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Sample records for prevented bone loss

  1. Policosanol prevents bone loss in ovariectomized rats.

    Science.gov (United States)

    Noa, M; Más, R; Mendoza, S; Gámez, R; Mendoza, N; González, J

    2004-01-01

    Osteoporosis is characterized by reduced bone mass, abnormal bone architecture and increased fracture risk. Ovariectomy impairs bone mass and metabolism in rats and ovariectomized rats are considered as a suitable model of postmenopausal osteoporosis. Mevalonate is required for producing lipoids that are important in osteoclast activity and thus drugs affecting mevalonate production can prevent bone loss in rodents. Policosanol is a cholesterol-lowering drug isolated from sugar cane wax that inhibits cholesterol biosynthesis through an indirect regulation of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity. The purpose of this study was to determine whether policosanol could prevent bone loss in the bones of ovariectomized rats by comparing its effects with those induced by estradiol. Sprague Dawley female rats were randomly distributed in four groups: a sham-operated group treated with Tween/H2O vehicle and three groups of ovariectomized rats treated with 17beta-estradiol (30 microg/kg/day) or policosanol (50 and 200 mg/kg/day), respectively, for 3 months. At treatment completion the rats were sacrificed, their bones removed and variables of bone resorption and formation were investigated by histomorphometry. Ovariectomy increased trabecular separation but diminished the number and thickness of trabecules. Estradiol and policosanol prevented these effects compared with ovariectomized controls. Both treatments also prevented an increase in the number of osteoclasts and their surface area induced by ovariectomy. Estradiol, but not policosanol, significantly prevented an increase of osteoblast surface area compared with ovariectomized controls. In conclusion, policosanol prevented bone loss and decreased bone resorption in ovariectomized rats, suggesting that it should be potentially useful in preventing bone loss in postmenopausal women.

  2. Does platform switching really prevent crestal bone loss around implants?

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Hagiwara

    2010-08-01

    Full Text Available To maintain long-term implant stability, it is important to minimize bone loss around the implant. Several clinical studies have shown a mean marginal bone loss around dental implants of 1.5–2 mm in the first year after prosthetic restoration. Currently, concepts to prevent bone loss around dental implants have been reported as the platform switching (PLS. This technique use of prosthetic abutments with reduced width in relation to the implant platform diameter seems to have the greatest potential to limit the crestal resorption. However, there are only a few reports on the mechanism of action or the extent of bone loss prevention, and as such, it is difficult to say that the effect of PLS has been thoroughly examined. Excluding case reports, articles on PLS can be broadly categorized into: (1 radiographic evaluation of crestal bone level in humans, (2 histological and histomorphometrical analysis in animals, or (3 finite element analysis. This review revealed a shortage of published data for above three categories related PLS. Researchers have attempted to explain the mechanism of action of PLS; however, it is necessary to conduct further studies, including histological studies using animals, to clarify the mechanism fully.

  3. Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss.

    Science.gov (United States)

    Zhang, Yong; Guan, Hanfeng; Li, Jing; Fang, Zhong; Chen, Wenjian; Li, Feng

    2015-09-04

    The activity of protein kinases IKK-ε and TANK-binding kinase 1 (TBK1) has been shown to be associated with inflammatory diseases. As an inhibitor of IKK-ε and TBK1, amlexanox is an anti-inflammatory, anti-allergic, immunomodulator and used for treatment of ulcer, allergic rhinitis and asthma in clinic. We hypothesized that amlexanox may be used for treatment of osteoclast-related diseases which frequently associated with a low grade of systemic inflammation. In this study, we investigated the effects of amlexanox on RANKL-induced osteoclastogenesis in vitro and ovariectomy-mediated bone loss in vivo. In primary bone marrow derived macrophages (BMMs), amlexanox inhibited osteoclast formation and bone resorption. At the molecular level, amlexanox suppressed RANKL-induced activation of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPKs), c-Fos and NFATc1. Amlexanox decreased the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. Moreover, amlexanox enhanced osteoblast differentiation of BMSCs. In ovariectomized (OVX) mouse model, amlexanox prevented OVX-induced bone loss by suppressing osteoclast activity. Taken together, our results demonstrate that amlexanox suppresses osteoclastogenesis and prevents OVX-induced bone loss. Therefore, amlexanox may be considered as a new therapeutic candidate for osteoclast-related diseases, such as osteoporosis and rheumatoid arthritis.

  4. 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.

  5. Donepezil prevents RANK-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Sato

    2015-09-01

    Conclusions: AChE promotes osteoclast differentiation in vitro. Donepezil inhibits osteoclast function in vitro and prevents bone loss by suppressing bone resorption in vivo, suggesting the possibility that donepezil reduces fracture risk in patients with Alzheimer's disease.

  6. Vitamin K supplementation does not prevent bone loss in ovariectomized Norway rats

    Science.gov (United States)

    Despite plausible biological mechanisms, the differential abilities of phylloquinone (PK) and menaquinones (MKn) to prevent bone loss remain controversial. The objective of the current study was to compare the effects of PK, menaquinone-4 (MK-4) and menaquinone-7(MK-7) on the rate of bone loss in o...

  7. Total glucosides of paeony prevents juxta-articular bone loss in experimental arthritis

    OpenAIRE

    Wei, Chen Chao; You, Fan Tian; Mei, Li Yu; Jian, Sun; Qiang, Chen Yong

    2013-01-01

    Background Total glucosides of paeony (TGP) is a biologically active compound extracted from Paeony root. TGP has been used in rheumatoid arthritis therapy for many years. However, the mechanism by which TGP prevents bone loss has been less explored. Methods TGP was orally administered for 3?months to New Zealand rabbits with antigen-induced arthritis (AIA). Digital x-ray knee images and bone mineral density (BMD) measurements of the subchondral knee bone were performed before sacrifice. Chon...

  8. Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation)

    OpenAIRE

    McGee-Lawrence, Meghan E.; Wojda, Samantha J.; Barlow, Lindsay N.; Drummer, Thomas D.; Castillo, Alesha B.; Kennedy, Oran; Condon, Keith W.; Auger, Janene; Black, Hal L.; Nelson, O. Lynne; Robbins, Charles T.; Donahue, Seth W.

    2009-01-01

    Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus a...

  9. Evidence that increased calcium intake does not prevent early postmenopausal bone loss

    DEFF Research Database (Denmark)

    Hosking, D J; Ross, P D; Thompson, D E

    1998-01-01

    Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium...... intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose...... were not significantly associated with changes in BMD or bone turnover. Even women whose total calcium intake was >1333 mg/d (the highest tertile of total calcium intake) showed a decline in BMD of almost 2%, similar to declines in the lower two tertiles of total calcium intake (

  10. Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group

    DEFF Research Database (Denmark)

    McClung, M; Clemmesen, B; Daifotis, A

    1998-01-01

    BACKGROUND: Preventing bone loss associated with menopause and aging and maintaining the normal micro-architecture of bone provide important opportunities for the prevention of osteoporosis and fractures. OBJECTIVE: To determine the safety and efficacy of alendronate, an aminobisphosphonate, for ...

  11. Two Different Isomers of Vitamin E Prevent Bone Loss in Postmenopausal Osteoporosis Rat Model

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    Norliza Muhammad

    2012-01-01

    Full Text Available Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function, a condition associated with increased free radicals. Vitamin E, a lipid-soluble vitamin, is a potent antioxidant which can scavenge free radicals in the body. In this study, we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats. Three-month-old female Wistar rats were randomly divided into ovariectomized control, sham-operated, and ovariectomized rats treated with either alpha-tocopherol or tocotrienol. Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis. Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume (BV/TV and trabecular number (Tb.N and an increase in trabecular separation (Tb.S. The increase in osteoclast surface (Oc.S and osteoblast surface (Ob.S in ovariectomy indicates an increase in bone turnover rate. Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb.N as well as the increase in Tb.S, while reducing the Oc.S and increasing the Ob.S. In conclusion, the two forms of vitamin E were able to prevent bone loss due to ovariectomy. Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model.

  12. Andrographolide prevents human breast cancer-induced osteoclastic bone loss via attenuated RANKL signaling.

    Science.gov (United States)

    Zhai, Zanjing; Qu, Xinhua; Yan, Wei; Li, Haowei; Liu, Guangwang; Liu, Xuqiang; Tang, Tingting; Qin, An; Dai, Kerong

    2014-02-01

    Bone metastasis is a common and serious complication in advanced cancers such as breast cancer, prostate cancer, and multiple myeloma. Agents that prevent bone loss could be used to develop an alternative therapy for bone metastasis. RANKL, a member of the tumor necrosis factor superfamily, has been shown to play a significant role in cancer-associated bone loss. In this study, we examined the efficacy of the natural compound andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata, in reducing breast cancer-induced osteolysis. AP prevented human breast cancer-induced bone loss by suppressing RANKL-mediated and human breast cancer cell-induced osteoclast differentiation. Molecular analysis revealed that AP prevented osteoclast function by inhibiting RANKL-induced NF-κB and ERK signaling pathway in lower dose (20 μM), as well as inducing apoptosis at higher dose (40 μM). Thus, AP is a potent inhibitor of breast cancer-induced bone metastasis.

  13. GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women.

    Science.gov (United States)

    Iepsen, Eva W; Lundgren, Julie R; Hartmann, Bolette; Pedersen, Oluf; Hansen, Torben; Jørgensen, Niklas R; Jensen, Jens-Erik B; Holst, Jens J; Madsbad, Sten; Torekov, Signe S

    2015-08-01

    Recent studies indicate that glucagon-like peptide (GLP)-1 regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. To investigate the role of GLP-1 RAs on bone formation and weight loss-induced bone mass reduction. Randomized control study. Outpatient research hospital clinic. Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m(2) and age 46 ± 2 years. After a low-calorie-diet-induced 12% weight loss, participants were randomized to treatment with or without administration of the GLP-1 RA liraglutide (1.2 mg/d) for 52 weeks. In case of weight gain, up to two meals per day could be replaced with a low-calorie-diet product to maintain the weight loss. Total, pelvic, and arm-leg bone mineral content (BMC) and bone markers [C-terminal telopeptide of type 1 collagen (CTX-1) and N-terminal propeptide of type 1 procollagen (P1NP)] were investigated before and after weight loss and after 52-week weight maintenance. Primary endpoints were changes in BMC and bone markers after 52-week weight maintenance with or without GLP-1 RA treatment. Total, pelvic, and arm-leg BMC decreased during weight maintenance in the control group (P GLP-1 RA increased bone formation by 16% and prevented bone loss after weight loss obtained through a low-calorie diet, supporting its role as a safe weight-lowering agent.

  14. Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis.

    Science.gov (United States)

    Garimella, Manasa G; Kour, Supinder; Piprode, Vikrant; Mittal, Monika; Kumar, Anil; Rani, Lekha; Pote, Satish T; Mishra, Gyan C; Chattopadhyay, Naibedya; Wani, Mohan R

    2015-12-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-α, IL-17, and IL-1β. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Suppression of NADPH oxidases prevents chronic ethanol-induced bone loss

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    Since the molecular mechanisms through which chronic excessive alcohol consumption induces osteopenia and osteoporosis are largely unknown, potential treatments for prevention of alcohol-induced bone loss remain unclear. We have previously demonstrated that, chronic ethanol (EtOH) treatment leads to...

  16. Alendronate and estrogen-progestin in the long-term prevention of bone loss

    DEFF Research Database (Denmark)

    Ravn, Pernille; Bidstrup, M; Wasnich, R D

    1999-01-01

    BACKGROUND: Up to 3 years of treatment with alendronate, 5 mg/d, prevents postmenopausal bone loss. OBJECTIVE: To determine whether the effect of alendronate is sustained at 4 years of treatment and persists after treatment is discontinued. DESIGN: Randomized, controlled trial. SETTING: United St...

  17. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    Directory of Open Access Journals (Sweden)

    Liao Cui

    Full Text Available Glucocorticoid (GC induced osteoporosis (GIO is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1 In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2 In vitro study: In concentration from 10(-6 mol/L to 10(-7 mol/L, Sal B stimulated bone marrow stromal cell (MSC differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin m

  18. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

    OpenAIRE

    McGee, Meghan E.; Maki, Aaron J.; Johnson, Steven E.; Lynne Nelson, O.; Robbins, Charles T.; Donahue, Seth W.

    2007-01-01

    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. ...

  19. Blocking antibody to the beta-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

    Science.gov (United States)

    Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins three years prior to the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during the late peri-men...

  20. Targeting cellular senescence prevents age-related bone loss in mice.

    Science.gov (United States)

    Farr, Joshua N; Xu, Ming; Weivoda, Megan M; Monroe, David G; Fraser, Daniel G; Onken, Jennifer L; Negley, Brittany A; Sfeir, Jad G; Ogrodnik, Mikolaj B; Hachfeld, Christine M; LeBrasseur, Nathan K; Drake, Matthew T; Pignolo, Robert J; Pirtskhalava, Tamar; Tchkonia, Tamara; Oursler, Merry Jo; Kirkland, James L; Khosla, Sundeep

    2017-09-01

    Aging is associated with increased cellular senescence, which is hypothesized to drive the eventual development of multiple comorbidities. Here we investigate a role for senescent cells in age-related bone loss through multiple approaches. In particular, we used either genetic (i.e., the INK-ATTAC 'suicide' transgene encoding an inducible caspase 8 expressed specifically in senescent cells) or pharmacological (i.e., 'senolytic' compounds) means to eliminate senescent cells. We also inhibited the production of the proinflammatory secretome of senescent cells using a JAK inhibitor (JAKi). In aged (20- to 22-month-old) mice with established bone loss, activation of the INK-ATTAC caspase 8 in senescent cells or treatment with senolytics or the JAKi for 2-4 months resulted in higher bone mass and strength and better bone microarchitecture than in vehicle-treated mice. The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function, enhances insulin sensitivity, and reduces frailty, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.

  1. Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

    Science.gov (United States)

    McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2009-12-01

    Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.

  2. Sappanone A inhibits RANKL-induced osteoclastogenesis in BMMs and prevents inflammation-mediated bone loss.

    Science.gov (United States)

    Choo, Young-Yeon; Tran, Phuong Thao; Min, Byung-Sun; Kim, Okwha; Nguyen, Hai Dang; Kwon, Seung-Hae; Lee, Jeong-Hyung

    2017-11-01

    Receptor activator of nuclear factor-kB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Suppressing osteoclastogenesis is considered an effective therapeutic approach for bone-destructive diseases, such as osteoporosis and rheumatoid arthritis. Sappanone A (SPNA), a homoisoflavanone compound isolated from the heartwood of Caesalpinia sappan, has been reported to exert anti-inflammatory effects; however, the effects of SPNA on osteoclastogenesis have not been investigated. In the present study, we describe for the first time that SPNA inhibits RANKL-induced osteoclastogenesis in mouse bone marrow macrophages (BMMs) and suppresses inflammation-induced bone loss in a mouse model. SPNA inhibited the formation of osteoclasts from BMMs, osteoclast actin-ring formation, and bone resorption in a concentration-dependent manner. At the molecular level, SPNA significantly inhibited RANKL-induced activation of the AKT/glycogen synthase kinase-3β (GSK-3β) signaling pathway without affecting its activation of the mitogen-activated protein kinases (MAPKs) JNK, p38, and ERK. In addition, SPNA suppressed the induction of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which is a crucial transcription factor in osteoclast differentiation. As a result, SPNA decreased osteoclastogenesis-related marker gene expression, including CtsK, TRAP, dendritic cell-specific transmembrane protein (DC-STAMP), MMP-9 and osteoclast-associated receptor (OSCAR). In a mouse inflammatory bone loss model, SPNA significantly inhibited lipopolysaccharide (LPS)-induced bone loss by suppressing the number of osteoclasts. Taken together, these findings suggest that SPNA inhibits osteoclastogenesis and bone resorption by inhibiting the AKT/GSK-3β signaling pathway and may be a potential candidate compound for the prevention and/or treatment of inflammatory bone loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. High-impact exercise in rats prior to and during suspension can prevent bone loss

    International Nuclear Information System (INIS)

    Yanagihara, G.R.; Paiva, A.G.; Gasparini, G.A.; Macedo, A.P.; Frighetto, P.D.; Volpon, J.B.; Shimano, A.C.

    2016-01-01

    High-impact exercise has been considered an important method for treating bone loss in osteopenic experimental models. In this study, we investigated the effects of osteopenia caused by inactivity in femora and tibiae of rats subjected to jump training using the rat tail suspension model. Eight-week-old female Wistar rats were divided into five groups (n=10 each group): jump training for 2 weeks before suspension and training during 3 weeks of suspension; jump training for 2 weeks before suspension; jump training only during suspension; suspension without any training; and a control group. The exercise protocol consisted of 20 jumps/day, 5 days/week, with a jump height of 40 cm. The bone mineral density of the femora and tibiae was measured by double energy X-ray absorptiometry and the same bones were evaluated by mechanical tests. Bone microarchitecture was evaluated by scanning electron microscopy. One-way ANOVA was used to compare groups. Significance was determined as P<0.05. Regarding bone mineral density, mechanical properties and bone microarchitecture, the beneficial effects were greater in the bones of animals subjected to pre-suspension training and subsequently to training during suspension, compared with the bones of animals subjected to pre-suspension training or to training during suspension. Our results indicate that a period of high impact exercise prior to tail suspension in rats can prevent the installation of osteopenia if there is also training during the tail suspension

  4. High-impact exercise in rats prior to and during suspension can prevent bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Yanagihara, G.R.; Paiva, A.G.; Gasparini, G.A.; Macedo, A.P. [Laboratório de Bioengenharia, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Frighetto, P.D. [Instituto Federal de Educação, Ciência e Tecnologia de São Paulo, São Paulo, SP (Brazil); Volpon, J.B.; Shimano, A.C. [Laboratório de Bioengenharia, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2016-02-02

    High-impact exercise has been considered an important method for treating bone loss in osteopenic experimental models. In this study, we investigated the effects of osteopenia caused by inactivity in femora and tibiae of rats subjected to jump training using the rat tail suspension model. Eight-week-old female Wistar rats were divided into five groups (n=10 each group): jump training for 2 weeks before suspension and training during 3 weeks of suspension; jump training for 2 weeks before suspension; jump training only during suspension; suspension without any training; and a control group. The exercise protocol consisted of 20 jumps/day, 5 days/week, with a jump height of 40 cm. The bone mineral density of the femora and tibiae was measured by double energy X-ray absorptiometry and the same bones were evaluated by mechanical tests. Bone microarchitecture was evaluated by scanning electron microscopy. One-way ANOVA was used to compare groups. Significance was determined as P<0.05. Regarding bone mineral density, mechanical properties and bone microarchitecture, the beneficial effects were greater in the bones of animals subjected to pre-suspension training and subsequently to training during suspension, compared with the bones of animals subjected to pre-suspension training or to training during suspension. Our results indicate that a period of high impact exercise prior to tail suspension in rats can prevent the installation of osteopenia if there is also training during the tail suspension.

  5. Medicines and Bone Loss

    Science.gov (United States)

    Fact Sheet Medici a ne n s d Bone Loss Some types of medicines can cause bone loss, making your bones weak, if used for a long time. Use over a short time ... old bone and replaces it with new bone. Bone loss occurs when old bone breaks down faster than ...

  6. Donepezil prevents RANK-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase.

    Science.gov (United States)

    Sato, Tsuyoshi; Enoki, Yuichiro; Sakamoto, Yasushi; Yokota, Kazuhiro; Okubo, Masahiko; Matsumoto, Masahito; Hayashi, Naoki; Usui, Michihiko; Kokabu, Shoichiro; Mimura, Toshihide; Nakazato, Yoshihiko; Araki, Nobuo; Fukuda, Toru; Okazaki, Yasushi; Suda, Tatsuo; Takeda, Shu; Yoda, Tetsuya

    2015-09-01

    Donepezil, an inhibitor of acetylcholinesterase (AChE) targeting the brain, is a common medication for Alzheimer's disease. Interestingly, a recent clinical study found that administration of this agent is associated with lower risk of hip fracture independently of falling, suggesting its direct effect on bone tissues as well. AChE has been reported to be involved in osteoblast function, but the role of AChE on osteoclastogenesis still remains unclear. We analyzed the effect of AChE and donepezil on osteoclastogenesis in vivo and in vitro. Cell-based assays were conducted using osteoclasts generated in cultures of murine bone marrow macrophages (BMMs) with receptor activator of nuclear factor-kappa B ligand (RANKL). The effect of donepezil was also determined in vivo using a mouse model of RANKL-induced bone loss. Recombinant AChE in BMMs cultured with RANKL further promoted RANKL-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast differentiation. RANKL also upregulated AChE expression in BMMs. RNA interference-mediated knockdown of AChE significantly inhibited RANKL-induced osteoclast differentiation and suppressed gene expression specific for osteoclasts. AChE upregulated expression of RANK, the receptor of RANKL, in BMMs. Donepezil decreased cathepsin K expression in BMMs and the resorptive function of osteoclasts on dentine slices. Donepezil decreased RANK expression in BMMs, resulting in the inhibition of osteoclast differentiation with downregulation of c-Fos and upregulation of Id2. Moreover, administration of donepezil prevented RANKL-induced bone loss in vivo, which was associated with the inhibition of bone resorption by osteoclasts. AChE promotes osteoclast differentiation in vitro. Donepezil inhibits osteoclast function in vitro and prevents bone loss by suppressing bone resorption in vivo, suggesting the possibility that donepezil reduces fracture risk in patients with Alzheimer's disease.

  7. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis

    Science.gov (United States)

    Chen, Xiao; Zhi, Xin; Pan, Panpan; Cui, Jin; Cao, Liehu; Weng, Weizong; Zhou, Qirong; Wang, Lin; Zhai, Xiao; Zhao, Qingiie; Hu, Honggang; Huang, Biaotong; Su, Jiacan

    2017-01-01

    Osteoporosis is a metabolic bone disease characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content. The imbalance between osteogenesis by osteoblasts and osteoclastogenesis by osteoclasts contributes to the pathogenesis of postmenopausal osteoporosis. Estrogen withdrawal leads to increased levels of proinflammatory cytokines. Overactivated osteoclasts by inflammation play a vital role in the imbalance. Matrine is an alkaloid found in plants from the Sophora genus with various pharmacological effects, including anti-inflammatory activity. Here we demonstrate that matrine significantly prevented ovariectomy-induced bone loss and inhibited osteoclastogenesis in vivo with decreased serum levels of TRAcp5b, TNF-α, and IL-6. In vitro matrine significantly inhibited osteoclast differentiation induced by receptor activator for NF-κB ligand (RANKL) and M-CSF in bone marrow monocytes and RAW264.7 cells as demonstrated by tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption through pit formation assays. For molecular mechanisms, matrine abrogated RANKL-induced activation of NF-κB, AKT, and MAPK pathways and suppressed osteoclastogenesis-related marker expression, including matrix metalloproteinase 9, NFATc1, TRAP, C-Src, and cathepsin K. Our study demonstrates that matrine inhibits osteoclastogenesis through modulation of multiple pathways and that matrine is a promising agent in the treatment of osteoclast-related diseases such as osteoporosis.—Chen, X., Zhi, X., Pan, P., Cui, J., Cao, L., Weng, W., Zhou, Q., Wang, L., Zhai, X. Zhao, Q., Hu, H., Huang, B., Su, J. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis. PMID:28739641

  8. Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice

    Science.gov (United States)

    Chronic alcohol consumption results in bone loss through increased bone resorption and decreased bone formation. These effects can be reversed by estradiol (E2) supplementation. Soy diets are suggested to have protective effects on bone loss in men and women, as a result of the presence of soy prote...

