followed by enhanced trabecular bone formation in rat tibias. Therefore, OA is a potential osteoinductive drug to stimulate new bone formation by BMSCs.

  4. Bone mineral density, muscle strength and physical activity. A population-based study of 332 subjects aged 15-42 years.

    Science.gov (United States)

    Düppe, H; Gärdsell, P; Johnell, O; Nilsson, B E; Ringsberg, K

    1997-04-01

    The aim of this population-based study was to find out whether differences in levels of physical activity have an influence on bone mass quantity and whether quadriceps muscle strength is a reliable determinant of bone mass. Included were 175 men and 157 women, aged 15-42 years. Bone mineral density (BMD) was measured at various sites by dual X-ray absorptiometry (DXA) and single photon absorptiometry (SPA). Muscle strength was assessed using an isokinetic muscle force meter. A questionnaire was used to estimate the level of physical activity. We found a positive correlation between physical activity and BMD for boys at the distal forearm and for girls at the trochanter (age group 15-16 years). Active men (age group 21-42 years) had up to 9% higher BMD levels at the hip than those who were less active. Quadriceps muscle torque was not an independent predictor of BMD. Our data suggest that a higher level of physical activity-within the limits of a "normal life style"-may have a positive effect on BMD in the proximal femur of young adults, which in turn may lessen the subsequent risk of fracture.

  5. Significance of bone specific alkaline phosphatase as a tumor marker in malignant bone tumor

    International Nuclear Information System (INIS)

    Kim, Sug Jun; Jeon, Dae Geun; Huh, Kwang

    1998-01-01

    The relationship between total alkaline phosphatase activity and bone forming lesion is a well known fact. But alkaline phosphatase consist mainly of two portion (liver, bone). To clarify the exact activity of bone forming tissue, quantitative measurement of BALP is essential. Two finds of tests were performed for their feasibility as a laboratory test (wheat germ lectin vs electrophoresis). We analyzed 40 bony lesion and got 58 samples. Lectin method was simple, economic, with reliable resproducability. Owing to the small number of test sample, we could not identify the relationship between the disease activity and measured BALP level. Further collection of clinical sample and analysis the pattern of BALP on each clinical settings. (author). 8 refs

  6. Osteoblasts Interaction with PLGA Membranes Functionalized with Titanium Film Nanolayer by PECVD. In vitro Assessment of Surface Influence on Cell Adhesion during Initial Cell to Material Interaction

    Science.gov (United States)

    Terriza, Antonia; Vilches-Pérez, José I.; González-Caballero, Juan L.; de la Orden, Emilio; Yubero, Francisco; Barranco, Angel; Gonzalez-Elipe, Agustín R.; Vilches, José; Salido, Mercedes

    2014-01-01

    New biomaterials for Guided Bone Regeneration (GBR), both resorbable and non-resorbable, are being developed to stimulate bone tissue formation. Thus, the in vitro study of cell behavior towards material surface properties turns a prerequisite to assess both biocompatibility and bioactivity of any material intended to be used for clinical purposes. For this purpose, we have developed in vitro studies on normal human osteoblasts (HOB®) HOB® osteoblasts grown on a resorbable Poly (lactide-co-glycolide) (PLGA) membrane foil functionalized by a very thin film (around 15 nm) of TiO2 (i.e., TiO2/PLGA membranes), designed to be used as barrier membrane. To avoid any alteration of the membranes, the titanium films were deposited at room temperature in one step by plasma enhanced chemical vapour deposition. Characterization of the functionalized membranes proved that the thin titanium layer completely covers the PLGA foils that remains practically unmodified in their interior after the deposition process and stands the standard sterilization protocols. Both morphological changes and cytoskeletal reorganization, together with the focal adhesion development observed in HOB osteoblasts, significantly related to TiO2 treated PLGA in which the Ti deposition method described has revealed to be a valuable tool to increase bioactivity of PLGA membranes, by combining cell nanotopography cues with the incorporation of bioactive factors. PMID:28788538

  7. Osteoblasts Interaction with PLGA Membranes Functionalized with Titanium Film Nanolayer by PECVD. In vitro Assessment of Surface Influence on Cell Adhesion during Initial Cell to Material Interaction

    Directory of Open Access Journals (Sweden)