  9. High-impact exercise in rats prior to and during suspension can prevent bone loss.

    Science.gov (United States)

    Yanagihara, G R; Paiva, A G; Gasparini, G A; Macedo, A P; Frighetto, P D; Volpon, J B; Shimano, A C

    2016-03-01

    High-impact exercise has been considered an important method for treating bone loss in osteopenic experimental models. In this study, we investigated the effects of osteopenia caused by inactivity in femora and tibiae of rats subjected to jump training using the rat tail suspension model. Eight-week-old female Wistar rats were divided into five groups (n=10 each group): jump training for 2 weeks before suspension and training during 3 weeks of suspension; jump training for 2 weeks before suspension; jump training only during suspension; suspension without any training; and a control group. The exercise protocol consisted of 20 jumps/day, 5 days/week, with a jump height of 40 cm. The bone mineral density of the femora and tibiae was measured by double energy X-ray absorptiometry and the same bones were evaluated by mechanical tests. Bone microarchitecture was evaluated by scanning electron microscopy. One-way ANOVA was used to compare groups. Significance was determined as Pbone mineral density, mechanical properties and bone microarchitecture, the beneficial effects were greater in the bones of animals subjected to pre-suspension training and subsequently to training during suspension, compared with the bones of animals subjected to pre-suspension training or to training during suspension. Our results indicate that a period of high impact exercise prior to tail suspension in rats can prevent the installation of osteopenia if there is also training during the tail suspension.

  10. Feeding blueberry diets during early development is sufficient to prevent senescence of osteoblasts and bone loss in adulthood

    Science.gov (United States)

    Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we show that feeding a high quality diet supplemented...

  11. Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats

    Science.gov (United States)

    Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we show that feeding a high quality diet supplemented...

  12. Total glucosides of paeony prevents juxta-articular bone loss in experimental arthritis.

    Science.gov (United States)

    Wei, Chen Chao; You, Fan Tian; Mei, Li Yu; Jian, Sun; Qiang, Chen Yong

    2013-07-21

    Total glucosides of paeony (TGP) is a biologically active compound extracted from Paeony root. TGP has been used in rheumatoid arthritis therapy for many years. However, the mechanism by which TGP prevents bone loss has been less explored. TGP was orally administered for 3 months to New Zealand rabbits with antigen-induced arthritis (AIA). Digital x-ray knee images and bone mineral density (BMD) measurements of the subchondral knee bone were performed before sacrifice. Chondrocytes were observed using transmission electron microscopy (TEM). Histological analysis and mRNA expression of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) were evaluated in joint tissues. The BMD value in TGP rabbits was significantly higher compared with that seen in the AIA model rabbits. In addition, the subchondral bone plate was almost completely preserved by TGP treatment, while there was a decrease in bone plate integrity in AIA rabbits. There was less damage to the chondrocytes of the TGP treated group. Immunohistochemical examination of the TGP group showed that a higher percentage of TGP treated chondrocytes expressed OPG as compared to the chondrocytes isolated from AIA treated animals. In contrast, RANKL expression was significantly decreased in the TGP treated group compared to the AIA group. In support of the immunohistochemistry data, the expression of RANKL mRNA was decreased and OPG mRNA expression was enhanced in the TGP group when compared to that of the AIA model group. These results reveal that TGP suppresses juxta-articular osteoporosis and prevents subchondral bone loss. The decreased RANKL and increased OPG expression seen in TGP treated animals could explain how administration of TGP maintains higher BMD.

  13. Ampelopsis brevipedunculata Extract Prevents Bone Loss by Inhibiting Osteoclastogenesis in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Ju-Young Kim

    2014-11-01

    Full Text Available Osteoclasts play a critical role in bone resorbing disorders such as osteoporosis, periodontitis, and rheumatoid arthritis. Therefore, discovery of agents capable of suppressing osteoclast differentiation may aid the development of a therapeutic access for the treatment of pathological bone loss. Ampelopsis brevipedunculata has been used as herbal folk medicine to treat liver diseases and inflammation in Asia. However, its effects on osteoclast differentiation are unknown. We were aimed to investigate the anti-osteoclastogenic activity in vitro and in vivo and to elucidate the underlying mechanism of Ampelopsis brevipedunculata extract (ABE. In this study, ABE inhibited receptor activator of NF-κB ligand (RANKL-induced osteoclast differentiation, the formation of filamentous actin rings and the bone resorbing activity of mature osteoclasts. ABE inhibited RANKL-induced p38 and IκB phosphorylation and IκB degradation. Also, ABE suppressed the mRNA and protein expression of nuclear factor of activated T cells c1 (NFATc1 and c-Fos, and the mRNA expression of genes required for cell fusion and bone resorption, such as osteoclast-associated receptor (OSCAR, tartrate resistant acid phosphatase (TRAP, cathepsin K, dendritic cell-specific transmembrane protein (DC-STAMP, β3-integrin and osteoclast stimulatory transmembrane protein (OC-STAMP. Furthermore, results of micro-CT and histologic analysis indicated that ABE remarkably prevented lipopolysaccharide (LPS-induced bone erosion. These results demonstrate that ABE prevents LPS-induced bone erosion through inhibition of osteoclast differentiation and function, suggesting the promise of ABE as a potential cure for various osteoclast-associated bone diseases.

  14. Dried Root of Rehmannia glutinosa Prevents Bone Loss in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Dong Wook Lim

    2013-05-01

    Full Text Available Dried root of Rehmannia glutinosa is a kidney-tonifying herbal medicine with a long history of safe use in traditional folk medicine for the treatment of joint diseases. This study was conducted to investigate prevention of bone loss by a standardized dried root of R. glutinosa in an ovariectomized (OVX rat model of osteoporosis. The OVX groups were divided into five groups treated with distilled water, 17β-estradiol (E2 10 µg/kg, once daily, i.p and dried root of R. glutinosa extracts (DRGE 30, 100, and 300 mg/kg, twice daily, p.o for eight weeks. We measured the body, organs, and uterus weights, and femur and lumbar vertebrae bone mineral density (BMD, serum alkaline phosphatase (ALP, estradiol levels. The treatments with DRGE 300 mg/kg significantly inhibited BMD decrease in the femur and lumbar (17.5% and 16.4%, p < 0.05, respectively by OVX without affecting the body, organs, and uterus weights. Also, serum ALP level in the DRGE 300 mg/kg treated group was significantly decreased, but the estradiol level did not change in serum of the DRGE 300 mg/kg treated group. These results show that DRGE is able to prevent OVX-induced bone loss without influencing hormones such as estrogen.

  15. Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo.

    Science.gov (United States)

    Zhai, Z J; Li, H W; Liu, G W; Qu, X H; Tian, B; Yan, W; Lin, Z; Tang, T T; Qin, A; Dai, K R

    2014-02-01

    Osteoclasts play a pivotal role in diseases such as osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. Here, we examined changes in osteoclastogenesis and LPS-induced osteolysis in response to andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata. Effects of AP on osteoclast differentiation and bone resorption were measured in vitro. Western blots and RT-PCR techniques were used to examine the underlying molecular mechanisms. The bone protective activity of AP in vivo was assessed in a mouse model of osteolysis. AP concentration-dependently suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro and reduced the expression of osteoclast-specific markers, including tartrate-resistant acid phosphatase, calcitonin receptors and cathepsin K. Further molecular analysis revealed that AP impaired RANKL-induced NF-κB signalling by inhibiting the phosphorylation of TGF-β-activated kinase 1, suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the nuclear translocation of the NF-κB p65 subunit. AP also inhibited the ERK/MAPK signalling pathway without affecting p38 or JNK signalling. AP suppressed RANKL-induced osteoclastogenesis through attenuating NF-κB and ERK/MAPK signalling pathways in vitro, thus preventing bone loss in vivo. These data indicated that AP is a promising natural compound for the treatment of osteoclast-related bone diseases. © 2013 The British Pharmacological Society.

  16. Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

    Science.gov (United States)

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

  17. Myricetin Prevents Alveolar Bone Loss in an Experimental Ovariectomized Mouse Model of Periodontitis

    Directory of Open Access Journals (Sweden)

    Jialiang Huang

    2016-03-01

    Full Text Available Periodontitis is a common chronic inflammatory disease, which leads to alveolar bone resorption. Healthy and functional alveolar bone, which can support the teeth and enable their movement, is very important for orthodontic treatment. Myricetin inhibited osteoclastogenesis by suppressing the expression of some genes, signaling pathways, and cytokines. This study aimed to investigate the effects of myricetin on alveolar bone loss in an ovariectomized (OVX mouse model of periodontitis as well as in vitro osteoclast formation and bone resorption. Twenty-four healthy eight-week-old C57BL/J6 female mice were assigned randomly to four groups: phosphate-buffered saline (PBS control (sham OVX + ligature + PBS (vehicle, and OVX + ligature + low or high (2 or 5 mg∙kg−1∙day−1, respectively doses of myricetin. Myricetin or PBS was injected intraperitoneally (i.p. every other day for 30 days. The maxillae were collected and subjected to further examination, including micro-computed tomography (micro-CT, hematoxylin and eosin (H&E staining, and tartrate-resistant acid phosphatase (TRAP staining; a resorption pit assay was also performed in vitro to evaluate the effects of myricetin on receptor activator of nuclear factor κ-B ligand (RANKL-induced osteoclastogenesis. Myricetin, at both high and low doses, prevented alveolar bone resorption and increased alveolar crest height in the mouse model and inhibited osteoclast formation and bone resorption in vitro. However, myricetin was more effective at high dose than at low dose. Our study demonstrated that myricetin had a positive effect on alveolar bone resorption in an OVX mouse model of periodontitis and, therefore, may be a potential agent for the treatment of periodontitis and osteoporosis.

  18. 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.

  19. Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model.

    Science.gov (United States)

    Britton, Robert A; Irwin, Regina; Quach, Darin; Schaefer, Laura; Zhang, Jing; Lee, Taehyung; Parameswaran, Narayanan; McCabe, Laura R

    2014-11-01

    Estrogen deficiency is a major risk factor for osteoporosis that is associated with bone inflammation and resorption. Half of women over the age of 50 will experience an osteoporosis related fracture in their lifetime, thus novel therapies are needed to combat post-menopausal bone loss. Recent studies suggest an important role for gut-bone signaling pathways and the microbiota in regulating bone health. Given that the bacterium Lactobacillus reuteri ATCC PTA 6475 (L. reuteri) secretes beneficial immunomodulatory factors, we examined if this candidate probiotic could reduce bone loss associated with estrogen deficiency in an ovariectomized (Ovx) mouse menopausal model. Strikingly, L. reuteri treatment significantly protected Ovx mice from bone loss. Osteoclast bone resorption markers and activators (Trap5 and RANKL) as well as osteoclastogenesis are significantly decreased in L. reuteri-treated mice. Consistent with this, L. reuteri suppressed Ovx-induced increases in bone marrow CD4+ T-lymphocytes (which promote osteoclastogenesis) and directly suppressed osteoclastogenesis in vitro. We also identified that L. reuteri treatment modifies microbial communities in the Ovx mouse gut. Together, our studies demonstrate that L. reuteri treatment suppresses bone resorption and loss associated with estrogen deficiency. Thus, L. reuteri treatment may be a straightforward and cost-effective approach to reduce post-menopausal bone loss. © 2014 Wiley Periodicals, Inc.

  20. Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: The BATMAN Trial.

    Science.gov (United States)

    Lomax, Anna J; Yee Yap, Saw; White, Karen; Beith, Jane; Abdi, Ehtesham; Broad, Adam; Sewak, Sanjeev; Lee, Chooi; Sambrook, Philip; Pocock, Nicholas; Henry, Margaret J; Yeow, Elaine G; Bell, Richard

    2013-12-01

    Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures. In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D. All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm. At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate. There was a significant drop in lumbar spine (-5.4%) and hip (-4.5%) mean BMD, in the normal BMD group, none of whom received alendronate. Fracture data will be presented. In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic.

  1. Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats.

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    Full Text Available Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied.In this report, we show that feeding a high quality diet supplemented with blueberries (BB to pre-pubertal rats throughout development or only between postnatal day 20 (PND20 and PND34 prevented ovariectomy (OVX-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation.These results indicate: 1 a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2 the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.

  2. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group

    DEFF Research Database (Denmark)

    Hosking, D; Chilvers, C E; Christiansen, C

    1998-01-01

    increases in bone mineral density. Alendronate did not increase bone mineral density of the forearm, but it slowed the loss. The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate. Alendronate was well tolerated, with a safety profile similar...... to that of placebo or estrogen-progestin. CONCLUSIONS: Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin.......BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS...

  3. Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss

    International Nuclear Information System (INIS)

    Cheon, Yoon-Hee; Kim, Ju-Young; Baek, Jong Min; Ahn, Sung-Jun; So, Hong-Seob; Oh, Jaemin

    2016-01-01

    Niclosamide (5-chloro-salicyl-(2-chloro-4-nitro) anilide) is an oral anthelmintic drug used for treating intestinal infection of most tapeworms. Recently, niclosamide was shown to have considerable efficacy against some tumor cell lines, including colorectal, prostate, and breast cancers, and acute myelogenous leukemia. Specifically, the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 (STAT3), which is associated with osteoclast differentiation and function. In this study, we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was inhibited by niclosamide, due to inhibition of serine–threonine protein kinase (Akt) phosphorylation, inhibitor of nuclear factor-kappaB (IκB), and STAT3 serine 727 . Niclosamide decreased the expression of the major transcription factors c-Fos and NFATc1, and thereafter abrogated the mRNA expression of osteoclast-specific genes, including TRAP, OSCAR, αv/β3 integrin (integrin αv, integrin β3), and cathepsin K (CtsK). In an in vivo model, niclosamide prevented lipopolysaccharide-induced bone loss by diminishing osteoclast activity. Taken together, our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • We first investigated the anti-osteoclastogenic effects of niclosamide in vitro and in vivo. • Niclosamide impairs the activation of the Akt-IκB-STAT3 ser 727 signaling axis. • Niclosamide acts a negative regulator of actin ring formation during osteoclast differentiation. • Niclosamide suppresses LPS-induced bone loss in vivo. • Niclosamide deserves new evaluation as a potential treatment target in various bone diseases.

  4. Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Yoon-Hee [Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Ju-Young [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Baek, Jong Min; Ahn, Sung-Jun [Department of Anatomy, School of Medicine, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Oh, Jaemin, E-mail: jmoh@wku.ac.kr [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Department of Anatomy, School of Medicine, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2016-02-05

    Niclosamide (5-chloro-salicyl-(2-chloro-4-nitro) anilide) is an oral anthelmintic drug used for treating intestinal infection of most tapeworms. Recently, niclosamide was shown to have considerable efficacy against some tumor cell lines, including colorectal, prostate, and breast cancers, and acute myelogenous leukemia. Specifically, the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 (STAT3), which is associated with osteoclast differentiation and function. In this study, we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was inhibited by niclosamide, due to inhibition of serine–threonine protein kinase (Akt) phosphorylation, inhibitor of nuclear factor-kappaB (IκB), and STAT3 serine{sup 727}. Niclosamide decreased the expression of the major transcription factors c-Fos and NFATc1, and thereafter abrogated the mRNA expression of osteoclast-specific genes, including TRAP, OSCAR, αv/β3 integrin (integrin αv, integrin β3), and cathepsin K (CtsK). In an in vivo model, niclosamide prevented lipopolysaccharide-induced bone loss by diminishing osteoclast activity. Taken together, our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • We first investigated the anti-osteoclastogenic effects of niclosamide in vitro and in vivo. • Niclosamide impairs the activation of the Akt-IκB-STAT3 ser{sup 727} signaling axis. • Niclosamide acts a negative regulator of actin ring formation during osteoclast differentiation. • Niclosamide suppresses LPS-induced bone loss in vivo. • Niclosamide deserves new evaluation as a potential treatment target in various bone diseases.

  5. GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

    DEFF Research Database (Denmark)

    Iepsen, Eva Pers Winning; Lundgren, Julie Rehné; Hartmann, Bolette

    2015-01-01

    bone mass reductions. DESIGN: Randomized control study. SETTING: Out-patient research hospital clinic. PARTICIPANTS: Thirty-seven healthy obese women. BMI 34±0.5 kg/m(2), age 46±2 years. INTERVENTION: After a low-calorie diet-induced 12% weight loss, participants were randomized to treatment......CONTEXT: Recent studies indicate that glucagon-like peptide 1 (GLP-1) regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. OBJECTIVE: To investigate the role of GLP-1 RAs on bone formation and weight loss induced...... markers (CTX-1 and P1NP) were investigated before, after weight loss and after 52 weeks weight maintenance. Primary end points: Change in BMC and bone markers after 52 weeks weight maintenance with or without GLP-1 RA treatment. RESULTS: Total, pelvic and arm-leg BMC decreased during weight maintenance...

  6. Low doses of estradiol in combination with gestodene to prevent early postmenopausal bone loss.

    Science.gov (United States)

    Bjarnason, N H; Byrjalsen, I; Hassager, C; Haarbo, J; Christiansen, C

    2000-09-01

    Our purpose was to study combinations of estradiol and gestodene for prevention of bone loss in early postmenopausal women. We randomly assigned 278 healthy, early postmenopausal women to receive either 2 mg 17beta-estradiol sequentially combined with 25 microg gestodene (group 2/25s), 2 mg estradiol sequentially combined with 50 microg gestodene (group 2/50s), 1 mg estradiol sequentially combined with 25 microg gestodene (group 1/25s), 1 mg estradiol continuously combined with 25 mg gestodene (group 1/25c), or placebo. After 3 years the changes in bone mineral density of the spine were as follows (mean +/- SEM): group 2/25s, 7. 41% +/- 0.72%; group 2/50s, 8.53% +/- 0.90%; group 1.25s, 6.67% +/- 0.88%; group 1/25c, 4.44% +/- 0.59%; and placebo group, -2.03% +/- 0. 64%. The changes in bone mineral density were mirrored in the biochemical bone markers. The average responses for the urinary C-terminal telopeptide fragments of type I collagen corrected for creatinine excretion were as follows (mean of baseline +/- SEM): group 2/25s, -68.8% +/- 0.03%; group 2/50s, -72.8% +/- 0.02%; group 1/25s, -60.7% +/- 0.03%; group 1/25c, -52.28% +/- 0.04%; and placebo group, 6.5% +/- 0.09%. Beneficial lipid effects were found in all active groups. The decreases in low-density lipoprotein were as follows (mean +/- SEM): group 2/25s, -13.7% +/- 3.0%; group 2/50s, -14.6% +/- 3.2%; group 1/25s, -9.28% +/- 2.2%; group 1/25c, -9.92% +/- 2.4%; and placebo group, 1.53% +/- 1.9%. These results demonstrate that estradiol therapy with 1 mg estradiol is fully protective against early postmenopausal bone loss.

  7. Probiotic Lactobacillus rhamnosus GG prevents alveolar bone loss in a mouse model of experimental periodontitis.

    Science.gov (United States)

    Gatej, Simona M; Marino, Victor; Bright, Richard; Fitzsimmons, Tracy R; Gully, Neville; Zilm, Peter; Gibson, Rachel J; Edwards, Suzanne; Bartold, Peter M

    2018-02-01

    This study investigated the role of Lactobacillus rhamnosus GG (LGG) on bone loss and local and systemic inflammation in an in vivo mouse model of experimental periodontitis (PD). Experimental PD was induced in mice by oral inoculation with Porphyromonas gingivalis and Fusobacterium nucleatum over a period of 44 days. The probiotic LGG was administered via oral inoculation or oral gavage prior to, and during disease induction. The antimicrobial activity of LGG on the inoculum was also tested. Alveolar bone levels and gingival tissue changes were assessed using in vivo microcomputed tomography and histological analysis. Serum levels of mouse homologues for IL-8 were measured using multiplex assays. Pre-treatment with probiotics either via oral gavage or via oral inoculation significantly reduced bone loss (p Lactobacillus rhamnosus GG effectively suppresses bone loss in a mouse model of induced PD irrespective of the mode of administration. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Water extract of Rumex crispus prevents bone loss by inhibiting osteoclastogenesis and inducing osteoblast mineralization.

    Science.gov (United States)

    Shim, Ki-Shuk; Lee, Bohyoung; Ma, Jin Yeul

    2017-10-26

    Rumex crispus root has traditionally been used in Asian medicine for the treatment of hemorrhage and dermatolosis. The aim of this study was to explore the pharmaceutical effects of water extract of Rumex crispus (WERC) on osteoblast and osteoclast differentiation. We also studied the effect of WERC on the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced trabecular bone destruction mice model. High performance liquid chromatography analysis was used to identify three compounds (emodin, chrysophanol, and physcion) of WERC. The in vivo effect of WERC was examined using an administration of WERC or vehicle on the ICR mice with bone loss induced by intraperitoneal RANKL injection on day 0 and 1. All mice were sacrificed by cervical dislocation at day 7 and the femurs of mice were isolated for soft X-ray and Micro-CT analysis. The in vitro effect of WERC on osteoblast mineralization or osteoclast differentiation was examined by alizarin red S staining or by tartrate-resistant acid phosphatase staining and assay. To determine the transcription level of osteoblast or osteoclast-specific genes, real-time quantitative polymerase chain reaction was used. Western blot analysis was performed to study the effect of WERC on mitogen-activated protein kinases (MAPK) or nuclear factor-κB (NF-κB) signaling molecules. The presence of three compounds in WERC was determined. WERC significantly suppressed RANKL-induced trabecular bone loss by preventing microstructural deterioration. In vitro, WERC increased osteoblast mineralization by enhancing the transcription of runt-related transcription factor 2 and its transcriptional coactivators, and by stimulating extracellular signal-regulated kinase phosphorylation. Furthermore, WERC significantly inhibited osteoclast differentiation by suppressing the activation of the RANKL signalings (MAPK and NF-κB) and the increasing inhibitory factors of nuclear factor of activated T cells cytoplasmic 1. This study showed that

  9. Iguratimod prevents ovariectomy‑induced bone loss and suppresses osteoclastogenesis via inhibition of peroxisome proliferator‑activated receptor‑γ.

    Science.gov (United States)

    Wu, Ying-Xing; Sun, Yue; Ye, Ya-Ping; Zhang, Peng; Guo, Jia-Chao; Huang, Jun-Ming; Jing, Xing-Zhi; Xiang, Wei; Yu, Shi-Ying; Guo, Feng-Jing

    2017-12-01

    Iguratimod is known for its anti‑inflammatory activities and therapeutic effects in patients with rheumatoid arthritis. It has previously been demonstrated that iguratimod attenuates bone destruction and osteoclast formation in the Walker 256 rat mammary gland carcinoma cell‑induced bone cancer pain model. Therefore, it was hypothesized that iguratimod may additionally exhibit therapeutic effects on benign osteoclast‑associated diseases including postmenopausal osteoporosis. In the present study, ovariectomized mice were used to investigate the effects of iguratimod in vivo. Bone marrow mononuclear cells were cultured to detect the effects of iguratimod on receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclastogenesis in vitro and the molecular mechanisms involved. It was demonstrated that iguratimod may prevent ovariectomy‑induced bone loss by suppressing osteoclast activity in vivo. Consistently, iguratimod may inhibit RANKL‑induced osteoclastogenesis and bone resorption in primary bone marrow mononuclear cells. At the molecular level, peroxisome proliferator‑activated receptor‑γ (PPAR‑γ)/c‑Fos pathway, which is essential in RANKL‑induced osteoclast differentiation, was suppressed by iguratimod. Subsequently, iguratimod decreased the expression of nuclear factor of activated T cells c1 and downstream osteoclast marker genes. The results of the present study demonstrated that iguratimod may inhibit ovariectomy‑induced bone loss and osteoclastogenesis by modulating RANKL signaling. Therefore, iguratimod may act as a novel therapeutic to prevent postmenopausal osteoporosis.

  10. Olive oil and vitamin D synergistically prevent bone loss in mice.

    Directory of Open Access Journals (Sweden)

    Camille Tagliaferri

    Full Text Available As the Mediterranean diet (and particularly olive oil has been associated with bone health, we investigated the impact of extra virgin oil as a source of polyphenols on bone metabolism. In that purpose sham-operated (SH or ovariectomized (OVX mice were subjected to refined or virgin olive oil. Two supplementary OVX groups were given either refined or virgin olive oil fortified with vitamin D3, to assess the possible synergistic effects with another liposoluble nutrient. After 30 days of exposure, bone mineral density and gene expression were evaluated. Consistent with previous data, ovariectomy was associated with increased bone turnover and led to impaired bone mass and micro-architecture. The expression of oxidative stress markers were enhanced as well. Virgin olive oil fortified with vitamin D3 prevented such changes in terms of both bone remodeling and bone mineral density. The expression of inflammation and oxidative stress mRNA was also lower in this group. Overall, our data suggest a protective impact of virgin olive oil as a source of polyphenols in addition to vitamin D3 on bone metabolism through improvement of oxidative stress and inflammation.

  11. Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss.

    Science.gov (United States)

    Cheon, Yoon-Hee; Kim, Ju-Young; Baek, Jong Min; Ahn, Sung-Jun; So, Hong-Seob; Oh, Jaemin

    2016-02-05

    Niclosamide (5-chloro-salicyl-(2-chloro-4-nitro) anilide) is an oral anthelmintic drug used for treating intestinal infection of most tapeworms. Recently, niclosamide was shown to have considerable efficacy against some tumor cell lines, including colorectal, prostate, and breast cancers, and acute myelogenous leukemia. Specifically, the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 (STAT3), which is associated with osteoclast differentiation and function. In this study, we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was inhibited by niclosamide, due to inhibition of serine-threonine protein kinase (Akt) phosphorylation, inhibitor of nuclear factor-kappaB (IκB), and STAT3 serine(727). Niclosamide decreased the expression of the major transcription factors c-Fos and NFATc1, and thereafter abrogated the mRNA expression of osteoclast-specific genes, including TRAP, OSCAR, αv/β3 integrin (integrin αv, integrin β3), and cathepsin K (CtsK). In an in vivo model, niclosamide prevented lipopolysaccharide-induced bone loss by diminishing osteoclast activity. Taken together, our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast-related diseases such as osteoporosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Naringin prevents bone loss in a rat model of type 1 Diabetes mellitus.

    Science.gov (United States)

    Rivoira, M; Rodríguez, V; Picotto, G; Battaglino, R; Tolosa de Talamoni, N

    2018-01-01

    The aim of this work was to know whether naringin (NA) could prevent the bone complications in a model of streptozotocin (STZ) induced diabetes. Rats were divided in: 1) controls, 2) STZ-rats, 3) STZ-rats treated with 40 mg NA/kg, and 4) STZ-rats treated with 80 mg NA/kg. BMD and BMC were performed by DEXA. Bone histomorphometry and histology as well as TRAP staining were done in tibia. Osteocalcin (OCN) was determined in bone and serum. Glutathione content and SOD and catalase activities were assayed in bone marrow from femur. The data showed that NA80 increased the BMD and BMC from the long bones of STZ-rats. Both NA40 and NA80 normalized the trabecular number and the trabecular separations. An increase in the number of adipocytes and TRAP(+) cells in tibia from STZ-rats was blocked by NA. NA40 treatment increased the number of OCN(+) cells, but only the NA80 treatment allowed to reach the control values. NA normalized the SOD and catalase activities in bone marrow of femur from STZ-rats. In conclusion, NA avoids alterations in the physical properties and microstructure of bone from STZ-rats probably by stimulation of osteoblastogenesis, inhibition of the osteoclastogenesis and adipogenesis via blocking the oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro.

    Science.gov (United States)

    Spilmont, Mélanie; Léotoing, Laurent; Davicco, Marie-Jeanne; Lebecque, Patrice; Miot-Noirault, Elisabeth; Pilet, Paul; Rios, Laurent; Wittrant, Yohann; Coxam, Véronique

    2015-11-11

    The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE) could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX) C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (-31.9%; p < 0.001 vs. OVX mice) and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP) activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.

  14. Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro

    Directory of Open Access Journals (Sweden)

    Mélanie Spilmont

    2015-11-01

    Full Text Available The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (−31.9%; p < 0.001 vs. OVX mice and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.

  15. Non-pharmacological treatment and prevention of bone loss after spinal cord injury: a systematic review

    DEFF Research Database (Denmark)

    Biering-Sørensen, F; Hansen, B; Lee, B S B

    2009-01-01

    OBJECTIVE: Review the literature on non-pharmacological prevention and treatment of osteoporosis after spinal cord injury (SCI). METHODS: PubMed, EMBASE and the Cochrane Controlled Trials Register were searched. All identified papers were read by title, abstract and full-length article when...... and outcome measures that could be improved. Five studies on weight-bearing early post-injury are conflicting, but standing or walking may help retain bone mineral. In the chronic phase, there was no effect of weight bearing (12 studies). One study found that an early commencement of sports after SCI improved...... bone mineral, and the longer the period of athletic career, the higher the (leg) bone mineral. Early after SCI, there may be some effects of electrical stimulation (ES) (five studies). Chronic-phase ES studies vary (14 studies, including mixed periods after injury), but improvement is seen with longer...

  16. Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid.

    Science.gov (United States)

    Calomme, M; Geusens, P; Demeester, N; Behets, G J; D'Haese, P; Sindambiwe, J B; Van Hoof, V; Vanden Berghe, D

    2006-04-01

    Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with ch-OSA over 30 weeks (OVX1, n = 20; 1 mg Si/kg body weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and the 24-hour urinary Si excretion of supplemented OVX rats was significantly higher compared to sham and OVX controls. Supplementation with ch-OSA significantly but partially reversed the decrease in Ca excretion, which was observed after OVX. The increase in bone turnover in OVX rats tended to be reduced by ch-OSA supplementation. ch-OSA supplementation increased significantly the femoral bone mineral content (BMC) in the distal region and total femoral BMC in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was significantly increased at two sites in the distal region in OVX rats supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral density was marginally increased by ch-OSA supplementation. In conclusion, ch-OSA supplementation partially prevents femoral bone loss in the aged OVX rat model.

  17. Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Wenxin; Yan, Xingrong; Du, Huicong; Cui, Jihong; Li, Liwen, E-mail: liven@nwu.edu.cn; Chen, Fulin, E-mail: chenfl@nwu.edu.cn

    2013-05-03

    Highlights: •A GST-FSH fusion protein was successfully expressed in E. coli. •Immunization with GST-FSH antigen can raise high-titer anti-FSH polyclonal sera. •Anti-FSH polyclonal sera can neutralize osteoclastogenic effect of FSH in vitro. •FSH immunization can prevent bone loss in a rat osteoporosis model. -- Abstract: Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal α and β estrogen receptor null mice were only mildly osteopenic, and mice with either receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSHβ fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSHβ antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women.

  18. Biologicals and bone loss

    NARCIS (Netherlands)

    Krieckaert, C.L.M.; Lems, W.F.

    2012-01-01

    Inflammatory joint diseases are associated with extra-articular side effects including bone involvement.There is an increased risk of osteoporotic fractures. The pathogeneses of local and generalized bone loss share a common pathway. Early and active rheumatoid arthritis is associated with

  19. Menopause and Bone Loss

    Science.gov (United States)

    ... calcium supplement if necessary. • Vitamin D. Your body needs vitamin D to absorb calcium and move it into ... bone density test? • Should I take calcium and vitamin D supplements? How much do I need? • Do I need medication for my bone loss? • ...

  20. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

    Directory of Open Access Journals (Sweden)

    Anne-Priscille Trouvin

    2010-11-01

    Full Text Available Anne-Priscille Trouvin, Vincent GoëbDepartment of Rheumatology, Rouen University Hospital, Rouen, FranceAbstract: Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG and receptor activator for nuclear factor-κB (RANK ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss and ensure a normal bone turnover. In this review, the RANK/RANKL/OPG pathway is described. The multiple interactions of various factors (hormones, cytokines, growth factors, and vitamins with the OPG/RANK/RANKL pathway are also commented on. Finally, the effects of denosumab, a human monoclonal antibody that binds to RANKL and thereby inhibits the activation of osteoclasts, and of strontium ranelate are also described. Indeed, these two new drugs afford appreciable assistance in daily care practice, helping to prevent bone loss in patients with osteoporosis.Keywords: osteoprotegerin, OPG, RANK, RANKL, denosumab, strontium ranelate, osteoporosis

  1. Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model.

    Science.gov (United States)

    Geng, Wenxin; Yan, Xingrong; Du, Huicong; Cui, Jihong; Li, Liwen; Chen, Fulin

    2013-05-03

    Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal α and β estrogen receptor null mice were only mildly osteopenic, and mice with either receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSHβ fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSHβ antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Evaluation in a Dog Model of Three Antimicrobial Glassy Coatings: Prevention of Bone Loss around Implants and Microbial Assessments.

    Directory of Open Access Journals (Sweden)

    Roberto López-Píriz

    Full Text Available The aim of the present study is to evaluate, in a ligature-induced peri-implantitis model, the efficacy of three antimicrobial glassy coatings in the prevention of biofilm formation, intrasulcular bacterial growth and the resulting peri-implant bone loss.Mandibular premolars were bilaterally extracted from five beagle dogs. Four dental implants were inserted on each hemiarch. Eight weeks after, one control zirconia abutment and three with different bactericidal coatings (G1n-Ag, ZnO35, G3 were connected. After a plaque control period, bacterial accumulation was allowed and biofilm formation on abutments was observed by Scanning Electron Microscopy (SEM. Peri-implantitis was induced by cotton ligatures. Microbial samples and peri-implant crestal bone levels of all implant sites were obtained before, during and after the breakdown period.During experimental induce peri-implantitis: colony forming units counts from intrasulcular microbial samples at implants with G1n-Ag coated abutment remained close to the basal inoculum; G3 and ZnO35 coatings showed similar low counts; and anaerobic bacterias counts at control abutments exhibited a logarithmic increase by more than 2. Bone loss during passive breakdown period was no statistically significant. Additional bone loss occurred during ligature-induce breakdown: 0.71 (SD 0.48 at G3 coating, 0.57 (SD 0.36 at ZnO35 coating, 0.74 (SD 0.47 at G1n-Ag coating, and 1.29 (SD 0.45 at control abutments; and statistically significant differences (p<0.001 were found. The lowest bone loss at the end of the experiment was exhibited by implants dressing G3 coated abutments (mean 2.1; SD 0.42.Antimicrobial glassy coatings could be a useful tool to ward off, diminish or delay peri-implantitis progression.

  3. A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5.

    Science.gov (United States)

    Xin, Zhi; Jin, Cui; Chao, Liu; Zheng, Zhang; Liehu, Cao; Panpan, Pan; Weizong, Weng; Xiao, Zhai; Qingjie, Zhao; Honggang, Hu; Longjuan, Qin; Xiao, Chen; Jiacan, Su

    2018-01-01

    Post-menopausal osteoporosis (PMOP) is a metabolic bone disorder characterized by low bone mass and micro-architectural deterioration of bone tissue. The over-activated osteoclastogenesis, which plays an important role in osteoporosis, has become an important therapeutic target. M54 was a bioactive derivative of the Chinese traditional herb matrine. We found that M54 could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells and RAW264.7 cells through suppressing NF-κB, PI3K/AKT, and MAPKs pathways activity in vitro , and prevent ovariectomy-induced bone loss in vivo . Our previous study has proved that ribosomal protein S5 (RPS5) was a direct target of M19, based on which M54 was synthesized. Thus we deduced that M54 also targeted RPS5. During osteoclastogenesis, the RPS5 level in RAW264.7 cells was significantly down-regulated while M54 could maintain its level. After RPS5 was silenced, the inhibitory effects of M54 on osteoclastogenesis were partially compromised, indicating that M54 took effects through targeting RPS5. In summary, M54 was a potential clinical medicine for post-menopause osteoporosis treatment, and RPS5 is a possible key protein in PMOP.

  4. A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5

    Directory of Open Access Journals (Sweden)

    Zhi Xin

    2018-01-01

    Full Text Available Post-menopausal osteoporosis (PMOP is a metabolic bone disorder characterized by low bone mass and micro-architectural deterioration of bone tissue. The over-activated osteoclastogenesis, which plays an important role in osteoporosis, has become an important therapeutic target. M54 was a bioactive derivative of the Chinese traditional herb matrine. We found that M54 could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells and RAW264.7 cells through suppressing NF-κB, PI3K/AKT, and MAPKs pathways activity in vitro, and prevent ovariectomy-induced bone loss in vivo. Our previous study has proved that ribosomal protein S5 (RPS5 was a direct target of M19, based on which M54 was synthesized. Thus we deduced that M54 also targeted RPS5. During osteoclastogenesis, the RPS5 level in RAW264.7 cells was significantly down-regulated while M54 could maintain its level. After RPS5 was silenced, the inhibitory effects of M54 on osteoclastogenesis were partially compromised, indicating that M54 took effects through targeting RPS5. In summary, M54 was a potential clinical medicine for post-menopause osteoporosis treatment, and RPS5 is a possible key protein in PMOP.

  5. REV-ERBs agonism suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss partially via FABP4 upregulation.

    Science.gov (United States)

    Song, Chao; Tan, Peng; Zhang, Zheng; Wu, Wei; Dong, Yonghui; Zhao, Liming; Liu, Huiyong; Guan, Hanfeng; Li, Feng

    2018-01-22

    REV-ERBs (REV-ERBα and REV-ERBβ) are transcription repressors and circadian regulators. Previous investigations have shown that REV-ERBs repress the expression of target genes, including MMP9 and CX3CR1, in macrophages. Because MMP9 and CX3CR1 reportedly participate in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, we inferred that REV-ERBs might play a role in osteoclastogenesis. In the present study, we found that the REV-ERBα level decreased significantly during RANKL-induced osteoclast differentiation from primary bone marrow-derived macrophages (BMMs). REV-ERBα knockdown by small interfering RNA in BMMs resulted in the enhanced formation of osteoclasts, whereas REV-ERBβ knockdown showed no effect on osteoclast differentiation. Moreover, the REV-ERB agonist SR9009 inhibited osteoclast differentiation and bone resorption. Intraperitoneal SR9009 administration prevented ovariectomy-induced bone loss; this effect was accompanied by decreased serum RANKL and C-terminal telopeptide of type I collagen levels and increased osteoprotegerin levels. Further investigation revealed that NF-κB and MAPK activation and nuclear factor of activated T cells, cytoplasmic 1, and c-fos expression were suppressed by SR9009. The level of reactive oxygen species was also decreased by SR9009, with NADPH oxidase subunits also being down-regulated. In addition, an expression microarray showed that FABP4, an intracellular lipid-binding protein, was up-regulated by REV-ERB agonism. BMS309403, an inhibitor of FABP4, partially prevented the suppression of osteoclastogenesis by SR9009 through stabilizing phosphorylation of p65. To summarize, our results proved that the REV-ERB agonism inhibited osteoclastogenesis partially via FABP4 up-regulation.-Song, C., Tan, P., Zhang, Z., Wu, W., Dong, Y., Zhao, L., Liu, H., Guan, H., Li, F. REV-ERBs agonism suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss partially via FABP4 upregulation.

  6. Associated among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss

    Science.gov (United States)

    Weight loss reduces co-¬morbidities of obesity but decreases bone mass. Our aims were to determine whether adequate dairy intake could prevent weight loss related bone loss and to evaluate the contribution of energy-related hormones and inflammatory markers to bone metabolism. Overweight and obese w...

  7. Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss.

    Directory of Open Access Journals (Sweden)

    Donatella Granchi

    Full Text Available The extracellular acidic milieu in bones results in activation of osteoclasts (OC and inhibition of osteoblasts (OB causing a net loss of calcium from the skeleton and the deterioration of bone microarchitecture. Alkalinization through supplementation with potassium citrate (K citrate has been proposed to limit the osteopenia progression, even though its pharmacological activity in bone microenvironment is not well defined. We evaluated if K citrate was able to prevent the adverse effects that acidic milieu induces on bone cells. OC and OB were maintained in neutral (pH 7.4 versus acidic (pH 6.9 culture medium, and treated with different K citrate concentrations. We evaluated the OC differentiation at seven days, by counting of multinucleated cells expressing tartrate-resistant acid phosphatase, and the activity of mature OC at 14 days, by quantifying of collagen degradation. To evaluate the effects on OB, we analyzed proliferation, mineralization, and expression of bone-related genes. We found that the low pH increased OC differentiation and activity and decreased OB function. The osteoclastogenesis was also promoted by RANKL concentrations ineffective at pH 7.4. Non-cytotoxic K citrate concentrations were not sufficient to steadily neutralize the acidic medium, but a inhibited the osteoclastogenesis, the collagen degradation, and the expression of genes involved in RANKL-mediated OC differentiation, b enhanced OB proliferation and alkaline phosphatase expression, whereas it did not affect the in vitro mineralization, and c were effective also in OC cultures resistant to alendronate, i.e. the positive control of osteoclastogenesis inhibition. In conclusion, K citrate prevents the increase in OC activity induced by the acidic microenvironment, and the effect does not depend exclusively on its alkalizing capacity. These data provide the biological basis for the use of K citrate in preventing the osteopenia progression resulting from low

  8. Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis.

    Science.gov (United States)

    Bhattarai, Govinda; Poudel, Sher Bahadur; Kook, Sung-Ho; Lee, Jeong-Chae

    2016-01-01

    Resveratrol is an antioxidant and anti-inflammatory polyphenol. Periodontitis is induced by oral pathogens, where a systemic inflammatory response accompanied by oxidative stress is the major event initiating disease. We investigated how resveratrol modulates cellular responses and the mechanisms related to this modulation in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (hGFs). We also explored whether resveratrol protects rats against alveolar bone loss in an experimental periodontitis model. Periodontitis was induced around the first upper molar of the rats by applying ligature infused with LPS. Stimulating hGFs with 5μg/ml LPS augmented the expression of cyclooxygenase-2, matrix metalloproteinase (MMP)-2, MMP-9, and Toll-like receptor-4. LPS treatment also stimulated the production of reactive oxygen species (ROS) and the phosphorylation of several protein kinases in the cells. However, the expression of heme oxygenase-1 (HO-1) and nuclear factor-E2 related factor 2 (Nrf2) was inhibited by the addition of LPS. Resveratrol treatment almost completely inhibited all of these changes in LPS-stimulated cells. Specifically, resveratrol alone augmented HO-1 induction via Nrf2-mediated signaling. Histological and micro-CT analyses revealed that administration of resveratrol (5mg/kg body weight) improved ligature/LPS-mediated alveolar bone loss in rats. Resveratrol also attenuated the production of inflammation-related proteins, the formation of osteoclasts, and the production of circulating ROS in periodontitis rats. Furthermore, resveratrol suppressed LPS-mediated decreases in HO-1 and Nrf2 levels in the inflamed periodontal tissues. Collectively, our findings suggest that resveratrol protects rats from periodontitic tissue damage by inhibiting inflammatory responses and by stimulating antioxidant defense systems. The aims of this study were to investigate how resveratrol modulates cellular responses and the mechanisms related to this modulation in

  9. Bone loss during long term space flight is prevented by the application of a short term impulsive mechanical stimulus

    Science.gov (United States)

    Goodship, A. E.; Cunningham, J. L.; Oganov, V.; Darling, J.; Miles, A. W.; Owen, G. W.

    In long term space flight, the mechanical forces applied to the skeleton are substantially reduced and are altered in character. This reduced skeletal loading results in a reduction in bone mass. Exercise techmques currently used in space can maintain muscle mass but the mechanical stimulus provided by this exercise does not prevent bone loss. By applying an external impulsive load for a short period each day, which is intended to mimic the heel strike transient, to the lower limb of an astronaut during a long term space flight (5 months), this study tests the hypothesis that the bone cells can be activated by an appropriate external mechanical stimulus to maintain bone mass throughout prolonged periods of weightlessness. A mechanical loading device was developed to produce a loading of the os-calcis similar to that observed during the heel strike transient. The device is activated by the astronaut to provide a transient load to the heel of one leg whilst providing an equivalent exercising load to the other leg. During the EUROMIR95 mission on the MIR space station, an astronaut used this device for a short period daily throughout the duration of the mission. Pre- and post-flight measurements of bone mineral density (BMD) of the os-calcis and femoral neck of the astronaut were made to determine the efficacy of the device in preventing loss of bone mineral during the mission. On the os-calcis which received the mechanical stimulus, BMD was maintained throughout the period of the flight, while it was reduced by up to 7% on the os-calcis which received no stimulus. Post-flight, BMD in both the stimulated and non-stimulated os-calcis reduces, the extent of this reduction however is less in the stimulated os-calcis. For the femoral neck, the mechanical Stimulation does not produce a positive effect. On the os-calcis which received the mechanical stimulus, BMD was maintained throughout the period of the flight, while it was reduced by up to 7% on the os-calcis which

  10. Evidence for the prevention of bone loss in elderly and old early non-metastatic breast cancer patients treated with aromatase inhibitors

    DEFF Research Database (Denmark)

    Gunmalm, V.; Jørgensen, N. R.; Abrahamsen, B.