    Antonia Terriza

    2014-03-01

    Full Text Available New biomaterials for Guided Bone Regeneration (GBR, both resorbable and non-resorbable, are being developed to stimulate bone tissue formation. Thus, the in vitro study of cell behavior towards material surface properties turns a prerequisite to assess both biocompatibility and bioactivity of any material intended to be used for clinical purposes. For this purpose, we have developed in vitro studies on normal human osteoblasts (HOB® HOB® osteoblasts grown on a resorbable Poly (lactide-co-glycolide (PLGA membrane foil functionalized by a very thin film (around 15 nm of TiO2 (i.e., TiO2/PLGA membranes, designed to be used as barrier membrane. To avoid any alteration of the membranes, the titanium films were deposited at room temperature in one step by plasma enhanced chemical vapour deposition. Characterization of the functionalized membranes proved that the thin titanium layer completely covers the PLGA foils that remains practically unmodified in their interior after the deposition process and stands the standard sterilization protocols. Both morphological changes and cytoskeletal reorganization, together with the focal adhesion development observed in HOB osteoblasts, significantly related to TiO2 treated PLGA in which the Ti deposition method described has revealed to be a valuable tool to increase bioactivity of PLGA membranes, by combining cell nanotopography cues with the incorporation of bioactive factors.

  8. Management of pediatric mandibular fractures using bioresorbable plating system - Efficacy, stability, and clinical outcomes: Our experiences and literature review.

    Science.gov (United States)

    Singh, Mahinder; Singh, R K; Passi, Deepak; Aggarwal, Mohit; Kaur, Guneet

    2016-01-01

    The purpose of this study was to determine the efficacy and stability of the biodegradable fixation system for treatment of mandible fractures in pediatric patients by measuring the bite force. Sixty pediatric patients with mandibular fractures (36 males, 24 females) were included in this study. The 2.5-mm resorbable plates were adapted along Champy's line of ideal osteosynthesis and secured with four 2.5 mm diameter monocortical resorbable screws, 8 mm in length. All patients were followed for 10 months. Clinical parameters, such as soft tissue infection, nonunion, malunion, implant exposure, malocclusion, nerve injury, and bite force for stability, were prospectively assessed. Adequate fixation and primary bone healing was achieved in 100% of the cases. Six minor complications (10%) were observed: 2 soft tissue infections (3%), 1 plate dehiscence (2%), 1 malocclusion (2%), and 2 paresthesia (3%). 2.5-mm resorbable plating system along Champy's line of ideal osteosynthesis is a good treatment modality for mandible fractures in pediatric patients.

  9. Topical Treatment with Xiaozheng Zhitong Paste (XZP Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

    Directory of Open Access Journals (Sweden)

    Yanju Bao

    2015-01-01

    Full Text Available To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05. Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all. Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

  10. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

  11. The effects of Zinc supplementation on serum zinc, alkaline phosphatase activity and fracture healing of bones

    International Nuclear Information System (INIS)

    Sadighi, A.; Moradi, A.; Roshan, Marjan M.; Ostadrahimi, A.

    2009-01-01

    Objective was to determine the effect of zinc supplementation on callus information, serum zinc and alkaline phosphatase activity in humans. This randomized, double-blind, placebo controlled clinical trial was conducted on 60 patients with traumatic bone fracture referred to Shohada Hospital of Tabriz, Iran from August to December 2007. Subjects were randomly divided into 2 groups: cases (n=30), receiving one capsule of zinc sulfate consists of 50 mg zinc each day and the controls (n=30), receiving placebo for 60 days. Individual and clinical information was determined by a questionnaire: nutritional intake by 3 days food records at the beginning and the end of trial. Serum zinc and alkaline phosphatase was measured by atomic absorption spectroscopy and by enzymatic method. Callus information during fracture healing was evaluated by radiography of the bone. There was no significant difference in physical activity, gender, age, type of fractures and nutrient intake, between the 2 groups. The administration of zinc caused a significant elevation of serum zinc and alkaline phosphatase activity. Assessment of bone x-rays showed a significant progress in callus formation in cases compared to the controls. This study shows that zinc supplementation can stimulate fracture healing, however, it needs further study. (author)

  12. Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

    Science.gov (United States)

    Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

    2016-05-01

    Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

  13. The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Furukawa, Yohji; Tanaka, Hiroyoshi

    1994-01-01

    Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of 99m Tc-hydroxymethylene diphosphonate(HMDP). The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformance were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, γ-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases. (author)

  14. The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Nobuaki; Fukunaga, Masao; Furukawa, Yohji; Tanaka, Hiroyoshi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    1994-06-01

    Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of [sup 99m]Tc-hydroxymethylene diphosphonate(HMDP). The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformance were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, [gamma]-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases. (author).