    2017-01-01

    Breast cancer (BC) is the most common cancer amongst women worldwide. Bone health is emerging as an important issue for BC survivors. In this literature study, we focus on agents for preventing bone loss in early non-metastatic estrogen receptor positive BC in treatment with aromatase inhibitors...... (AI) and to assess the evidence for antiresorptive treatment of bone loss in early non-metastatic breast cancer. We included randomized controlled trials (RCT's) comparing: (a) bisphosphonates and control; (b) different bisphosphonates; (c) denosumab and control and (d) bisphosphonates vs. denosumab...... in early non-metastatic BC women in AI treatment. Among antiresorptives, zoledronic acid currently has the highest evidence for prevention of AI associated bone loss in early non-metastatic BC. Data on fracture prevention among all patients, elderly and old is sparse. More randomized controlled studies...

  11. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  12. Inhibition of NADPH oxidases prevents chronic ethanol-induced bone loss in female rats

    Science.gov (United States)

    Previous in vitro data suggest that ethanol (EtOH) activates NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox) in osteoblasts leading to accumulation of reactive oxygen species (ROS). This might be a mechanism underlying inhibition of bone formation and increased bone resorption obse...

  13. Vitamin D supplementation prevents hypocalcemia and cortical bone loss associated with chronic feeding in female mice

    Science.gov (United States)

    Dietary cholecalciferol supplementation alone or combined with calcium has shown great promise in improving bone health, which has been attributed to endocrine actions involved in calcium regulation and/or paracrine/autocrine actions within bone. Indeed, we and others have suggested that dietary su...

  14. Prevention of postmenopausal bone loss - effects of alternative administration forms of estrogens, alternative gestagens and calcium addition

    Energy Technology Data Exchange (ETDEWEB)

    Riis, B.J.; Christiansen, C.

    1987-02-01

    Calcium metabolism was examined in 133 healthy postmenopausal women every three months during two years of treatment with oral or percutaneous 17..beta..-estradiol combined with different doses of calcium supplementation and/or different gestagens. Bone mineral content measured in the forearm (single photon absorptiometry), in the spine and in the total skeleton (dual photon absorptiometry) was unchanged in all estrogen-treated groups during the two years of treatment, and the responses in the groups with and without calcium supplementation and with different gestagens were not significantly different. Furthermore, the responses were independent of route of administration of the estrogen. Biochemical indices of bone turnover (serum alkaline phosphatase and fasting urinary hydroxyproline/creatinine) decreased highly significantly during estrogen treatment (p<0.001) independent of route of administration of the estrogen, of calcium supplementation, and of gestagen agent. We conclude that estrogen treatment independently of route of administration, prevents postmenopausal bone loss. The gestagen agents used here do not affect calcium metabolism, and calcium supplementation has no additive effect to estrogen therapy.

  15. Artesunate inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents LPS-induced bone loss in vivo.

    Science.gov (United States)

    Wei, Cheng-Ming; Liu, Qian; Song, Fang-Ming; Lin, Xi-Xi; Su, Yi-Ji; Xu, Jiake; Huang, Lin; Zong, Shao-Hui; Zhao, Jin-Min

    2018-01-01

    Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL-induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF-κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)-induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL-induced osteoclastogenesis by suppressing the NF-κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases. © 2017 Wiley Periodicals, Inc.

  16. Evidence that increased calcium intake does not prevent early postmenopausal bone loss

    DEFF Research Database (Denmark)

    Hosking, D J; Ross, P D; Thompson, D E

    1998-01-01

    intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose....... In addition to adequate calcium intake, more effective therapy appears to be required when the therapeutic goal is to increase or maintain BMD....

  17. Prevention of Bone Loss after Acute SCI by Zoledronic Acid: Durability, Effect on Bone Strength, and Use of Biomarkers to Guide Therapy

    Science.gov (United States)

    2016-10-01

    Bone Loss after Acute SCI by Zoledronic Acid: Durability, Effect on Bone Strength, and Use of Biomarkers to Guide Therapy 5b. GRANT NUMBER W81XWH-14...duration of its effects and the value of using biomarkers to guide therapy. Data collection ( bone imaging and biomarkers) occurs at baseline and after 3...the durability of response to zoledronic acid and the utility of serum bone markers to guide therapeutic decision making. DXA imaging, CT imaging

  18. B Cell IgD Deletion Prevents Alveolar Bone Loss Following Murine Oral Infection

    Directory of Open Access Journals (Sweden)

    Pamela J. Baker

    2009-01-01

    and CD4+ T cells in immune normal mice compared to IgD deficient mice. These data suggest that IgD is an important mediator of alveolar bone resorption, possibly through antigen-specific coactivation of B cells and CD4+ T cells.

  19. ITI implants with overdentures: a prevention of bone loss in edentulous mandibles?

    DEFF Research Database (Denmark)

    von Wowern, N; Harder, F; Hjørting-Hansen, E

    1990-01-01

    Changes in the bone mineral content (BMC) of edentulous mandibles with osseointegrated ITI implants supporting overdentures were measured in vivo by dual-photon absorptiometry. The BMC measurements were performed 3 weeks postoperatively and at the 2-year follow-up visit. Measurements were made in...

  20. ITI implants with overdentures: a prevention of bone loss in edentulous mandibles?

    DEFF Research Database (Denmark)

    von Wowern, N; Harder, F; Hjørting-Hansen, E

    1990-01-01

    Changes in the bone mineral content (BMC) of edentulous mandibles with osseointegrated ITI implants supporting overdentures were measured in vivo by dual-photon absorptiometry. The BMC measurements were performed 3 weeks postoperatively and at the 2-year follow-up visit. Measurements were made...

  1. Tocilizumab potentially prevents bone loss in patients with anticitrullinated protein antibody-positive rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Yi-Ming Chen

    Full Text Available Rheumatoid arthritis (RA is associated with a high risk of osteoporosis and fracture. Interleukin (IL-6 inhibitors may suppress osteoclast activation. Anticitrullinated protein antibody (ACPA titers are inversely associated with bone mineral density (BMD. However, the differential effect of ACPA on bone turnover marker (BTM and BMD changes after IL-6 inhibition remains unclear. This prospective study recruited patients with active RA with inadequate response to methotrexate or biologics. BMD was measured before and after 2-year tocilizumab (TCZ treatment. Serum osteocalcin, N-terminal propeptide of type I collagen (P1NP, and C-terminal cross-linking telopeptide of type I collagen (CTX levels were assessed at the baseline and after treatment. We enrolled 76 patients with RA (89.5% women, age: 57.2 ± 13.3 years receiving TCZ. The 28-joint disease activity score was negatively correlated with BMD and T-scores of the lumbar spine and bilateral femoral neck. ACPA-positive patients had lower lumbar spine and femoral neck T-scores. After 2-year TCZ treatment, CTX levels significantly decreased (0.32 ± 0.21 vs. 0.26 ± 0.17, p = 0.038. Femoral neck BMD increased significantly (0.71 ± 0.22 vs. 0.69 ± 0.55, p = 0.008. Decreased CTX levels and improved BMD were observed only in ACPA-positive patients. After treatment, femoral neck BMD significantly increased only in patients receiving a glucocorticoid dose of ≥5 mg/day. Two-year TCZ treatment reduced bone resorption and increased femoral BMD in ACPA-positive patients. The net effects of glucocorticoids and IL-6 inhibition on BMD imply that strict inflammation control might affect bone metabolism.

  2. Lipoxin A4 suppresses osteoclastogenesis in RAW264.7 cells and prevents ovariectomy-induced bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Changyu; Guan, Hanfeng; Cai, Cong; Li, Feng, E-mail: lifengmd@hust.edu.cn; Xiao, Jun, E-mail: jun_xiao@hust.edu.cn

    2017-03-15

    Lipoxin A4 (LXA4; 5S, 6R, 15Strihydroxy- 7,9,13-trans-11-eicosatetraenoic acid) is a metabolic product of arachidonic acid under the action of lipoxidase. This lipid molecule plays important roles in several biological functions, especially inflammatory processes. In vivo, LXA4 regulates the inflammatory response through several signaling pathways. Its mechanism suggests that it might have an effect on osteoclastogenesis and bone loss. Using both in vitro and in vivo studies, it was here observed that LXA4 could significantly inhibit the formation and function of osteoclasts and these effects could be blocked by Boc-2, the specific inhibitor of FPR2/ALX (the receptor of LXA4). Meanwhile, LXA4 reduce the amount of ovariectomy-induced bone loss. These protective effects was found to be associated with inhibition of nuclear factor-κB (NF-κB), activator protein-1 (AP-1), PI3K-AKT, and p-38, ERK, and JNK in MAPKs. The expression of the receptor activator of the NF-κB ligand RANKL:osteoprotegerin ratio and serum levels of TNF-α, IL-1β, and IL-6 were decreased by LXA4. Moreover, LXA4 prevented the production of reactive oxygen species (ROS), the expression of osteoclast-specific genes, including tartrate-resistant acid phosphatase (TRAP), cathepsin K (CK), matrix metalloproteinase (MMP)-9, RANK, and osteoclastic related transcription factors of c-Fos, NFATc1 could also be significantly inhibited by LXA4 in a dose-dependent manner. Studies have demonstrated that LXA4 can inhibit the formation and function of osteoclasts through modulation of several pathways both upstream and downstream of RANKL signaling and FPR2/ALX was involved in the procedures. This shows that LXA4 may be used as a new strategy for the treatment of osteoclast-related diseases. - Highlights: • Lipoxin A4 can significantly inhibit the formation and function of osteoclasts. • Several pathways both upstream and downstream of RANKL signaling can be inhibit by Lipoxin A4. • Lipoxin A4 can

  3. Implant-supported overdentures, a prevention of bone loss in edentulous mandibles? A 5-year follow-up study

    DEFF Research Database (Denmark)

    von Wowern, N; Gotfredsen, K

    2001-01-01

    the physiologic age-related mandibular BMC loss, 2) this effect seems to be independent of attachment system and 3) mandibular osteoporosis prior to implant treatment may be a risk factor for bone loss around implants. However, this treatment can be recommended also in osteoporotic persons.......The purpose of this study were to analyse 1) the changes in the bone mineral content (BMC) in mandibles with implant-supported overdentures when compared with the physiologic age-related mandibular BMC loss, 2) whether the BMC changes were different in groups without or with a bar connecting...... the implants and 3) whether the presence of mandibular osteoporosis affects the loss of bone height around the implants. The material consisted of 22 long-term edentulous healthy persons, 18 women and 4 men from 54 to 78 years of age with 1 Astra Tech Dental Implant in both canine regions, connected by a bar...

  4. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group

    DEFF Research Database (Denmark)

    Hosking, D; Chilvers, C E; Christiansen, C

    1998-01-01

    BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS...

  5. Implant-supported overdentures, a prevention of bone loss in edentulous mandibles? A 5-year follow-up study

    DEFF Research Database (Denmark)

    von Wowern, N; Gotfredsen, K

    2001-01-01

    the implants and 3) whether the presence of mandibular osteoporosis affects the loss of bone height around the implants. The material consisted of 22 long-term edentulous healthy persons, 18 women and 4 men from 54 to 78 years of age with 1 Astra Tech Dental Implant in both canine regions, connected by a bar......The purpose of this study were to analyse 1) the changes in the bone mineral content (BMC) in mandibles with implant-supported overdentures when compared with the physiologic age-related mandibular BMC loss, 2) whether the BMC changes were different in groups without or with a bar connecting...... of bone height around implants was measured on periodically identical intraoral radiographs. The fixed parts of the implant-system were stable during the trial in all patients. In conclusion: 1) the increased function after this treatment seems to cause a load-related bone formation which minimizes...

  6. Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment

    Science.gov (United States)

    Deng, Claudia; Wang, Ping; Zhang, Xiangming; Wang, Ya

    2015-04-01

    Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient exercise programs (with less time) to prevent astronauts from muscle atrophy and bone loss are needed. Consider the two types of muscle contraction: exercising forces muscle contraction and prevents microgravity-induced muscle atrophy/bone loss, which is a voluntary response through the motor nervous system; and cold temperature exposure-induced muscle contraction is an involuntary response through the vegetative nervous system, we formed a new hypothesis. The main purpose of this pilot study was to test our hypothesis that exercise at 4 °C is more efficient than at room temperature to prevent microgravity-induced muscle atrophy/bone loss and, consequently reduces physical exercise time. Twenty mice were divided into two groups with or without daily short-term (10 min × 2, at 12 h interval) cold temperature (4 °C) exposure for 30 days. The whole bodyweight, muscle strength and bone density were measured after terminating the experiments. The results from the one-month pilot study support our hypothesis and suggest that it would be reasonable to use more mice, in a microgravity environment and observe for a longer period to obtain a conclusion. We believe that the results from such a study will help to develop efficient exercise, which will finally benefit astronauts' heath and NASA's missions.

  7. What causes bone loss?

    Science.gov (United States)

    ... Paula FJA, Black DM, Rosen CJ. Osteoporosis and bone biology. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, PA: ... HM. Bone development and remodeling. In: Jameson JL, De Groot ...

  8. A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy–induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial

    Science.gov (United States)

    Ofotokun, Ighovwerha; Titanji, Kehmia; Lahiri, Cecile D.; Vunnava, Aswani; Foster, Antonina; Sanford, Sara E.; Sheth, Anandi N.; Lennox, Jeffrey L.; Knezevic, Andrea; Ward, Laura; Easley, Kirk A.; Powers, Philip; Weitzmann, M. Neale

    2016-01-01

    Background. Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among HIV-infected individuals. ART-induced bone loss is most intense within the first 48 weeks of therapy, providing a window for prophylaxis with long-acting antiresorptives. Methods. In a phase 2, double-blind, placebo-controlled trial, we randomized 63 nonosteoporotic, ART-naive adults with HIV initiating ART with atazanavir/ritonavir + tenofovir/emtricitabine to a single zoledronic acid (ZOL) infusion (5 mg) vs placebo to determine the efficacy of ZOL in mitigating ART-induced bone loss. Plasma bone turnover markers and bone mineral density (BMD) were performed at weeks 0, 12, 24, and 48 weeks. Primary outcome was change in C-terminal telopeptide of collagen at 24 weeks. Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. Results. The ZOL arm had a 65% reduction in bone resorption relative to the placebo arm at 24 weeks (0.117 ng/mL vs 0.338 ng/mL; P < .001). This effect of ZOL occurred as early as 12 weeks (73% reduction; P < .001) and persisted through week 48 (57% reduction; P < .001). The ZOL arm had an 8% higher lumbar spine BMD at 12 weeks relative to the placebo arm (P = .003), and remained 11% higher at 24 and 48 weeks. Similar trends were observed in the hip and femoral neck. Conclusions. A single dose of ZOL administered at ART initiation prevented ART-induced bone loss through the first 48 weeks of ART, the period when ART-induced bone loss is most pronounced. Validation of these results in larger multicenter randomized clinical trials is warranted. Clinical Trials Registration. NCT01228318. PMID:27193748

  9. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Spielman, Danièle

    2004-01-01

    OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1...

  10. The Effectiveness of Crataegus orientalis M Bieber. (Hawthorn) Extract Administration in Preventing Alveolar Bone Loss in Rats with Experimental Periodontitis.

    Science.gov (United States)

    Hatipoğlu, Mükerrem; Sağlam, Mehmet; Köseoğlu, Serhat; Köksal, Ekrem; Keleş, Ali; Esen, Hacı Hasan

    2015-01-01

    The purpose of this animal study was to evaluate the effects of hawthorn (Crataeus orientalis M Bieber.) extract on serum oxidative status and alveolar bone loss in experimental periodontitis. Twenty-seven Wistar rats were assigned to one of the following groups: non- ligated+placebo (saline) (NL, n = 9), ligature only+placebo (saline) (LO, n = 9), and ligature and treated with hawthorn extract in saline (H, n = 9) (100 mg/kg orogastrically, once a day for 11 days). Periodontitis was induced by submerging a 4/0 silk ligature in the sulcus of the mandibular right first molars of rats, and the animals were sacrificed after 11 days. Micro-CT examinations were performed for linear and volumetric parameter assessment of alveolar bone. Periodontal tissues were histopathologically examined to assess the differences among the study groups. Levels of serum total antioxidant status (TAS)/total oxidant status (TOS), and oxidative stress index (OSI) were also analyzed. Alveolar bone loss was significantly reduced by hawthorn administration compared to LO group (pHawthorn extract showed inhibitory effect on periodontal inflammation and alveolar bone loss by regulating TAS, TOS and OSI levels in periodontal disease in rats when administered systemically.

  11. Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid

    OpenAIRE

    Calomme, M.; GEUSENS, Piet; Demeester, N.; Behets, G.; D'Haese, P.; Sindambiwe, J.; Van Hoof, V.; VAN DEN BERGHE, David

    2006-01-01

    Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with...

  12. Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats.

    Science.gov (United States)

    Xu, Rongyao; Fu, Zongyun; Liu, Xue; Xiao, Tao; Zhang, Ping; Du, Yifei; Yuan, Hua; Cheng, Jie; Jiang, Hongbing

    2016-11-01

    Estrogen-deficient osteoporosis is an aging-related disease with high morbidity that not only significantly increases a woman's risk of fragility fracture but is also associated with tooth and bone loss in the supporting alveolar bone of the jaw. Emerging evidence suggests that the aging of bone marrow stromal cells (BMSCs) contributes to the development of osteoporosis. In this study, we aimed to investigate the role of the special AT-rich sequence-binding protein 2 (SATB2), a stemness and senescence regulator of craniofacial BMSCs, in rat ovariectomy-induced alveolar osteoporosis. We also sought to determine whether transplantation of SATB2-modified BMSCs could ameliorate estrogen deficient alveolar bone loss. Our data revealed that BMSCs from ovariectomy-induced alveolar bone exhibited typical senescence phenotypes such as diminished stemness and osteogenic capacity, increased expression of senescence or osteoclastic markers and enhanced adipogenic potential. These phenotypic changes are a result of SATB2-mediated senescence dysregulation as evidenced by nuclear γH2AX foci formation. Moreover, overexpression of SATB2 significantly alleviated the senescence of osteoporotic BMSCs in vitro. Importantly, transplantation of SATB2-modified BMSCs significantly attenuated ovariectomy-induced alveolar bone loss in vivo. Together, our results revealed that SATB2 is a critical regulator of alveolar BMSC senescence, and its overexpression decreases these senescent changes both in vitro and in vivo. SATB2-modified BMSC delivery could be a viable and promising therapeutic strategy for alveolar bone loss induced by estrogen-deficient osteoporosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Menopausal bone loss and estrogen replacement.

    Science.gov (United States)

    Meema, S; Meema, H E

    1976-07-01

    Throughout adult life the bone mineral mass of the radius is greater in males than in females. In males, it decreases after 60 years of age, while in females, it decreases earlier, at approximately 50 years, and the loss is greater. At the average age of 67 years, one half of the normal white female population has less than the normal amount of bone in the radius. Premenopausal women over the age of 50 do not show any decline of bone mineral mass, while in postmenopausal women, regardless of age, there is a loss of bone mass related to the number of years after menopause. Castrated women have significantly less bone mass than premenopausal women of the same average age. No decrease in cortical thickness of the radius was found in oophorectomized women treated with estrogens after castration. In a long-term, follow-up study, untreated postmenopausal women (after a natural or an artifical menopause) showed a significant loss of bone mass, while estrogen-treated, postmenopausal women showed no such loss. Estrogen treatment thus appears to prevent postmenopausal bone loss.

  14. Salvia plebeia R.Br. inhibits signal transduction of IL-6 and prevents ovariectomy-induced bone loss by suppressing osteoclastogenesis.

    Science.gov (United States)

    Kim, Mi-Hwa; Jung, Kyungsook; Nam, Ki-Hoan; Jang, Hyun-Jae; Lee, Seung Woong; Kim, Yesol; Park, Chan Sun; Lee, Tae-Hoon; Park, Jee Hun; Choi, Jung Ho; Rho, Mun-Chual; Oh, Hyun-Mee

    2016-12-01

    The interleukin-6 (IL-6) family of cytokines plays a key role in the pathogenesis of rheumatoid arthritis and osteoporosis through the regulation of bone formation and resorption. In this study, it was observed that ethanol extract of Salvia plebeia R.Br. (S.P-EE) inhibited IL-6-induced signaling cascade including phosphorylation of JAK2/STAT3 and ERK. Subsequently, it was examined whether S.P-EE treatment could recover bone loss in ovariectomized (OVX) mice. Indeed, S.P-EE exhibited both preventive and therapeutic effect on OVX-induced bone loss in trabecular microarchitecture along with significant increase in bone mineral density and content. To understand the mechanism of action of S.P-EE in bone metabolism, the effect of S.P-EE on osteoclast differentiation and activity was investigated. S.P-EE significantly inhibited RANKL-induced osteoclast differentiation by suppressing phosphorylation of MAPK and Akt, and expression of NFATc1 and osteoclast marker genes. S.P-EE also inhibited bone-resorbing activity of osteoclasts. Furthermore, isolation and identification of the active compounds which are responsible for the inhibitory effect of S.P-EE on osteoclast differentiation was carried out. Six major flavonoids and plebeiolide A-C were isolated and examined their effects on osteoclast differentiation. Luteolin and hispidulin, and plebeiolide A and C, not B exhibited potent inhibitory activity on RANKL-induced osteoclast formation.

  15. Global Hearing Loss Prevention.

    Science.gov (United States)

    Brown, Clifford Scott; Emmett, Susan D; Robler, Samantha Kleindienst; Tucci, Debara L

    2018-03-07

    Hearing loss is the fourth leading contributor to years lived with a disability worldwide. Most recent estimates indicate that one-half of a billion people suffer from disabling hearing loss worldwide. The social and economic burden is significant. When attributing monetary value to years lived with disability owing to hearing loss, there is greater than $US750 billion lost each year globally. There are numerous contributors to hearing loss, including congenital, infectious, noise exposure, age-related, traumatic, and immune-mediated causes. Understanding the pathophysiology of these factors allows for the development of preventative and treatment strategies specific to the underlying cause. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Prevention of anastrozole-induced bone loss with monthly oral ibandronate during adjuvant aromatase inhibitor therapy for breast cancer.

    Science.gov (United States)

    Lester, James E; Dodwell, David; Purohit, Omprakash P; Gutcher, Sandra A; Ellis, Susan P; Thorpe, Ruth; Horsman, Janet M; Brown, Janet E; Hannon, Rosemary A; Coleman, Robert E

    2008-10-01

    The aromatase inhibitor anastrozole is a highly effective well-tolerated treatment for postmenopausal endocrine-responsive breast cancer. However, its use is associated with accelerated bone loss and an increase in fracture risk. The ARIBON trial is a double-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in women taking anastrozole. BMD was assessed in 131 postmenopausal, surgically treated women with early breast cancer at two U.K. centers. Of these, 50 patients had osteopenia (T score -1.0 to -2.5) at either the hip or lumbar spine. All patients were treated with anastrozole 1 mg once a day and calcium and vitamin D supplementation. In addition, osteopenic patients were randomized to receive either treatment with ibandronate 150 mg orally every month or placebo. After 2 years, osteopenic patients treated with ibandronate gained +2.98% (range -8.9, +19.9) and +0.60% (range -9.0, +6.9) at the lumbar spine and hip, respectively. Patients treated with placebo, however, lost -3.22% (range -16.0, +4.3) at the lumbar spine and -3.90% (range -12.3, +7.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (P < 0.01). At 12 months, urinary n-telopeptide, serum c-telopeptide, and serum bone-specific alkaline phosphatase levels declined in patients receiving ibandronate (30.9%, 26.3%, and 22.8%, respectively) and increased in those taking placebo (40.3%, 34.9%, and 37.0%, respectively). Monthly oral ibandronate improves bone density and normalizes bone turnover in patients treated with anastrozole.

  17. TRAF6 Mediates Suppression of Osteoclastogenesis and Prevention of Ovariectomy-Induced Bone Loss by a Novel Prenylflavonoid.

    Science.gov (United States)

    Tan, Ee Min; Li, Lei; Indran, Inthrani Raja; Chew, Nicholas; Yong, Eu-Leong

    2017-04-01

    Given the limitations of current therapeutic options for postmenopausal osteoporosis, there is a need for alternatives with minimal adverse effects. In this study, we evaluated the effects of icaritin (ICT), a natural prenylflavonoid, on osteoclastogenesis both in vitro and in an ovariectomized (OVX) rat model and investigated its underlying molecular mechanism(s) of action. ICT inhibited osteoclast formation in two osteoclast precursor models, RAW 264.7 mouse monocyte cell line and human PBMC. ICT also inhibited sealing zone and resorption pit formation in a dose-dependent manner. Mechanistically, ICT inhibited RANKL-induced NF-κB and MAPK/AP-1 pathways to suppress gene expression of nuclear factor of activated T cells (NFAT)c1, the master transcription regulator of osteoclast differentiation. ICT, by inhibiting the TRAF6/c-Src/PI3K pathway, suppressed NADPH oxidase-1 activation to attenuate intracellular ROS production and downregulate calcineurin phosphatase activity. As a result, NFATc1 nuclear translocation and activity was suppressed. Crucially, ICT promoted proteasomal degradation of TRAF6, the critical adaptor protein that transduces RANKL/RANK signaling, and the inhibitory effect of ICT on osteoclastogenesis was reversed by the proteasomal inhibitor MG 132. ICT administration inhibited OVX-induced bone loss and resorption by suppressing osteoclast formation and activity. Consistent with cellular studies, ICT downregulated TRAF6 and NFATc1 protein expression in CD11b + /Gr-1 -/low osteoclast precursors isolated from OVX rats. Put together, we present novel findings that ICT, by downregulating TRAF6, coordinates inhibition of NF-κB, MAPK/AP-1, and ROS signaling pathways to reduce expression and activity of NFATc1. These results demonstrate the potential of ICT for treatment of postmenopausal osteoporosis and point to TRAF6 as a promising target for novel anti-osteoporotic drugs. © 2017 American Society for Bone and Mineral Research. © 2017 American

  18. Bone Loss Prevention of Bisphosphonates in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yan Hu

    2017-01-01

    Full Text Available Objective. The purpose of this study was to evaluate the effect of bisphosphonates in improving bone mineral density (BMD and decreasing the occurrence rate of fractures and adverse events in patients with inflammatory bowel disease (IBD. Methods. Randomized controlled trials (RCTs which use bisphosphonates in IBD patients were identified in PubMed, MEDLINE database, EMBASE database, Web of Knowledge, and the Cochrane Databases between 1990 and June 2016. People received bisphosphonate or placebos with a follow-up of at least one year were also considered. STATA 12.0 software was used for the meta-analysis. Results. Eleven randomized clinical trials were included in the meta-analysis. The data indicated that the percentage change in the increased BMD in the bisphosphonates groups was superior to that of the control groups at the lumbar spine and total hip. At the femoral neck, there was no significant difference between the two groups. The incidence of new fractures during follow-up showed significant reduction. The adverse event analysis revealed no significant difference between the two groups. Conclusion. Our results demonstrate that bisphosphonates therapy has an effect on bone loss in patients with IBD but show no evident efficiency at increasing the incidence of adverse events.

  19. Preventing and Treating Brittle Bones and Osteoporosis | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... Javascript on. Feature: Osteoporosis Preventing and Treating Brittle Bones and Osteoporosis Past Issues / Winter 2011 Table of ... at high risk due to low bone mass. Bone and Bone Loss Bone is living, growing tissue. ...

  20. Oxygen ultra-fine bubbles water administration prevents bone loss of glucocorticoid-induced osteoporosis in mice by suppressing osteoclast differentiation.

    Science.gov (United States)

    Noguchi, T; Ebina, K; Hirao, M; Morimoto, T; Koizumi, K; Kitaguchi, K; Matsuoka, H; Iwahashi, T; Yoshikawa, H

    2017-03-01

    Oxygen ultra-fine bubbles (OUB) saline injection prevents bone loss of glucocorti\\coid-induced osteoporosis in mice, and OUB inhibit osteoclastogenesis via RANK-TRAF6-c-Fos-NFATc1 signaling and RANK-p38 MAPK signaling in vitro. Ultra-fine bubbles (osteoporosis (GIO) model mice. Prednisolone (PSL, 5 mg) was subcutaneously inserted in 6-month-old male C57BL/6J mice, and 200 μl of saline, OUB-diluted saline, or nitrogen ultra-fine bubbles (NUB)-diluted saline was intraperitoneally injected three times per week for 8 weeks the day after operations. Mice were divided into four groups; (1) control, sham-operation + saline; (2) GIO, PSL + saline; (3) GIO + OUB, PSL + OUB saline; (4) GIO + NUB, PSL + NUB saline. The effects of OUB on osteoblasts and osteoclasts were examined by serially diluted OUB medium in vitro. Bone mass was significantly decreased in GIO [bone volume/total volume (%): control vs. GIO 12.6 vs. 7.9; p suppressed in GIO + OUB (GIO vs. GIO + OUB 11.6 vs. 7.5; p osteoclastogenesis by inhibiting RANK-TRAF6-c-Fos-NFATc1 signaling, RANK-p38 MAPK signaling, and TRAP/Cathepsin K/DC-STAMP mRNA expression in a concentration-dependent manner. OUB did not affect osteoblastogenesis in vitro. OUB prevent bone loss in GIO mice by inhibiting osteoclastogenesis.

  1. A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5

    OpenAIRE

    Xin, Zhi; Jin, Cui; Chao, Liu; Zheng, Zhang; Liehu, Cao; Panpan, Pan; Weizong, Weng; Xiao, Zhai; Qingjie, Zhao; Honggang, Hu; Longjuan, Qin; Xiao, Chen; Jiacan, Su

    2018-01-01

    Post-menopausal osteoporosis (PMOP) is a metabolic bone disorder characterized by low bone mass and micro-architectural deterioration of bone tissue. The over-activated osteoclastogenesis, which plays an important role in osteoporosis, has become an important therapeutic target. M54 was a bioactive derivative of the Chinese traditional herb matrine. We found that M54 could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells and RAW264.7 cells through suppressing NF-κB, ...

  2. A standardized Humulus lupulus (L.) ethanol extract partially prevents ovariectomy-induced bone loss in the rat without induction of adverse effects in the uterus.

    Science.gov (United States)

    Keiler, Annekathrin M; Helle, Janina; Bader, Manuela I; Ehrhardt, Tino; Nestler, Kristin; Kretzschmar, Georg; Bernhardt, Ricardo; Vollmer, Günter; Nikolić, Dejan; Bolton, Judy L; Pauli, Guido F; Chen, Shao-Nong; Dietz, Birgit M; van Breemen, Richard B; Zierau, Oliver

    2017-10-15

    Hops (Humulus lupulus (L.)) dietary supplements are of interest as herbal remedies to alleviate menopausal symptoms, such as hot flushes, depression and anxiety. So far, the evidence regarding estrogenic and related properties of hops preparations has been considered insufficient for a market authorization for menopausal indications. The study aims to investigate a chemically standardized hops extract regarding its safety in the uterus, as wells as its efficacy to prevent bone loss in the ovariectomized rat model. Female Wistar rats were ovariectomized and divided into a control group receiving phytoestrogen-free diet, a group treated with E 2 benzoate (0.93 mg/kg body weight/d) and a group treated with the standardized hops extract (60 mg/kg body weight/d) for 8 weeks. Micro-computed tomography of the tibiae and vertebrae, as wells as histological changes in the uterus and tibia were analyzed. Neither uterotrophic nor proliferative effects were observed in the endometrium in response to the oral 8-week administration of the hops extract. However, site-dependent skeletal effects were observed. The hops extract significantly decreased the number of osteoclasts in the tibial metaphysis and prevented reduction of the trabecular thickness that resulted from estradiol depletion. In contrast, the hops extract did not prevent the ovariectomy-induced micro-architectural changes in the lumbar vertebra. Certain parameters (e.g. thickness and number of trabeculae) were even found to be below the values determined in the ovariectomized control group. Taken together, the results provide evidence for the safety of the standardized hops extract and point to a weak bone type-specific, protective effect on bone loss following estradiol depletion. Copyright © 2017. Published by Elsevier GmbH.

  3. Synergistic role of hydroxyapatite nanoparticles and pulsed electromagnetic field therapy to prevent bone loss in rats following exposure to simulated microgravity

    Directory of Open Access Journals (Sweden)

    D Prakash

    2009-07-01

    Full Text Available D Prakash, J BehariSchool of Environmental Sciences, Jawaharlal Nehru University, New Delhi, IndiaAbstract: The purpose of the present study was to use capacitive coupling of pulsed electromagnetic field (CC-PEMF and hydroxyapatite nanoparticles (HAp as a countermeasure to prevent osteoporosis induced by simulated microgravity. We used the hind-limb suspension (HLS rat model to simulate microgravity-induced bone losses for 45 days. In order to compare the resulting changes, mineralogical (bone mineral density [BMD], calcium [Ca], and phosphorus [P], biochemical (osteocalcin, alkaline phosphatase [ALP], and type I collagen, and histological (scanning electron microscopy parameters were adopted. As a countermeasure to the above, the effect of PEMF and HAp application were examined. Three-month-old female Wistar rats were randomly divided into control (n = 8, HLS (n = 8, HLS with PEMF (n = 8, HLS with HAp nanoparticles (n = 8, and HLS with HAp and PEMF (n = 8. We observed: 1 significant decrease (p < 0.01 in BMD, Ca, P, type I collagen, and ALP activity in femur and tibia in hind-limb bone and serum osteocalcin in HLS rats as compared with the ground control. 2 Nonsignificant increase in BMD (p < 0.1, Ca (p < 0.1, P (p < 0.5, type I collagen (p < 0.1, and ALP activity (p < 0.5 in femur and tibia in hind-limb bone and serum osteocalcin (p < 0.5 in HLS + PEMF rats compared with HLS rats. 3 Significant increase in BMD (p < 0.02, Ca (p < 0.05, P (p < 0.05, type I collagen (p < 0.02, and ALP activity (p > 0.02 in femur and tibia in hind-limb bone with a nonsignificant increase in serum osteocalcin (p > 0.1 in HLS + HAp rats compared to HLS rats. 4 Significant increase in BMD (p > 0.01. Ca (p > 0.01. P (p > 0.01. type I collagen (p > 0.01. and ALP activity (p > 0.01 in femur and tibia in hind-limb bone and serum osteocalcin (p > 0.02 were also observed. Results suggest that a combination of low level PEMF and Hap nanoparticles has potential to control

  4. Novel Radiomitigator for Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

    2016-01-01

    Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

  5. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    Science.gov (United States)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeff; Shapiro, Jay; Lang, Tom; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth; hide

    2011-01-01

    Experiment Hypothesis -- The combined effect of anti-resorptive drugs plus in-flight exercise regimen will have a measurable effect in preventing space flight induced bone mass and strength loss and reducing renal stone risk.

  6. Critical appraisal of denosumab in the treatment and prevention of postmenopausal osteoporosis and bone loss in patients undergoing hormone ablation

    Directory of Open Access Journals (Sweden)

    David L Kendler

    2010-09-01

    Full Text Available David L Kendler1, Kenneth Shawn Davison21Prohealth Clinical Research, University of British Columbia, Vancouver, British Columbia, Canada; 2Department of Medicine, Division of Immunology and Rheumatology, Laval University, Quebec, CanadaAbstract: Antiresorptive therapies are the mainstay for treating patients with excessively high rates of bone resorption. The receptor activator of nuclear factor-κB (RANK ligand (RANKL, secreted by osteoblasts, binds to the RANK receptor on the surface of preosteoclasts and osteoclasts to elicit osteoclast formation, survival, and activity. Osteoprotegerin, also secreted by the osteoblast, acts as a decoy RANK receptor reducing RANKL binding to RANK and reducing bone resorption. Denosumab, a fully human monoclonal antibody, has a high affinity and specificity for RANKL. Denosumab rapidly decreases bone resorption and increases bone mineral density (BMD at the lumbar spine, total hip, femoral neck, and one-third radius sites. In head-to-head trials, denosumab increased BMD and decreased bone resorption to a significantly greater degree than alendronate. In postmenopausal osteoporotic women, denosumab decreased the risk of vertebral fracture (68%, nonvertebral fracture (20%, and hip fracture (40% over 36 months, compared to placebo. In patients with iatrogenic hypogonadism, denosumab rapidly decreased markers of bone resorption and increased BMD. In men treated with GnRH agonist for prostate cancer, treatment with denosumab led to a 62% decreased risk of new vertebral fracture over 3 years, as compared to placebo. In all trials completed to date, comparable adverse events have been observed in both denosumab and placebo or treatment groups.Keywords: medication adherence, fracture, bone mineral density, bone turnover markers

  7. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Spielman, Danièle

    2004-01-01

    bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy...

  8. Soy protein isolates prevent loss of bone quantity associated with obesity in rats through regulation of insulin signaling in osteoblasts

    Science.gov (United States)

    In both rodents and humans, excessive consumption of a typical Western diet high in saturated fats and cholesterol is known to result in disruption of energy metabolism and development of obesity and insulin resistance. However, how these high-fat, energy-dense diets affect bone development, morphol...

  9. Noise and Hearing Loss Prevention

    Science.gov (United States)

    ... message, please visit this page: About CDC.gov . NOISE AND HEARING LOSS PREVENTION Language: English (US) Español ( ... when hazardous noise levels cannot be adequately reduced. Noise and Hearing Loss on the NIOSH Science Blog ...

  10. The osteoimmunology of alveolar bone loss.

    Science.gov (United States)

    Tompkins, Kevin A

    2016-01-01

    The mineralized structure of bone undergoes constant remodeling by the balanced actions of bone-producing osteoblasts and bone-resorbing osteoclasts (OCLs). Physiologic bone remodeling occurs in response to the body's need to respond to changes in electrolyte levels, or mechanical forces on bone. There are many pathological conditions, however, that cause an imbalance between bone production and resorption due to excessive OCL action that results in net bone loss. Situations involving chronic or acute inflammation are often associated with net bone loss, and research into understanding the mechanisms regulating this bone loss has led to the development of the field of osteoimmunology. It is now evident that the skeletal and immune systems are functionally linked and share common cells and signaling molecules. This review discusses the signaling system of immune cells and cytokines regulating aberrant OCL differentiation and activity. The role of these cells and cytokines in the bone loss occurring in periodontal disease (PD) (chronic inflammation) and orthodontic tooth movement (OTM) (acute inflammation) is then described. The review finishes with an exploration of the emerging role of Notch signaling in the development of the immune cells and OCLs that are involved in osteoimmunological bone loss and the research into Notch signaling in OTM and PD.

  11. Alveolar bone loss in obese subjects.

    Science.gov (United States)

    Alabdulkarim, Maher; Bissada, Nabil; Al-Zahrani, Mohammad; Ficara, Anthony; Siegel, Burton

    2005-04-01

    Obesity was found to be significantly associated with periodontal disease prevalence as measured by probing depth and clinical attachment loss. The aim of this study was to examine if obesity correlates with chronic periodontitis as diagnosed by radiographic alveolar bone loss. Four hundred subjects > or =18 years old were included; 200 with body mass index (BMI) > or =30 kg/m2 (obese) and 200 with BMI periodontitis. Obesity was found to be significantly associated with periodontitis in the uni-variate regression analysis (OR = 2.37, 95% CI, 1.55-3.63). After adjusting for age, gender, smoking, employment, diabetes, marital status, and number of teeth present, obese subjects were found to be 1.86 times more likely to have periodontitis (95% CI, 0.99-3.51) than non-obese ones. When the sample was stratified based on age, the multivariate association was statistically significant among individuals or = 40 years of age the association was statistically insignificant (OR = 1.06, 95% CI, 0.57-1.95). Stratifying the sample based on gender and smoking status revealed a stronger association among females than males (OR = 3.14 vs. 1.95) and among non-smokers than smokers (OR = 3.36 vs. 2.22). Obesity is associated with increased prevalence of periodontitis as measured by radiographic alveolar bone loss, especially among younger individuals. Prevention and management of obesity may be considered to promote better systemic and periodontal health.

  12. Role of Oxidative Damage in Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

  13. Horizontal alveolar bone loss: A periodontal orphan

    Directory of Open Access Journals (Sweden)

    Jayakumar A

    2010-01-01

    Full Text Available Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician′s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs (of patients diagnosed with chronic periodontitis and seeking periodontal care, which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36% OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2% teeth, and vertical defects were found only in 264 (7.8% of the teeth, which was statistically significant (P<.001. Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3% have addressed vertical bone loss, and 18 (3.7% have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment

  14. The Efficacy of Bisphosphonates in Preventing Aromatase Inhibitor Induced Bone Loss for Postmenopausal Women with Early Breast Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Pooleriveetil Padikkal Anagha

    2014-01-01

    Full Text Available Objectives. We aim to determine the efficacy of bisphosphonates in preventing aromatase inhibitor induced bone loss (AIBL in postmenopausal women with early breast cancer. The secondary objective was to determine the safety of bisphosphonates. Materials and Methods. We searched electronic databases in a time period of 1995 January to 2013 June. Random effects meta-analytical models were used; between study heterogeneity and publication bias was assessed. Results. A total of six eligible studies reported the BMD T score of LS at 12 months and from that 3 trials of Zoledronic acid compared the change in BMD in immediate ZOL versus delayed ZOL done with subgroups like patients with normal BMD at baseline (OR = 5.402, 95% CI = 1.329–21.959, P value = 0.018 and osteopenic BMD at baseline (OR = 4.008, 95% CI = 2.249–7.143, P value = 0.0002. Both had a significant decrease in BMD that favoured the delayed ZOL; 3 trials of risedronate and ibandronate also had a significant decrease in BMD in AIs alone group. Immediate ZOL versus delayed ZOL also showed increased risk of getting an ADR in immediate group. Conclusion. Third generation bisphosphonates has an effect on BMD of patients who are on treatment of AIs in breast cancer. Furthermore, the patients treated with immediate ZOL had a significantly high risk of musculoskeletal ADR’s than patients with delayed ZOL.

  15. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    Full Text Available The gut microbiota (GM modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L strain, L. paracasei DSM13434 (L. para or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  16. Efficacy of gallium in tooth loss prevention

    Directory of Open Access Journals (Sweden)

    Aleksić Milena D.

    2016-01-01

    Full Text Available Introduction: Over the past three decades, gallium compounds have gained importance in medicine. Radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti inflammatory and immunosuppressive activity in animal models of human diseases. More recent studies have shown that gallium compounds may also function as antimicrobial agents. In the review, the potential application of gallium in the future treatment of periodontitis and prevention of tooth loss will be discussed. Gingival inflammation, bacterial infection, alveolar bone destruction and subsequent tooth loss are characteristic features of periodontal disease. Surgical techniques, mechanical debridement of the denuded root surface, and local or systemic application of antimicrobial agents are currently used treatments for periodontitis. However, the development of antibiotic resistance in bacteria has prompted a great need for new and alternative treatment methods for infection. Conclusion: The potential anti-periodontitis benefits of gallium are related to eradicating infection due to bacterial biofilms, increasing bone deposition and downregulating unwanted immune responses. Adjunctive use of gallium laser therapy with mechanical instrumentation in combination with gallium-containing gingival gels, toothpastes and mouth rinses may represent the final solutions for tooth loss prevention.

  17. Bone loss following knee arthroplasty: potential treatment options.

    Science.gov (United States)

    Vasso, Michele; Beaufils, Philippe; Cerciello, Simone; Schiavone Panni, Alfredo

    2014-04-01

    The management of bone loss is a crucial aspect of the revision knee arthroplasty. Bone loss can hinder the correct positioning and alignment of the prosthetic components, and can prevent the achievement of a stable bone-implant interface. There is still controversy regarding the optimal management of knee periprosthetic bone loss, especially in large defects for which structural grafts, metal or tantalum augments, tantalum cones, porous metaphyseal sleeves, and special prostheses have been advocated. The aim of this review was to analyze all possible causes of bone loss and the most advanced strategies for managing bony deficiency within the knee joint reconstruction. Most significant and recent papers about the management of bone defects during revision knee arthroplasty were carefully analyzed and reviewed to report the most common causes of bone loss and the most effective strategies to manage them. Modular metal and tantalum augmentation showed to provide more stable and durable knee revisions compared to allografts, limited by complications such as graft failure, fracture and resorption. Moreover, modular augmentation may considerably shorten operative times with a potential decrease of complications, above all infection which has been frequently associated to the use of allografts. Modular augmentation may significantly reduce the need for allografting, whose complications appear to limit the long-term success of knee revisions.