  15. Three dimensional evaluation of alveolar bone changes in response to different rapid palatal expansion activation rates

    Directory of Open Access Journals (Sweden)

    Brian LaBlonde

    Full Text Available ABSTRACT Introduction: The aim of this multi-center retrospective study was to quantify the changes in alveolar bone height and thickness after using two different rapid palatal expansion (RPE activation protocols, and to determine whether a more rapid rate of expansion is likely to cause more adverse effects, such as alveolar tipping, dental tipping, fenestration and dehiscence of anchorage teeth. Methods: The sample consisted of pre- and post-expansion records from 40 subjects (age 8-15 years who underwent RPE using a 4-banded Hyrax appliance as part of their orthodontic treatment to correct posterior buccal crossbites. Subjects were divided into two groups according to their RPE activation rates (0.5 mm/day and 0.8 mm/day; n = 20 each group. Three-dimensional images for all included subjects were evaluated using Dolphin Imaging Software 11.7 Premium. Maxillary base width, buccal and palatal cortical bone thickness, alveolar bone height, and root angulation and length were measured. Significance of the changes in the measurements was evaluated using Wilcoxon signed-rank test and comparisons between groups were done using ANOVA. Significance was defined at p ≤ 0.05. Results: RPE activation rates of 0.5 mm per day (Group 1 and 0.8 mm per day (Group 2 caused significant increase in arch width following treatment; however, Group 2 showed greater increases compared to Group 1 (p < 0.01. Buccal alveolar height and width decreased significantly in both groups. Both treatment protocols resulted in significant increases in buccal-lingual angulation of teeth; however, Group 2 showed greater increases compared to Group 1 (p < 0.01. Conclusion: Both activation rates are associated with significant increase in intra-arch widths. However, 0.8 mm/day resulted in greater increases. The 0.8 mm/day activation rate also resulted in more increased dental tipping and decreased buccal alveolar bone thickness over 0.5 mm/day.

  16. Bone scintigraphy on chronic hemodialyzed patients

    International Nuclear Information System (INIS)

    Koizumi, Yoshiko

    1990-01-01

    Patients with renal osteodystrophy (ROD) are classified into four types (secondary hyperparathyroidism: HPT, osteomalasia, ectopic calcification and normal bone scintigram type) according to findings of whole body bone scintigrams. Markedly high accumulations of Tc-99m-MDP are seen in the skull, especially in patients with HPT. For a quantitative evaluation of bone mineral dynamics, factor analysis (FA) was performed on bone scintigraphy in 36 patients with ROD and in 17 controls. Four were examined before and after parathyroidectomy (PTX). In the early phase (20 min) of bone scintigraphy, the bone factor was clearly extracted by FA. Two original parameters were calculated, one is bone radionuclide (RN) uptake count (BUC), the product of the total RN uptake count of the head and the contribution ratio, the other is bone RN uptake count ratio (BUR) derived by the time activity curve (physiological component of bone) of FA. Bone factor shown by FA is significantly different among patients with HPT, osteomalasia and controls. The value of BUC in patients with HPT is high compared to findings in the controls. The results of FA of ROD correlate well with planar images of bone scintigrams and with data on bone minerals, measured by quantitative methods such as single photon absorptiometry, CT attenuation number of the frontal bone, RN activity ratio ([frontal bone]/[brain]), using SPECT of bone scan. In the cases of PTX, the value of BUC was improved compared to preoperative data. FA of bone scintigraphy is a sensitive and useful method for quantitative evaluation of bone mineral dynamics and to assess the therapeutic effects in ROD. (author)

  17. Hake fish bone as a calcium source for efficient bone mineralization.

    Science.gov (United States)

    Flammini, Lisa; Martuzzi, Francesca; Vivo, Valentina; Ghirri, Alessia; Salomi, Enrico; Bignetti, Enrico; Barocelli, Elisabetta