  18. Bed Rest and Immobilization: Risk Factors for Bone Loss

    Science.gov (United States)

    ... Risk Factors for Bone Loss Bed Rest and Immobilization: Risk Factors for Bone Loss Like muscle, bone ... complications of pregnancy; and those who are experiencing immobilization of some part of the body because of ...

  19. Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model

    Science.gov (United States)

    The purpose of this study was to explore bioavailability, efficacy, and molecular mechanisms of green tea polyphenols (GTP) related to preventing bone loss in rats with chronic inflammation. A 2 (placebo vs. lipopolysaccharide, LPS) × 2 (no GTP vs. 0.5% GTP in drinking water) factorial design using ...

  20. Interleukin-10 Inhibits Bone Resorption: A Potential Therapeutic Strategy in Periodontitis and Other Bone Loss Diseases

    OpenAIRE

    Zhang, Qian; Chen, Bin; Yan, Fuhua; Guo, Jianbin; Zhu, Xiaofeng; Ma, Shouzhi; Yang, Wenrong

    2014-01-01

    Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases...

  1. Sialoglycoproteins prepared from the eggs of Carassius auratus prevent bone loss by inhibiting the NF-κB pathway in ovariectomized rats.

    Science.gov (United States)

    Xia, Guanghua; Wang, Jingfeng; Sun, Shuhong; Zhao, Yanlei; Wang, Yiming; Yu, Zhe; Wang, Shanshan; Xue, Changhu

    2016-02-01

    In this study, we investigated the improvement of osteoporosis by sialoglycoproteins isolated from the eggs of Carassius auratus (Ca-SGP) in ovariectomized rats. Ca-SGP was supplemented to ovariectomized Sprague-Dawley rats for 90 days. The results showed that Ca-SGP treatment remarkably prevented the reduction of bone mass, improved cancellous bone structure and biochemical properties. Ca-SGP also significantly decreased the serum contents of TRAP, Cath-K, MMP-9, DPD, CTX-1, Ca, and P. Mechanism investigation revealed that Ca-SGP significantly increased the OPG/RANKL ratio in mRNA expression, protein expression and serum content. Further research suggested that NF-κB signaling pathways were inhibited by suppressing the mRNA and protein expressions of NFATc1 and TRAF6, diminishing the mRNA expression and phosphorylation of NF-κB p65, three key transcription factors in NF-κB pathways. These results suggest that Ca-SGP can improve osteoporosis by inhibiting bone resorption via suppressing the activation of osteoclastogenesis related NF-κB pathways.

  2. Vitamin C reverses hypogonadal bone loss

    Science.gov (United States)

    Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, ...

  3. Bone Loss During Spaceflight: Available Models and Counter-Measures

    Science.gov (United States)

    Morris, Jonathan; Bach, David; Geller, David

    2015-01-01

    There is ongoing concern for human health during spaceflights. Of particular interest is the uncoupling of bone remodeling and its resultant effect on calcium metabolism and bone loss. The calculated average loss of bone mineral density (BMD) is approximately 1-1.5% per month of spaceflight. The effect of decreased BMD on associated fractures in astronauts is not known. Currently on the International Space Station (ISS), bone loss is managed through dietary supplements and modifications and resistance exercise regimen. As the duration of space flights increases, a review of the current methods available for the prevention of bone loss is warranted. The goal of this project is to review and summarize recent studies that have focused on maintaining BMD during exposure to microgravity. Interventions were divided into physical (Table 1), nutritional (Table 2), or pharmacologic (Table 3) categories. Physical modalities included resistance exercise, low level vibration, and low intensity pulsed ultrasound. Nutritional interventions included altering protein, salt, and fat intake; and vitamin D supplementation. Pharmacologic interventions included the use of bisphosphonates and beta blockers. Studies reported outcomes based on bone density determined by DXA bone scan, micro-architecture of histology and microCT, and serum and urine markers of bone turnover. The ground analog models utilized to approximate osseous physiology in microgravity included human patients previously paralyzed or subjects confined to bedrest. Ground analog animal models include paralysis, immobilization and ovariectomies. As a result of the extensive research performed there is a multi-modality approach available for the management of BMD during spaceflight that includes resistance training, nutrition and dietary supplements. However, there is a paucity of literature describing a formalized tiered protocol to guide investigators through the progression from animal models to human patient ground

  4. Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) show microstructural bone loss during hibernation but preserve bone macrostructural geometry and strength.

    Science.gov (United States)

    McGee-Lawrence, Meghan E; Stoll, Danielle M; Mantila, Emily R; Fahrner, Bryna K; Carey, Hannah V; Donahue, Seth W

    2011-04-15

    Lack of activity causes bone loss In most animals. Hibernating bears have physiological processes to prevent cortical and trabecular bone loss associated with reduced physical activity, but different mechanisms of torpor among hibernating species may lead to differences in skeletal responses to hibernation. There are conflicting reports regarding whether small mammals experience bone loss during hibernation. To investigate this phenomenon, we measured cortical and trabecular bone properties in physically active and hibernating juvenile and adult 13-lined ground squirrels (Ictidomys tridecemlineatus, previous genus name Spermophilus). Cortical bone geometry, strength and mineral content were similar in hibernating compared with active squirrels, suggesting that hibernation did not cause macrostructural cortical bone loss. Osteocyte lacunar size increased (linear regression, P=0.001) over the course of hibernation in juvenile squirrels, which may indicate an osteocytic role in mineral homeostasis during hibernation. Osteocyte lacunar density and porosity were greater (+44 and +59%, respectively; Phibernating compared with active squirrels, which may reflect a decrease in osteoblastic activity (per cell) during hibernation. Trabecular bone volume fraction in the proximal tibia was decreased (-20%; P=0.028) in hibernating compared with physically active adult squirrels, but was not different between hibernating and active juvenile squirrels. Taken together, these data suggest that 13-lined ground squirrels may be unable to prevent microstructural losses of cortical and trabecular bone during hibernation, but importantly may possess a biological mechanism to preserve cortical bone macrostructure and strength during hibernation, thus preventing an increased risk of bone fracture during remobilization in the spring.

  5. Bone Loss Among Women Living With HIV.

    Science.gov (United States)

    Weitzmann, M Neale; Ofotokun, Ighovwerha; Titanji, Kehmia; Sharma, Anjali; Yin, Michael T

    2016-12-01

    Clinical data accumulated over the past two decades attests to a significant decline in bone mineral density (BMD) in patients infected by HIV, which does not remit but may actually intensify with anti-retroviral therapy (ART). Long generally perceived as an aberration without clinical consequences in relatively young HIV-infected cohorts, recent studies have documented marked increases in fracture incidence in HIV-infected men and women over a wide age continuum. Fractures are associated with chronic pain, crippling morbidity, and increased mortality, undermining the gains in quality of life achieved though ART. As bone loss and resulting increases in fracture incidence are a natural consequence of aging, there is now concern regarding the long-term consequences of HIV/ART-associated premature bone loss, given the transition of the HIV/AIDS population into an older age demographic. The development of guidelines for diagnosis and treatment of bone disease within the context of HIV and ART has been an important recent step in raising awareness of the problem and the implications of bone fracture for patient health. Significant progress has also been made in recent years in dissecting the complex and multifactorial mechanisms driving bone loss in HIV/ART and the role of underlying immunological disruption in skeletal dysmorphogenesis. This review examines recent progress in the field and studies by Women's Interagency HIV Study (WIHS)-associated investigators, inside and outside of the WIHS cohort, aimed at identifying skeletal abnormalities, quantifying facture incidence, management, and understanding underlying mechanisms in people living with HIV in the context of chronic ART.

  6. Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

    International Nuclear Information System (INIS)

    Choo, Richard; Lukka, Himu; Cheung, Patrick; Corbett, Tom; Briones-Urbina, Rosario; Vieth, Reinhold; Ehrlich, Lisa; Kiss, Alex; Danjoux, Cyril

    2013-01-01

    Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT

  7. Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Choo, Richard [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Lukka, Himu [Department of Radiation Oncology, Juravinski Cancer Center, McMaster University, Hamilton (Canada); Cheung, Patrick [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto (Canada); Corbett, Tom [Department of Radiation Oncology, Juravinski Cancer Center, McMaster University, Hamilton (Canada); Briones-Urbina, Rosario [Department of Medicine, Women' s College Hospital, University of Toronto, Toronto (Canada); Vieth, Reinhold [Departments of Nutritional Sciences and Laboratory Medicine and Pathology, Mount Sinai Hospital, University of Toronto, Toronto (Canada); Ehrlich, Lisa [Department of Radiology, Sunnybrook Health Sciences Center, University of Toronto (Canada); Kiss, Alex [Department of Health Policy, Management, and Evaluation, Sunnybrook Health Sciences Center, University of Toronto, Toronto (Canada); Danjoux, Cyril, E-mail: Cyril.danjoux@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto (Canada)

    2013-04-01

    Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.

  8. Interleukin-10 Inhibits Bone Resorption: A Potential Therapeutic Strategy in Periodontitis and Other Bone Loss Diseases

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    2014-01-01

    Full Text Available Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10 is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

  9. Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases.

    Science.gov (United States)

    Zhang, Qian; Chen, Bin; Yan, Fuhua; Guo, Jianbin; Zhu, Xiaofeng; Ma, Shouzhi; Yang, Wenrong

    2014-01-01

    Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

  10. Prevention and Treatment of Bone Metastases in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ripamonti Carla

    2013-09-01

    Full Text Available In breast cancer patients, bone is the most common site of metastases. Medical therapies are the basic therapy to prevent distant metastases and recurrence and to cure them. Radiotherapy has a primary role in pain relief, recalcification and stabilization of the bone, as well as the reduction of the risk of complications (e.g., bone fractures, spinal cord compression. Bisphosphonates, as potent inhibitors of osteoclastic-mediated bone resorption are a well-established, standard-of-care treatment option to reduce the frequency, severity and time of onset of the skeletal related events in breast cancer patients with bone metastases. Moreover bisphosphonates prevent cancer treatment-induced bone loss. Recent data shows the anti-tumor activity of bisphosphonates, in particular, in postmenopausal women and in older premenopausal women with hormone-sensitive disease treated with ovarian suppression. Pain is the most frequent symptom reported in patients with bone metastases, and its prevention and treatment must be considered at any stage of the disease. The prevention and treatment of bone metastases in breast cancer must consider an integrated multidisciplinary approach.

  11. Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

    Directory of Open Access Journals (Sweden)

    Tae-Ho Kim

    2016-01-01

    Full Text Available Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr cocoons spun by Rhus javanica (Bell. Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr or 100% ethanolic extract (eeGr on ovariectomy- (OVX- induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks augmented the inhibition of femoral bone mineral density (BMD, bone mineral content (BMC, and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

  12. Regenerate augmentation with bone marrow concentrate after traumatic bone loss

    Directory of Open Access Journals (Sweden)

    Jan Gessmann

    2012-03-01

    Full Text Available Distraction osteogenesis after post-traumatic segmental bone loss of the tibia is a complex and time-consuming procedure that is often complicated due to prolonged consolidation or complete insufficiency of the regenerate. The aim of this feasibility study was to investigate the potential of bone marrow aspiration concentrate (BMAC for percutaneous regenerate augmentation to accelerate bony consolidation of the regenerate. Eight patients (age 22-64 with an average posttraumatic bone defect of 82.4 mm and concomitant risk factors (nicotine abuse, soft-tissue defects, obesity and/or circulatory disorders were treated with a modified Ilizarov external frame using an intramedullary cable transportation system. At the end of the distraction phase, each patient was treated with a percutaneously injection of autologous BMAC into the centre of the regenerate. The concentration factor was analysed using flow cytometry. The mean follow up after frame removal was 10 (4-15 months. With a mean healing index (HI of 36.9 d/cm, bony consolidation of the regenerate was achieved in all eight cases. The mean concentration factor of the bone marrow aspirate was 4.6 (SD 1.23. No further operations concerning the regenerate were needed and no adverse effects were observed with the BMAC procedure. This procedure can be used for augmentation of the regenerate in cases of segmental bone transport. Further studies with a larger number of patients and control groups are needed to evaluate a possible higher success rate and accelerating effects on regenerate healing.

  13. Evaluating Bone Loss in ISS Astronauts.

    Science.gov (United States)

    Sibonga, Jean D; Spector, Elisabeth R; Johnston, Smith L; Tarver, William J

    2015-12-01

    The measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is the Medical Assessment Test used at the NASA Johnson Space Center to evaluate whether prolonged exposure to spaceflight increases the risk for premature osteoporosis in International Space Station (ISS) astronauts. The DXA scans of crewmembers' BMD during the first decade of the ISS existence showed precipitous declines in BMD for the hip and spine after the typical 6-mo missions. However, a concern exists that skeletal integrity cannot be sufficiently assessed solely by DXA measurement of BMD. Consequently, use of relatively new research technologies is being proposed to NASA for risk surveillance and to enhance long-term management of skeletal health in long-duration astronauts. Sibonga JD, Spector ER, Johnston SL, Tarver WJ. Evaluating bone loss in ISS astronauts.

  14. (-)-Epicatechin 3-O-β-D-allopyranoside prevent ovariectomy-induced bone loss in mice by suppressing RANKL-induced NF-κB and NFATc-1 signaling pathways.

    Science.gov (United States)

    Hsiao, Hung-Bo; Wu, Jin-Bin; Lin, Wen-Chuan

    2017-05-03

    Davallia formosana Hayata is a herb that has been used in Chinese medicine to treat bone diseases, including arthritis, bone fractures and osteoporosis. The rhizome of D. formosana H. has been found to be rich in (-)-Epicatechin 3-O-β-D-allopyranoside (ECAP), which is considered to be the active component of the plant in terms of its antiosteoporotic effect. This study investigated the molecular mechanism of the antiosteoporotic property of ECAP isolated from the roots of D. formosana H. using both in vitro and in vivo models. We studied the effects of ECAP on the signaling pathways of the receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis and ovariectomy-induced osteoporosis. In the in vitro study, the inhibitory action of ECAP on RANKL-induced osteoclastogenesis and the expression of osteoclast-related marker genes were investigated, and in the in vivo study, the effects of ECAP on bone were evaluated using ovariectomized (OVX) mice orally-administered ECAP for 4 weeks. We demonstrated that ECAP dose-dependently inhibited RANKL- and nuclear factor of activated T-cells, and cytoplasmic 1 (NFATc-1)-induced osteoclastogenesis by RAW 264.7 cells, and reduced the extent of bone resorption. Furthermore, μCT images and TRAP staining showed that oral administration of ECAP to OVX mice prevented bone loss. ECAP administration also exerted recovery effects on serum C-terminal telopeptide of type I collagen and osteocalcin levels in OVX mice. In addition, we also found that MMP-9 expression was decreased in vivo and in vitro. Overall, our findings suggested that ECAP suppresses RANKL-induced osteoclastogenesis through NF-κB and NFATc-1 signaling pathways, and has the potential for use in osteoporosis treatment.

  15. Information Security - Data Loss Prevention Procedure

    Science.gov (United States)

    The purpose of this procedure is to extend and provide specificity to the Environmental Protection Agency (EPA) Information Security Policy regarding data loss prevention and digital rights management.

  16. Regional cortical and trabecular bone loss after spinal cord injury

    OpenAIRE

    Dudley-Javoroski, Shauna; Shields, Richard K.

    2012-01-01

    Spinal cord injury (SCI) triggers rapid loss of trabecular bone mineral density (BMD) in bone epiphyses and a loss of cortical cross-sectional area (CSA) in bone diaphyses, increasing fracture risk for people with SCI. The purpose of this study was to measure trabecular BMD and cortical CSA loss at several previously unexamined lower-limb sites (4% fibula, 12% femur, 86% tibia, cortical) in individuals with SCI. Using peripheral quantitative computed tomography, we scanned 13 participants wit...

  17. Zanthoxylum piperitum reversed alveolar bone loss of periodontitis via regulation of bone remodeling-related factors.

    Science.gov (United States)

    Kim, Mi Hye; Lee, Hye Ji; Park, Jung-Chul; Hong, Jongki; Yang, Woong Mo

    2017-01-04

    Zanthoxylum piperitum (ZP) has been used to prevent toothache in East Asia. In this study, we investigated the effects of ZP on periodontitis along with alveolar bone loss. Twenty-eight male Sprague-Dawley rats were assigned into 4 groups; non-ligated (NOR), ligated and treated vehicle (CTR), ligated and treated 1mg/mL ZP (ZP1), and ligated and treated 100mg/mL ZP (ZP100). Sterilized 3-0 nylon ligature was placed into the subgingival sulcus around the both sides of mandibular first molar. After topical application of 1 and 100mg/mL ZP for 2 weeks, mandibles was removed for histology. In addition, SaOS-2 osteoblast cells were treated 1, 10 and 100μg/mL ZP for 24h to analyze the expressions of alveolar bone-related markers. Several alveolar bone resorption pits, which indicate cementum demineralization were decreased by ZP treatment. Topical ZP treatment inhibited periodontitis-induced alveolar bone loss. In addition, there were significant reduction of osteoclastic activities following topical ZP treatment in periodontium. The expression of RANKL was decreased in SaOS-2 osteoblast cells by treating ZP, while that of OPG was increased. ZP treatment increased the expressions of Runx2 and Osterix in SaOS-2 cells. In summary, ZP treatment inhibited alveolar bone loss as well as maintained the integrity of periodontal structures via regulation of bone remodeling. ZP may be a therapeutic target for treating periodontitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Prevention of bone loss in ovariectomized rats by combined treatment with risedronate and 1α,25-dihydroxyvitamin D3

    DEFF Research Database (Denmark)

    Erben, R.G.; Mosekilde, Li.; Thomsen, J.S.

    2002-01-01

    with rats receiving risedronate alone. Furthermore, calcitriol enhanced the suppressive effects of risedronate on osteoclast number and partially counteracted the suppressive effects of risedronate on bone formation and histomorphometric indices of osteoblast team performance. Risedronate did not reduce...... the anabolic effect of calcitriol, and at the high dose it normalized hypercalcemia in calcitriol-treated OVX rats. Therefore, this study in OVX rats suggests that combined therapy with bisphosphonates and vitamin D analogs may offer advantages over the treatment with bisphosphonates or vitamin D analogs alone....

  19. Finite element analysis of bone loss around failing implants

    NARCIS (Netherlands)

    Wolff, J.E.H.; Narra, N.; Antalainen, A.K.; Valasek, J.; Kaiser, J.; Sandor, G.K.; Marcian, P.

    2014-01-01

    Dental implants induce diverse forces on their surrounding bone. However, when excessive unphysiological forces are applied, resorption of the neighbouring bone may occur. The aim of this study was to assess possible causes of bone loss around failing dental implants using finite element analysis. A

  20. Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss

    Directory of Open Access Journals (Sweden)

    Jong Min Baek

    2017-03-01

    Full Text Available In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR. Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca2+ influx intensity (staining with Fluo-3/AM. Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.

  1. Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss.

    Science.gov (United States)

    Baek, Jong Min; Kim, Ju-Young; Lee, Chang Hoon; Yoon, Kwon-Ha; Lee, Myeung Su

    2017-03-07

    In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP) staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR). Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca 2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca 2+ influx intensity (staining with Fluo-3/AM). Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.

  2. Preventing Vision Loss in Diabetes - Summary

    Centers for Disease Control (CDC) Podcasts

    2008-04-24

    This podcast is for a professional audience and briefly discusses how to prevent vision loss in people with diabetes.  Created: 4/24/2008 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Diabetes Translation (DDT), National Diabetes Education Program (NDEP).   Date Released: 6/4/2008.

  3. Glucocorticoid: A potential role in microgravity-induced bone loss

    Science.gov (United States)

    Yang, Jiancheng; Yang, Zhouqi; Li, Wenbin; Xue, Yanru; Xu, Huiyun; Li, Jingbao; Shang, Peng

    2017-11-01

    Exposure of animals and humans to conditions of microgravity, including actual spaceflight and simulated microgravity, results in numerous negative alterations to bone structure and mechanical properties. Although there are abundant researches on bone loss in microgravity, the explicit mechanism is not completely understood. At present, it is widely accepted that the absence of mechanical stimulus plays a predominant role in bone homeostasis disorders in conditions of weightlessness. However, aside from mechanical unloading, nonmechanical factors such as various hormones, cytokines, dietary nutrition, etc. are important as well in microgravity induced bone loss. The stress-induced increase in endogenous glucocorticoid (GC) levels is inevitable in microgravity environments. Moreover, it is well known that GCs have a detrimental effect to bone health at excess concentrations. Therefore, GC plays a potential role in microgravity-induced bone loss. This review summarizeds several studies and their prospective solutions to this hypothesis.

  4. Biologically rational ways of bone mass loss prophylaxis and treatment

    Directory of Open Access Journals (Sweden)

    A. S. Avrunin

    2015-01-01

    Full Text Available Aim. Based on own and literature date to define biologically rational elements of complex approach to bone mass loss prophylaxis and treatment. Nowadays there are two points of view regarding bone mass loss prophylaxis and treatment. The first favor pharmaceuticals as a basic and physical exercises as additional. According to the second, therapeutic and prophylactic significance of physical exercises in maintenance and development of structural and functional capacities of musculoskeletal system is fundamental. The latter approach correspond to evolutionary formed biological model in that muscles act upon levers - bones that connected by means of joints and provide the movement of the body against gravity. The present work from pathogenethically point of view establish the systemic approach to the bone mass loss prophylaxis and treatment. It is based on physical exercises while additional pharmacotherapy that should aim for optimization of regulatory function of bone cells, first of all osteocytes providing for adaptational reorganisation of bone structures.

  5. Digital radiographic evaluation of alveolar bone loss, density and lamina dura integrity on post splinting mandibular anterior with chronic periodontitis

    Science.gov (United States)

    Rafini, F.; Priaminiarti, M.; Sukardi, I.; Lessang, R.

    2017-08-01

    The healing of periodontal splinting can be detected both with clinical and radiographic examination. In this study, the alveolar bone was evaluated by radiographic digital periapical analysis. Periodontal tooth splinting is periodontal support therapy used to prevent periodontal injury during repair and regeneration of periodontal therapy. Radiographic digital periapical analysis of alveolar bone in the mandibular anterior region with chronic periodontitis and 2/3 cervical bone loss after three months of periodontal splinting. Eighty four proximal site (43 mesial and 41 distal) from 16 patients with chronic periodontitis and treated with spinting were examined by taking periapical digital radiographic at day 1 and 91. The bone loss, bone density and utility of lamina dura were evaluated. The statistical analysis after three months evaluation using T-test for bone loss, Wilcoxon sign rank test for bone density and utility lamina dura showed no significantly differences (palveolar bone loss after three months splinting.

  6. Recursos fisioterapêuticos na prevenção da perda da densidade mineral óssea com lesão medular Physiotherapy resources on bone mineral density loss prevention in patients with spinal cord injuries

    Directory of Open Access Journals (Sweden)

    Daniele Rodrigues

    2004-09-01

    Full Text Available Este trabalho é uma revisão bibliográfica sobre os tratamentos fisioterápicos destinados a prevenção, estabilização ou lentificação da perda da densidade mineral óssea em pacientes portadores de lesão medular. Foram encontrados poucos trabalhos que se destinaram aos tratamentos fisioterápicos para desmineralização óssea. Em relação aos tipos de tratamentos encontrados foram: estimulação elétrica funcional, estimulação elétrica funcional com bicicleta ergométrica, ortostatismo e deambulação. Estes tratamentos são bastante questionáveis não tendo um consenso na metodologia, apresentando muitas controvérsias em relação à eficácia dos tratamentos, que serão discutidos no decorrer deste trabalho.This work is bibliographic review about the physiotherapy treatments for the attenuation, prevention and stabilization or slowing down of the bone mineral density loss in spinal cord injured patients. There are few studies focusing the efficiency the physiotherapy treatment for bone demineralization. The kinds of treatments found were: functional electrical stimulation, functional electrical stimulation with an bycicle ergometry, orthostatic and deambulation. These treatments are much questionable, and with no consensus on the methodology, with the lot of controversies in relation to the efficacy of the treatments, which are going to be discussed in the development of this study.

  7. Uncovering effective strategies for hearing loss prevention

    Science.gov (United States)

    Morata, Thais C.; Meinke, Deanna

    2016-01-01

    Occupational health agencies, researchers and policy makers have recognized the need for evidence on the effectiveness of interventions designed to reduce or prevent workplace injuries and illnesses. While many workplaces comply with legal or obligatory requirements and implement recommended interventions, few publications exist documenting the effectiveness of these actions. Additionally, some workplaces have discovered through their own processes, novel ways to reduce the risk of injury. Peer-reviewed information on the effectiveness of the many strategies and approaches currently in use could help correct weaknesses, or further encourage their adoption and expansion. The evaluation of intervention effectiveness would certainly contribute to improved worker health and safety. This need is particularly relevant regarding noise exposure in the workplace and hearing loss prevention interventions. In a 2006 review of the U.S. National Institute for Occupational Safety and Health (NIOSH) Hearing Loss Research Program, the independent National Academies of Sciences recommended that NIOSH place greater emphasis on identifying the effectiveness of hearing loss prevention measures on the basis of outcomes that are as closely related as possible to reducing noise exposure and work related hearing loss (http://www.nap.edu/openbook.php?record_id=11721). NIOSH used two different approaches to address that recommendation: the first one was to conduct research, including broad systematic reviews on the effectiveness of interventions to prevent occupational noise-induced hearing loss. The second was to create an award program, the Safe-In-Sound Excellence in Hearing Loss Prevention Award™, to identify and honor excellent real-world examples of noise control and other hearing loss prevention practices and innovations. PMID:27397968

  8. Bone graft complications: what can we do to prevent them?

    Science.gov (United States)

    Tandon, Rahul; Herford, Alan S.

    2014-03-01

    Introduction: Bone grafts are commonly used in oral and maxillofacial surgery, helping to restore missing bone structure and provide osseous support. In spite of their reported success, complications can and do arise. Examples include loosening and resorption of the graft, infection, and complete loss of the graft. These complications can potentially lead to larger defects, necessitating additional procedures to correct the problem. This not only causes great discomfort to the patient, but also drains considerable time and resources away from the clinician. Thus, improvements on identifying ways to identify and prevent these complications are constantly being sought. We have performed a literature review and identified several areas in the field of optics that could potentially help solve our problem. Optical Techniques: Raman spectroscopy has been shown to provide a transcutaneous measurement of bone mineral and matrix Raman bands. This could potentially provide surgeons with the ability to more accurately assess bone graft osseointegration. In-vivo near-infrared optical imaging could potentially provide accurate diagnosis of pathologic lesions such as osteosarcoma. Contrast-enhanced ultrasound could be used to detect vascular disturbances and other information related to the transplantation of osseous components. Conclusion: Bone graft complications can be one of the most devastating consequences of osseous surgery. As surgeons, we are constantly searching for ways to identify them earlier and prevent them. We hope that by presenting areas that could be used, we can gain a better insight to ways in which both fields can benefit.

  9. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    Science.gov (United States)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  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. Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group

    DEFF Research Database (Denmark)

    Ravn, Pernille; Cizza, G; Bjarnason, N H

    1999-01-01

    Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n...... (r = -0.12 to -0.15, p mass parameters and response to alendronate treatment, which...... indicated that risk of low bone mass and increased bone loss caused by thinness could be compensated by alendronate treatment. In conclusion, thinness is an important risk factor for low bone mass and increased bone loss in postmenopausal women. Because the response to alendronate treatment is independent...

  12. Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

    Science.gov (United States)

    LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey A.; Shapiro, Jay; Lang, Thomas F.; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth; hide

    2009-01-01

    Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates) will determine whether antiresorptive agents, in conjunction with the routine inflight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS missions.

  13. Biglycan deficiency interferes with ovariectomy-induced bone loss

    DEFF Research Database (Denmark)

    Nielsen, Karina L; Allen, Matthew R; Bloomfield, Susan A

    2003-01-01

    Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response...

  14. Propranolol Attenuates Risperidone-Induced Trabecular Bone Loss in Female Mice.

    Science.gov (United States)

    Motyl, Katherine J; DeMambro, Victoria E; Barlow, Deborah; Olshan, David; Nagano, Kenichi; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

    2015-07-01

    Atypical antipsychotic (AA) drugs cause significant metabolic side effects, and clinical data are emerging that demonstrate increased fracture risk and bone loss after treatment with the AA, risperidone (RIS). The pharmacology underlying the adverse effects on bone is unknown. However, RIS action in the central nervous system could be responsible because the sympathetic nervous system (SNS) is known to uncouple bone remodeling. RIS treatment in mice significantly lowered trabecular bone volume fraction (bone volume/total volume), owing to increased osteoclast-mediated erosion and reduced osteoblast-mediated bone formation. Daytime energy expenditure was also increased and was temporally associated with the plasma concentration of RIS. Even a single dose of RIS transiently elevated expression of brown adipose tissue markers of SNS activity and thermogenesis, Pgc1a and Ucp1. Rankl, an osteoclast recruitment factor regulated by the SNS, was also increased 1 hour after a single dose of RIS. Thus, we inferred that bone loss from RIS was regulated, at least in part, by the SNS. To test this, we administered RIS or vehicle to mice that were also receiving the nonselective β-blocker propranolol. Strikingly, RIS did not cause any changes in trabecular bone volume/total volume, erosion, or formation while propranolol was present. Furthermore, β2-adrenergic receptor null (Adrb2(-/-)) mice were also protected from RIS-induced bone loss. This is the first report to demonstrate SNS-mediated bone loss from any AA. Because AA medications are widely prescribed, especially to young adults, clinical studies are needed to assess whether β-blockers will prevent bone loss in this vulnerable population.

  15. Local vibration enhanced the efficacy of passive exercise on mitigating bone loss in hindlimb unloading rats

    Science.gov (United States)

    Huang, Yunfei; Luan, Huiqin; Sun, Lianwen; Bi, Jingfang; Wang, Ying; Fan, Yubo

    2017-08-01

    Spaceflight induced bone loss is seriously affecting astronauts. Mechanical stimulation from exercise has been shown to restrain bone resorption as well as improve bone formation. Current exercise countermeasures in space cannot prevent it completely. Active exercise may convert to passive exercise in some ways because of the loss of gravity stimulus and inertia of exercise equipment. The aim of this study was to compare the efficacy of passive exercise or/and local vibration on counteracting the deterioration of the musculoskeletal system, including bone, muscle and tendons in tail-suspended rats. We hypothesized that local vibration could enhance the efficacy of passive exercise on countering bone loss. 40 Sprague Dawley rats were randomly distributed into five groups (n = 8, each): tail-suspension (TS), TS+35 Hz vibration (TSV), TS + passive exercise (TSP), TS + passive exercise coupled with 35 Hz vibration (TSPV) and control (CON). Passive exercise or/and local vibration was performed for 21 days. On day 0 and 21, bone mineral density (BMD) was observed by dual energy X-ray absorptiometry (DXA), and trabecular microstructure was evaluated by microcomputer tomography (μCT) analysis in vivo. Mechanical properties of tibia and tendon were determined by a mechanical testing system. Soleus and bone ash weight was tested by an electronic balance. Results showed that the passive exercise could not prevent the decrease of trabecular BMD, microstructure and bone ash weight induced by TS, whereas vibration and passive exercise coupled with local vibration (PV) could. Biomechanical properties of the tibia and tendon in TSPV group significantly increased compared with TS group. In summary, PV in this study was the best method in preventing weightlessness-induced bone loss. Consistent with our hypothesis, local vibration partly enhanced the effect of passive exercise. Furthermore, this study will be useful in improving countermeasure for astronauts, but also for the

  16. Building better bone: The weaving of biologic and engineering strategies for managing bone loss.

    Science.gov (United States)

    Schwartz, Andrew M; Schenker, Mara L; Ahn, Jaimo; Willett, Nick J

    2017-09-01

    Segmental bone loss remains a challenging clinical problem for orthopaedic trauma surgeons. In addition to the missing bone itself, the local tissues (soft tissue, vascular) are often highly traumatized as well, resulting in a less than ideal environment for bone regeneration. As a result, attempts at limb salvage become a highly expensive endeavor, often requiring multiple operations and necessitating the use of every available strategy (autograft, allograft, bone graft substitution, Masquelet, bone transport, etc.) to achieve bony union. A cost-sensitive, functionally appropriate, and volumetrically adequate engineered substitute would be practice-changing for orthopaedic trauma surgeons and these patients with difficult clinical problems. In tissue engineering and bone regeneration fields, numerous research efforts continue to make progress toward new therapeutic interventions for segmental bone loss, including novel biomaterial development as well as cell-based strategies. Despite an ever-evolving literature base of these new therapeutic and engineered options, there remains a disconnect with the clinical practice, with very few translating into clinical use. A symposium entitled "Building better bone: The weaving of biologic and engineering strategies for managing bone loss," was presented at the 2016 Orthopaedic Research Society Conference to further explore this engineering-clinical disconnect, by surveying basic, translational, and clinical researchers along with orthopaedic surgeons and proposing ideas for pushing the bar forward in the field of segmental bone loss. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1855-1864, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. The role of stromal cells in inflammatory bone loss.

    Science.gov (United States)

    Wehmeyer, C; Pap, T; Buckley, C D; Naylor, A J

    2017-07-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, local and systemic bone loss and a lack of compensatory bone repair. Fibroblast-like synoviocytes (FLS) are the most abundant cells of the stroma and a key population in autoimmune diseases such as RA. An increasing body of evidence suggests that these cells play not only an important role in chronic inflammation and synovial hyperplasia, but also impact bone remodelling. Under inflammatory conditions FLS release inflammatory cytokines, regulate bone destruction and formation and communicate with immune cells to control bone homeostasis. Other stromal cells, such as osteoblasts and terminally differentiated osteoblasts, termed osteocytes, are also involved in the regulation of bone homeostasis and are dysregulated during inflammation. This review highlights our current understanding of how stromal cells influence the balance between bone formation and bone destruction. Increasing our understanding of these processes is critical to enable the development of novel therapeutic strategies with which to treat bone loss in RA. © 2017 British Society for Immunology.

  18. Temporal bone imaging in osteogenesis imperfecta patients with hearing loss

    NARCIS (Netherlands)

    Swinnen, F.K.R.; Casselman, J.W.; Leenheer, E.M. De; Cremers, C.W.R.J.; Dhooge, I.J.

    2013-01-01

    OBJECTIVES/HYPOTHESIS: Osteogenesis imperfecta (OI) is an autosomal-dominant connective-tissue disorder, predominantly characterized by bone fragility. Conductive hearing loss develops in half of the OI patients and often progresses to mixed loss. Findings of computed tomography (CT) and magnetic

  19. Obesity Prevention and Weight Maintenance After Loss.

    Science.gov (United States)

    German, Alexander James

    2016-09-01

    Obesity is one of the most prevalent medical diseases in pets. Outcomes are often disappointing; many animals either fail to reach target weight or regain weight. This article discusses managing obesity, focusing on prevention. It gives guidance on establishing monitoring programs that use regular body weight and condition assessments to identify animals at risk of inappropriate weight gain, enabling early intervention. Weight management in obese animals is a lifelong process. Regular weight and body condition monitoring are key to identifying animals that rebound early, while continuing to feed a therapeutic weight loss diet can help prevent it from happening. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Bone loss after bariatric surgery: causes, consequences, and management.

    Science.gov (United States)

    Stein, Emily M; Silverberg, Shonni J

    2014-02-01

    Bariatric surgery is an effective and increasingly common treatment for severe obesity and its many comorbidities. The side-effects of bariatric surgery can include detrimental effects on bone and mineral metabolism. Bone disease in patients who have had bariatric surgery is affected by preoperative abnormalities in bone and mineral metabolism related to severe obesity. Changes that arise after bariatric surgery are specific to procedure type: the most pronounced abnormalities in calciotropic hormones and bone loss are noted after procedures that result in the most malabsorption. The most consistent site for bone loss after all bariatric procedures is at the hip. There are limitations of dual-energy x-ray absorptiometry technology in this population, including artefact introduced by adipose tissue itself. Bone loss after bariatric surgery is probably multifactorial. Proposed mechanisms include skeletal unloading, abnormalities in calciotropic hormones, and changes in gut hormones. Few data for fracture risk in the bariatric population are available, and this is a crucial area for additional research. Treatment should be geared toward correction of nutritional deficiencies and study of bone mineral density in high-risk patients. We explore the skeletal response to bariatric surgery, potential mechanisms for changes, and strategies for management. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Serum markers of bone metabolism show bone loss in hibernating bears

    Science.gov (United States)

    Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

    2003-01-01

    Disuse osteopenia was studied in hibernating black bears (Ursus americanus) using serum markers of bone metabolism. Blood samples were collected from male and female, wild black bears during winter denning and active summer periods. Radioimmunoassays were done to determine serum concentrations of cortisol, the carboxy-terminal cross-linked telopeptide, and the carboxy-terminal propeptide of Type I procollagen, which are markers of hone resorption and formation, respectively. The bone resorption marker was significantly higher during winter hibernation than it was in the active summer months, but the bone formation marker was unchanged, suggesting an imbalance in bone remodeling and a net bone loss during disuse. Serum cortisol was significantly correlated with the bone resorption marker, but not with the bone formation marker. The bone formation marker was four- to fivefold higher in an adolescent and a 17-year-old bear early in the remobilization period compared with the later summer months. These findings raise the possibility that hibernating black bears may minimize bone loss during disuse by maintaining osteoblastic function and have a more efficient compensatory mechanism for recovering immobilization-induced bone loss than that of humans or other animals.

  2. Prevention of perinatal loss: towards personalized medicine

    OpenAIRE

    Medvedev M.V.; Davydova Iu.V.

    2016-01-01

    The literature review on the prevention of preterm labor is carried out. Preterm labor is the actual problem of modern obstetrics due to the impact on maternal and child health. It is affects the level of perinatal morbidity, disability and infant mortality. Preterm labor occupies a dominant position in the structure of perinatal losses. Introduction of the prophylactic modern technologies of the preterm labor using micronized progesterone containing preparations allows clearly reduce their f...

  3. Regional cortical and trabecular bone loss after spinal cord injury.

    Science.gov (United States)

    Dudley-Javoroski, Shauna; Shields, Richard K

    2012-01-01

    Spinal cord injury (SCI) triggers rapid loss of trabecular bone mineral density (BMD) in bone epiphyses and a loss of cortical cross-sectional area (CSA) in bone diaphyses, increasing fracture risk for people with SCI. The purpose of this study was to measure trabecular BMD and cortical CSA loss at several previously unexamined lower-limb sites (4% fibula, 12% femur, 86% tibia, cortical) in individuals with SCI. Using peripheral quantitative computed tomography, we scanned 13 participants with SCI longitudinally and 16 on one occasion; 21 participants without SCI served as controls. In the first year post-SCI, 15% to 35% of BMD was lost at the distal femur, proximal tibia, and distal fibula. Bone loss at the distal fibula accelerated between 1 and 2 years post-SCI. BMD at these sites reached a steady state value of ~50% of the non-SCI value 4 years post-SCI. At the tibia diaphysis, cortical CSA decline was slower, eventually reaching 65% of the non-SCI value. Because of the extensive loss of bone observed at these sites, careful consideration needs to be given to the dose of musculoskeletal stress delivered during rehabilitation interventions like standing, muscle electrical stimulation, and aggressive stretching of spastic muscles.

  4. Effect of Cistanches Herba Aqueous Extract on Bone Loss in Ovariectomized Rat

    Directory of Open Access Journals (Sweden)

    Zaiguo Huang

    2011-08-01

    Full Text Available To assess the ability of traditional Chinese medicine Cistanches Herba extract (CHE to prevent bone loss in the ovariectomized (OVX rat, Cistanches Herba extract (CHE was administered intragastrically to the rats. Female rats were anesthetized with pentobarbital sodium (40 mg kg−1, i.p., and their ovaries were removed bilaterally. The rats in the sham-operated group were anesthetized, laparotomized, and sutured without removing their ovaries. After 1 week of recovery from surgery, the OVX rats were randomly divided into three groups and orally treated with H2O (OVX group or CHE (100 or 200 mg kg−1 daily for 3 months. The sham-operated group (n = 8 was orally treated with H2O. After 3 months, the total body bone mineral density (BMD, bone mineral content (BMC, Bone biomechanical index, blood mineral levels and blood antioxidant enzymes activities were examined in sham-operated, ovariectomized and Cistanches Herba extract treated rats. Results showed that Cistanches Herba extract treatment significantly dose-dependently enhanced bone mineral density (BMD, bone mineral content (BMC, maximum load, displacement at maximum load, stress at maximum load, load at auto break, displacement at auto break, and stress at auto break, and blood antioxidant enzymes activities, decreased blood Ca, Zn and Cu levels compared to the OVX group. This experiment demonstrates that the administration of Cistanches Herba extract to ovariectomized rats reverses bone loss and prevents osteoporosis.

  5. Polar bears (Ursus maritimus), the most evolutionary advanced hibernators, avoid significant bone loss during hibernation.

    Science.gov (United States)

    Lennox, Alanda R; Goodship, Allen E

    2008-02-01

    Some hibernating animals are known to reduce muscle and bone loss associated with mechanical unloading during prolonged immobilisation,compared to humans. However, here we show that wild pregnant polar bears (Ursus maritimus) are the first known animals to avoid significant bone loss altogether, despite six months of continuous hibernation. Using serum biochemical markers of bone turnover, we showed that concentrations for bone resorption are not significantly increased as a consequence of hibernation in wild polar bears. This is in sharp contrast to previous studies on other hibernating species, where for example, black bears (Ursus americanus), show a 3-4 fold increase in serum bone resorption concentrations posthibernation,and must compensate for this loss through rapid bone recovery on remobilisation, to avoid the risk of fracture. In further contrast to black bears, serum concentrations of bone formation markers were highly significantly increased in pregnant female polar bears compared to non-pregnant,thus non-hibernating females both prior to and after hibernation. However, bone formation concentrations in new mothers were significantly reduced compared to pre-hibernation concentrations. The de-coupling of bone turnover in favour of bone formation prior to hibernation, suggests that wild polar bears may posses a unique physiological mechanism for building bone in protective preparation against expected osteopenia associated with disuse,starvation, and hormonal drives to mobilise calcium for reproduction, during hibernation. Understanding this physiological mechanism could have profound implications for a natural solution for the prevention of osteoporosis in animals subjected to captivity with inadequate space for exercise,humans subjected to prolonged bed rest while recovering from illness, or astronauts exposed to antigravity during spaceflight.© 2008 Elsevier Inc. All rights reserved.

  6. Adjuvant bone-targeted therapy to prevent metastasis: lessons from the AZURE study.

    Science.gov (United States)

    Coleman, Robert E

    2012-09-01

    Bone-targeted treatments with bisphosphonates (e.g., zoledronic acid) and denosumab are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the 'vicious cycle' of growth factor and cytokine signalling between tumour and bone cells within the bone marrow microenvironment. In early stage breast cancer, treatment with zoledronic acid has shown improvements in disease-free and overall survival, notably in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease, treated with goserelin to suppress ovarian function. Other bisphosphonates such as clodronate may produce similar benefits. Additionally, in castrate-resistant prostate cancer, treatment with denosumab delays the development of bone metastases. These results strongly support the adjuvant use of bone-targeted treatments, but suggest that reproductive hormones are an important treatment modifier to take into account.

  7. Osteopenia in anorexia nervosa: specific mechanisms of bone loss.

    Science.gov (United States)

    Lennkh, C; de Zwaan, M; Bailer, U; Strnad, A; Nagy, C; el-Giamal, N; Wiesnagrotzki, S; Vytiska, E; Huber, J; Kasper, S

    1999-01-01

    Osteopenia is a well recognized medical complication of anorexia nervosa (AN). The mechanism of bone loss is not fully understood and there is uncertainty about its management. New markers of bone turnover have been developed. C-terminal type 1 propeptide (PICP) is a measure of bone formation and urinary pyridinolines such as deoxypyridinoline (DPYRX) and serum carboxyterminal crosslinked telopeptide (ICTP) are markers of bone resorption. The aim of this study was to examine these bone markers in patients with AN. Twenty female patients with AN and 12 healthy controls were included in the study. Bone mineral density (BMD) of AN patients was measured by dual energy X-ray absorptiometry (DEXA). Lumbar bone density was significantly reduced in the AN group compared to standardised values of thirty year old adults (t-score 83.2%, S.D. 12.1). Femoral neck bone density showed an even greater reduction (t-score 79.4%, S.D. 13.5). We found a significant negative correlation between femoral BMD and the duration of the illness. Femoral BMD correlated significantly with minimal body weight (r(16) = 0.504, p = 0.033). The markers of bone resorption were significantly higher in the patients with AN compared to the values of the control group (ICTP t(30) = -2.15, p = 0.04, DPYRX t(25) = -2.26, p = 0.033), whereas the markers of bone formation did not differ significantly between the groups. AN appears to be a low turn over state associated with increased bone resorption without concomitant bone formation. This pattern differs from osteopenia in menopausal women and should, therefore, lead to the development of specific therapeutic strategies in AN associated osteopenia. Hormone replacement therapy as well as calcium and vitamine D-supplementation are so far discussed controversially. Long-term treatment studies are warranted.