    2016-01-01

    Calcium is recognized as an essential nutritional factor for bone health. An adequate intake is important to achieve or maintain optimal bone mass in particular during growth and old age. The aim of the present study was to evaluate the efficiency of hake fish bone (HBF) as a calcium source for bone mineralization: in vitro on osteosarcoma SaOS-2 cells, cultured in Ca-free osteogenic medium (OM) and in vivo on young growing rats fed a low-calcium diet. Lithotame (L), a Ca supplement derived from Lithothamnium calcareum, was used as control. In vitro experiments showed that HBF supplementation provided bone mineralization similar to standard OM, whereas L supplementation showed lower activity. In vivo low-Ca HBF-added and L-added diet similarly affected bone deposition. Physico-chemical parameters concerning bone mineralization, such as femur breaking force, tibia density and calcium/phosphorus mineral content, had beneficial effects from both Ca supplementations, in the absence of any evident adverse effect. We conclude HBF derived from by-product from the fish industry is a good calcium supplier with comparable efficacy to L.

  18. Bone marrow scintigraphy vs bone scintigraphy and radiography in multiple myeloma

    International Nuclear Information System (INIS)

    Feggi, M.; Prandini, N.; Orzincolo, C.; Bagni, B.; Scutellari, P.N.; Spanedda, R.; Gennari, M.; Scapoli, C.L.

    1988-01-01

    The radiography patterns of the skeleton of 73 patients affected by multiple myeloma (MM) were compared to the correspondent scintigraphic findings. Whole body scans were performed using Tc-diphosphonates 99m (bone scintigraphy). And Tc-microcolloides 99m (bone marrow scintigraphy). The results indicate that: a) radiography is more sensitive and accurate than scintigraphy in detecting typical myeloma-related bone lesions; b) bone scintigraphy is useful in detecting alterations in particular locations-i.e. sternum, ribs, scapulae, etc.-which are difficult to demonstrate by plain X-rays; moreover, the recovery of the fractures can be visualized; c) bone marrow scintigraphy is employed to demonstrate the presence of marrow expasion, of cold/hot spots, and relative marrow uptake, related to phagocytic activity. Since in adult men red marrow is confined to the epiphysis of long bones and to the spine, all the diseases affecting bone marrow cause medullary expansion/reduction, which are both easily detected by specific radiopharmaceuticals. The peripheral expasions is clearly documented especially in distal humeri and femora since marrow uptake is included, in healthy adults, in the axial and proximal appendicular skeleton. In spite of its yielding unique informetion, bone marrow scintigraphy remains an additional technique of bone scan, because of its low diagnoditc accuracy

  19. Potential of Resveratrol Analogues as Antagonists of Osteoclasts and Promoters of Osteoblasts

    DEFF Research Database (Denmark)

    Kupisiewicz, Katarzyna; Boissy, Patrice; Abdallah, Basem M

    2010-01-01

    The plant phytoalexin resveratrol was previously demonstrated to inhibit the differentiation and bone resorbing activity of osteoclasts, to promote the formation of osteoblasts from mesenchymal precursors in cultures, and inhibit myeloma cell proliferation, when used at high concentrations....... In the current study, we screened five structurally modified resveratrol analogues for their ability to modify the differentiation of osteoclasts and osteoblasts and proliferation of myeloma cells. Compared to resveratrol, analogues showed an up to 5,000-fold increased potency to inhibit osteoclast...... differentiation. To a lesser extent, resveratrol analogues also promoted osteoblast maturation. However, they did not antagonize the proliferation of myeloma cells. The potency of the best-performing candidate in vitro was tested in vivo in an ovariectomy-induced model of osteoporosis, but an effect on bone loss...

  20. Mandibular Overdentures Supported by 6-mm Dental Implants : A 1-Year Prospective Cohort Study

    NARCIS (Netherlands)

    Gulje, Felix; Raghoebar, Gerry M.; Ter Meulen, Jan-Willem P.; Vissink, Arjan; Meijer, Henny J. A.; Guljé, Felix

    Background: The extremely resorbed edentulous mandible, with a bone height of 8 mm or less, is still a challenge in implant dentistry. Recently, dental implants of 6 mm in length have been developed. Purpose: The purpose of this 1-year prospective cohort study was to evaluate treatment outcome of