  8. Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats

    Science.gov (United States)

    Summary: Studies suggest that green tea polyphenols (GTP) or alphacalcidol is promising agent for preventing bone loss. Findings that GTP supplementation in the drinking water plus alphacalcidol administration resulted in increased bone mass via a decrease of oxidative stress and inflammation sugges...

  9. A multi-method assessment of bone maintenance and loss in an Imperial Roman population: Implications for future studies of age-related bone loss in the past.

    Science.gov (United States)

    Beauchesne, Patrick; Agarwal, Sabrina C

    2017-09-01

    One of the hallmarks of contemporary osteoporosis and bone loss is dramatically higher prevalence of loss and fragility in females post-menopause. In contrast, bioarchaeological studies of bone loss have found a greater diversity of age- and sex-related patterns of bone loss in past populations. We argue that the differing findings may relate to the fact that most studies use only a single methodology to quantify bone loss and do not account for the heterogeneity and complexity of bone maintenance across the skeleton and over the life course. We test the hypothesis that bone mass and maintenance in trabecular bone sites versus cortical bone sites will show differing patterns of age-related bone loss, with cortical bone sites showing sex difference in bone loss that are similar to contemporary Western populations, and trabecular bone loss at earlier ages. We investigated this hypothesis in the Imperial Roman population of Velia using three methods: radiogrammetry of the second metacarpal (N = 71), bone histology of ribs (N = 70), and computerized tomography of trabecular bone architecture (N = 47). All three methods were used to explore sex and age differences in patterns of bone loss. The suite of methods utilized reveal differences in the timing of bone loss with age, but all methods found no statistically significant differences in age-related bone loss. We argue that a multi-method approach reduces the influence of confounding factors by building a reconstruction of bone turnover over the life cycle that a limited single-method project cannot provide. The implications of using multiple methods beyond studies of bone loss are also discussed. © 2017 Wiley Periodicals, Inc.

  10. Bone loss rate in adrenal incidentalomas: a longitudinal study.

    Science.gov (United States)

    Chiodini, I; Torlontano, M; Carnevale, V; Guglielmi, G; Cammisa, M; Trischitta, V; Scillitani, A

    2001-11-01

    Although by definition patients with adrenal incidentalomas (AI) do not have evident clinical syndromes, they may frequently suffer from subclinical hypercortisolism (SH). This is of some importance because of evidence that SH may lead to clinical complications, including bone loss. Thus, the understanding of bone involvement due to SH may be extremely important in the management of AI. Unfortunately, the available data on bone mineral density (BMD) in AI patients come from cross-sectional studies, which, to further complicate our understanding, are also conflicting, probably due to a different selection of patients and/or the variability in cortisol secretion (CS) often described in AI. To gain further insight about this topic, we performed a longitudinal study evaluating the rate of spinal and femoral bone loss levels in 24 females with AI. AI subjects were subdivided in two groups on the basis of the median of urinary cortisol secretion (UFC): group I (n = 12; UFC, 140.4 nmol/24 h). Spinal BMD was measured by both single energy quantitative computed tomography (L1-L4) and dual energy x-ray absorptiometry (DXA; L2-L4), and femoral BMD was determined by DXA. Bone loss rate was expressed as the change in z-score per yr. The spinal bone loss rate was higher (P < 0.005) in group II than in group I when measured by both quantitative computed tomography (-0.19 +/- 0.14 vs. 0.00 +/- 0.15) and DXA (-0.19 +/- 0.17 vs. 0.00 +/- 0.11). Moreover, CS and spinal bone loss rate were significantly correlated when patients were considered together. In conclusion, our data show that 1) AI patients with higher CS have increased lumbar trabecular bone loss rate than those with lower CS; and 2) the degree of spinal bone loss rate is related to the degree of CS. Thus, lumbar spine (LS) BMD has to be evaluated for well balanced decision-making on the treatment of choice for AI female patients.

  11. The current state of bone loss research: data from spaceflight and microgravity simulators.

    Science.gov (United States)

    Nagaraja, Mamta Patel; Risin, Diana

    2013-05-01

    Bone loss is a well documented phenomenon occurring in humans both in short- and in long-term spaceflights. This phenomenon can be also reproduced on the ground in human and animals and also modeled in cell-based analogs. Since space flights are infrequent and expensive to study the biomedical effects of microgravity on the human body, much of the known pathology of bone loss comes from experimental studies. The most commonly used in vitro simulators of microgravity are clinostats while in vivo simulators include the bed rest studies in humans and hindlimb unloading experiments in animals. Despite the numerous reports that have documented bone loss in wide ranges in multiple crew members, the pathology remains a key concern and development of effective countermeasures is still a major task. Thus far, the offered modalities have not shown much success in preventing or alleviating bone loss in astronauts and cosmonauts. The objective of this review is to capture the most recent research on bone loss from spaceflights, bed rest and hindlimb unloading, and in vitro studies utilizing cellular models in clinostats. Additionally, this review offers projections on where the research has to focus to ensure the most rapid development of effective countermeasures. Copyright © 2012 Wiley Periodicals, Inc.

  12. Rapid cortical bone loss in patients with chronic kidney disease.

    Science.gov (United States)

    Nickolas, Thomas L; Stein, Emily M; Dworakowski, Elzbieta; Nishiyama, Kyle K; Komandah-Kosseh, Mafo; Zhang, Chiyuan A; McMahon, Donald J; Liu, Xiaowei S; Boutroy, Stephanie; Cremers, Serge; Shane, Elizabeth

    2013-08-01

    Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2 to 5D, we used dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (range 0.9 to 4.3 years); bone changes were annualized and compared with baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: -1.3% (95% confidence interval [CI] -2.1 to -0.6) and -2.4% (95% CI -4.0 to -0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density, and thickness and increases in porosity: -2.9% (95% CI -3.7 to -2.2), -1.3% (95% CI -1.6 to -0.6), -2.8% (95% CI -3.6 to -1.9), and +4.2% (95% CI 2.0 to 6.4), respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates. Copyright © 2013 American Society for Bone and Mineral Research.

  13. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wactawski-Wende, Jean

    1998-01-01

    ... and oral bone loss, periodontal disease and tooth loss. We hypothesize that reduction in bone density leading to osteoporosis, plays a significant role in increasing susceptibility to destructive periodontitis and tooth loss...

  14. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wactawski-Wende, Jean

    2001-01-01

    ... and oral bone loss, periodontal disease and tooth loss. We hypothesize that reduction in bone density leading to osteoporosis, plays a significant role in increasing susceptibility to destructive periodontitis and tooth loss...

  15. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wacawski-Wende, Jean

    1997-01-01

    ... and oral bone loss, periodontal disease and tooth loss. We hypothesize that reduction in bone density leading to osteoporosis, plays a significant role in increasing susceptibility to destructive periodontitis and tooth loss...

  16. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wactawski-Wende, Jean

    1999-01-01

    ... and oral bone loss, periodontal disease and tooth loss. We hypothesize that reduction in bone density leading to osteoporosis, plays a significant role in increasing susceptibility to destructive periodontitis and tooth loss...

  17. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wactawski-Wende, Jean

    2000-01-01

    ... and oral bone loss, periodontal disease and tooth loss. We hypothesize that reduction in bone density leading to osteoporosis, plays a significant role in increasing susceptibility to destructive periodontitis and tooth loss...

  18. Staged subtalar fusion for severe calcaneus fractures with bone loss.

    Science.gov (United States)

    Williams, Chad G; Coffey, Michael J; Shorten, Peter; Lyions, James D; Laughlin, Richard T

    2013-01-01

    With high energy fractures to the calcaneus there is the potential for significant bone loss. The loss of bone can make it difficult to fully regain calcaneal alignment. In addition these fractures are often associated with significant soft tissue injury. These two factors make it difficult to address this injury in a single stage, and can have significant complications. To address these issues our initial goal in treatment has been restoration of calcaneal alignment and stabilization of the surrounding soft tissue, followed by delayed/staged subtalar arthrodesis. Patients with calcaneus fractures treated by a single surgeon from 2002 to 2012 were reviewed. Injuries which were found to have medial extrusion of the posterior facet and bone loss, and subsequently underwent a staged protocol involving early provisional fixation and late subtalar fusion were included. We treated 6 calcaneus fractures with bone loss. All patients were treated with staged subtalar fusion after initial irrigation and debridement and provisional fixation. No soft-tissue complications were noted after the fusion procedure in any of the six cases. Fusion occurred in all six patients at an average of 20.6 weeks (range, 13-23 weeks). All patients were able to ambulate and wear a regular shoe by one year following the initial injury. It is important in the high energy calcaneus fracture to assess for both soft tissue integrity and bone loss. A thorough debridement of both the soft tissues and any devitalized bone should be performed as well as provisional fixation which attempts to restore near normal calcaneal anatomy. Definitive fusion should not be performed until the soft tissues have fully recovered.

  19. Prevention of perinatal loss: towards personalized medicine

    Directory of Open Access Journals (Sweden)

    Medvedev M.V.

    2016-03-01

    Full Text Available The literature review on the prevention of preterm labor is carried out. Preterm labor is the actual problem of modern obstetrics due to the impact on maternal and child health. It is affects the level of perinatal morbidity, disability and infant mortality. Preterm labor occupies a dominant position in the structure of perinatal losses. Introduction of the prophylactic modern technologies of the preterm labor using micronized progesterone containing preparations allows clearly reduce their frequency in a number of clinics that use the destination progesterone protocol for ultrasound cervical length less than 25 mm, as well as in women with preterm labor in history.

  20. Systemic Administration of Allogeneic Mesenchymal Stem Cells Does Not Halt Osteoporotic Bone Loss in Ovariectomized Rats.

    Directory of Open Access Journals (Sweden)

    Shuo Huang

    demonstrated that systemic administration of allogenic MSCs had no obvious effect on osteoporotic bone loss in OVX rats when using the cells from the same donor; and repeated injection of allogeneic MSCs from different donors might promote bone loss in OVX rats. These findings indicate that despite allogenic MSCs systemic infusion is safe, their administration alone may not be an effective mean for preventing osteoporotic bone loss.

  1. Soy Isoflavones and Osteoporotic Bone Loss: A Review with an Emphasis on Modulation of Bone Remodeling

    Science.gov (United States)

    Zheng, Xi; Lee, Sun-Kyeong

    2016-01-01

    Abstract Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans. PMID:26670451

  2. Bone transport and compression-distraction in the treatment of bone loss of the lower limbs.

    Science.gov (United States)

    Lavini, Franco; Dall'Oca, Carlo; Bartolozzi, Pietro

    2010-11-01

    A clinical series of 17 adult patients operated due to significant by bone loss of the long bones of the lower extremity (3 femurs and 11 tibias), is presented. Their management consisted of 6 bone transports (6 tibias) and 11 compression distraction procedures (3 femurs and 8 tibiae) using monolateral external fixators. Bone loss ranged from 3.9 cm to 14.7 cm. Mean healing time was 301 days with a mean healing index of 45.6 days for cm of lengthening achieved. The clinical and radiological results were excellent in 9, good in 6 and fair in 2 patients according to the utilised criteria of assessment. Consolidation was achieved in all but one patient who developed an aseptic stiff non-union. Two patients developed residual limb-length discrepancy less than 1.5 cm, three tibias ended up with less than 5° of valgus deviation. In two cases the half-pins were re-inserted due to early loosening. In two cases reoperation was needed for late bending of the callus after fixator removal. Three cases of bone transport and 1 case of compression distraction needed bone grafting at the docking site. Bone transport and compression-distraction are effective methods for treating bone loss in the lower extremity. It is suggested that the compression-distraction technique is preferable, since this is associated with a lower incidence of complications than bone transport procedures. The deciding factor, however, is the actual extent of the bone loss. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss.

    Science.gov (United States)

    Harre, Ulrike; Lang, Stefanie C; Pfeifle, René; Rombouts, Yoann; Frühbeißer, Sabine; Amara, Khaled; Bang, Holger; Lux, Anja; Koeleman, Carolien A; Baum, Wolfgang; Dietel, Katharina; Gröhn, Franziska; Malmström, Vivianne; Klareskog, Lars; Krönke, Gerhard; Kocijan, Roland; Nimmerjahn, Falk; Toes, René E M; Herrmann, Martin; Scherer, Hans Ulrich; Schett, Georg

    2015-03-31

    Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss.

  4. Correlation of interdental and interradicular bone loss in patients ...

    African Journals Online (AJOL)

    2012-01-19

    Jan 19, 2012 ... Key words: Alveolar bone loss, chronic periodontitis, dental, furcation defect, radiography. Date of Acceptance: 19-Jan- ... cemento-enamel junction (CEJ) and the alveolar crest (AC) or the bottom of the bony ..... prognosis of periodontal healing of infrabony defects: Two different definitions of defect depth.

  5. Mandibular atrophy and metabolic bone loss. Endocrinology, radiology and histomorphometry

    NARCIS (Netherlands)

    Habets, L. L.; Bras, J.; Borgmeyer-Hoelen, A. M.

    1988-01-01

    In 11 edentulous patients with a severe atrophy of the mandible and submitted for ridge augmentation, endocrinological, radiological and histomorphometrical studies were carried out. The results showed that metabolic bone loss, histologically in nearly all patients characterized as a disturbance in

  6. Interleukin-1 is essential for systemic inflammatory bone loss.

    NARCIS (Netherlands)

    Polzer, K.; Joosten, L.A.B.; Gasser, J.; Distler, J.H.; Ruiz, G.; Baum, W.; Redlich, K.; Bobacz, K.; Smolen, J.S.; Berg, W. van den; Schett, G.; Zwerina, J.

    2010-01-01

    OBJECTIVES: Chronic inflammation is a major risk factor for systemic bone loss leading to osteoporotic fracture and substantial morbidity and mortality. Inflammatory cytokines, particularly tumour necrosis factor (TNF) and interleukin-1 (IL1), are thought to play a key role in the pathogenesis of

  7. Patterns of bone loss around teeth restored with endodontic posts

    NARCIS (Netherlands)

    Katsamakis, S.; Timmerman, M.; van der Velden, U.; de Cleen, M.; van der Weijden, F.

    2009-01-01

    Objectives: This retrospective study described the pattern of bone loss around teeth with endodontic posts in periodontitis patients, and compared it with contra-lateral teeth without posts. Material and Methods: From full-mouth radiographic surveys of 146 periodontitis patients (35 years), 194

  8. Correlation of interdental and interradicular bone loss in patients ...

    African Journals Online (AJOL)

    Objective: The aim of this study was to investigate the correlation between interdental and interradicular bone loss and clinical parameters in patients with chronic periodontitis. Materials and Methods: One hundred-twenty intraoral periapical radiographs of first molars were obtained from patients with chronic periodontitis ...

  9. Rate of bone loss in postmenopausal and osteoporotic women

    International Nuclear Information System (INIS)

    Aloia, J.F.; Ross, P.; Vaswani, A.; Zanzi, I.; Cohn, S.H.

    1982-01-01

    Regional and total bone mass were determined in three groups of women by photon absorptiometry of the distal radius [bone mineral content (BMC)] and total neutron activation analysis [total body calcium (TBCa)], respectively. There were three groups of patients: group A, osteoporotic women treated with a variety of pharmacologic agents; group B, osteoporotic women (controls) taking only calcium supplements; and group C, normal postmenopausal women. The mean TBCa and BMC were considerably higher in the postmenopausal women than in the osteoporotic women. The rate of change of bone mass in group C was -0.45%/yr and -0.9%/yr for the total skeleton and radius, respectively. Group B had no significant rate of loss, whereas group A demonstrated a significant increase in TBCa of 0.75%/yr with no change in the BMC of the radius. There were no significant between-subject correlations for the slopes (rates of change) of the two bone mineral measurements

  10. Bone growth stimulators. New tools for treating bone loss and mending fractures.

    Science.gov (United States)

    Whitfield, James F; Morley, Paul; Willick, Gordon E

    2002-01-01

    In the new millennium, humans will be traveling to Mars and eventually beyond with skeletons that respond to microgravity by self-destructing. Meanwhile in Earth's aging populations growing numbers of men and many more women are suffering from crippling bone loss. During the first decade after menopause all women suffer an accelerating loss of bone, which in some of them is severe enough to result in "spontaneous" crushing of vertebrae and fracturing of hips by ordinary body movements. This is osteoporosis, which all too often requires prolonged and expensive care, the physical and mental stress of which may even kill the patient. Osteoporosis in postmenopausal women is caused by the loss of estrogen. The slower development of osteoporosis in aging men is also due at least in part to a loss of the estrogen made in ever smaller amounts in bone cells from the declining level of circulating testosterone and is needed for bone maintenance as it is in women. The loss of estrogen increases the generation, longevity, and activity of bone-resorbing osteoclasts. The destructive osteoclast surge can be blocked by estrogens and selective estrogen receptor modulators (SERMs) as well as antiosteoclast agents such as bisphosphonates and calcitonin. But these agents stimulate only a limited amount of bone growth as the unaffected osteoblasts fill in the holes that were dug by the now suppressed osteoclasts. They do not stimulate osteoblasts to make bone--they are antiresorptives not bone anabolic agents. (However, certain estrogen analogs and bisphosphates may stimulate bone growth to some extent by lengthening osteoblast working lives.) To grow new bone and restore bone strength lost in space and on Earth we must know what controls bone growth and destruction. Here we discuss the newest bone controllers and how they might operate. These include leptin from adipocytes and osteoblasts and the statins that are widely used to reduce blood cholesterol and cardiovascular damage. But

  11. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wactawski-Wende, Jean

    2000-01-01

    The overall purpose of this study is to determine the relationship between skeletal and oral bone density, identify factors influencing bone loss, and determine the relationship between osteoporosis...

  12. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wactawski-Wende, Jean

    1999-01-01

    The overall purpose of this study is to determine the relationship between skeletal and oral bone density, identify factors influencing bone loss, and determine the relationship between osteoporosis...

  13. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wactawski-Wende, Jean

    2001-01-01

    The overall purpose of this study is to determine the relationship between skeletal and oral bone density, identify factors influencing bone loss, and determine the relationship between osteoporosis...

  14. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wactawski-Wende, Jean

    1998-01-01

    The overall purpose of this study is to determine the relationship between skeletal and oral bone density, identify factors influencing bone loss, and determine the relationship between osteoporosis...

  15. Risk Factors for Osteoporosis and Oral Bone Loss in Postmenopausal Women

    National Research Council Canada - National Science Library

    Wacawski-Wende, Jean

    1997-01-01

    The overall purpose of this study is to determine the relationship between skeletal and oral bone density, identify factors influencing bone loss, and determine the relationship between osteoporosis...

  16. CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.

    Science.gov (United States)

    Rodríguez-Sanz, M; García-Giralt, N; Prieto-Alhambra, D; Servitja, S; Balcells, S; Pecorelli, R; Díez-Pérez, A; Grinberg, D; Tusquets, I; Nogués, X

    2015-08-01

    Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (Pbone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss. © 2015 Society for Endocrinology.

  17. Sclerostin Antibody Reverses Bone Loss by Increasing Bone Formation and Decreasing Bone Resorption in a Rat Model of Male Osteoporosis.

    Science.gov (United States)

    Li, Xiaodong; Ominsky, Michael S; Villasenor, Kelly S; Niu, Qing-Tian; Asuncion, Frank J; Xia, Xuechun; Grisanti, Mario; Wronski, Thomas J; Simonet, W Scott; Ke, Hua Zhu

    2018-01-01

    Sclerostin antibody (Scl-Ab) restored bone mass and strength in the ovariectomized rat model of postmenopausal osteoporosis. Increased bone mineral density (BMD) and decreased skeletal fragility fracture risk have been reported in postmenopausal osteoporotic women receiving Scl-Ab. In males, loss of androgen leads to rapid decreases in BMD and an increased risk of fragility fractures. We hypothesized that Scl-Ab could reverse the loss of bone mass and strength caused by androgen ablation in the orchiectomized (ORX) rat model of male osteoporosis. We treated 9-month-old ORX Sprague Dawley rats (3 months after ORX) subcutaneously twice weekly with vehicle or Scl-Ab (5 or 25 mg/kg) for 6 weeks (n = 10 per group). Both doses of Scl-Ab fully reversed the BMD deficit in the lumbar spine and femur and tibia in ORX rats. Microcomputed tomography showed that the bone mass in the fifth lumbar vertebral body, femur diaphysis, and femoral neck were dose-dependently restored by Scl-Ab. The bone strength at these sites increased significantly with Scl-Ab to levels matching those of sham-operated controls and correlated positively with improvements in bone mineral content, demonstrating bone quality maintenance. Dynamic histomorphometry of the tibial diaphysis and second lumbar vertebral body demonstrated that Scl-Ab significantly increased bone formation on periosteal, endocortical, and trabecular surfaces and significantly decreased bone resorption on endocortical and trabecular surfaces. The effects of Scl-Ab on increasing bone formation and decreasing bone resorption led to restoration of bone mass and strength in androgen-deficient rats. These findings support the ongoing evaluation of Scl-Ab as a potential therapeutic agent for osteoporosis in men. Copyright © 2018 Endocrine Society.

  18. Structural joint damage and hand bone loss in patients with rheumatoid arthritis.

    Science.gov (United States)

    Lykke, Midtbøll Ørnbjerg

    2018-03-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by pain, swelling and progressive destruction of the joints leading to loss of function and invalidity. The bone destruction in RA is characterised by two distinct features: structural joint damage and hand bone loss, and their prevention is an important treatment goal. Inhibitors of tumour necrosis factor alpha (TNF-inhibitors) have markedly improved the treatment options in RA patients who fail treatment with conventional synthetic Disease Modifying Anti Rheumatic Drugs (sDMARDS), but their effectiveness with regards to structural joint damage and hand bone loss, predictors thereof and the association with disease activity during treatment have mainly been investigated in randomized controlled trials (RCTs) with limited generalizability due to strict in- and exclusion criteria.
 The main aim of the PhD thesis was to assess and predict structural joint damage and hand bone loss in patients with early and established RA treated with sDMARDs and TNF-inhibitors. This was investigated in two cohorts: A) The "DANBIO X-ray study": an observational, nationwide, longitudinal cohort study of established RA patients treated in clinical practice who initiated TNF-inhibitor treatment after failure of sDMARDs and B) The "OPERA study": a randomized controlled trial of sDMARD-naïve patients with early RA treated with methotrexate (MTX) and intraarticular glucocorticoid injections in combination with adalimumab or placebo-adalimumab. Structural joint damage progression was assessed with the Sharp/van der Heijde radiographic method and hand bone loss was assessed with Digital X-ray Radiogrammetry. 
From the studies presented in the PhD thesis the following was concluded:
 Structural joint damage progression and hand bone loss were significantly lower during two years of TNF-inhibitor treatment compared to the previous two years of sDMARD-treatment in the DANBIO X-ray Study. The majority of patients had

  19. Proximal alveolar bone loss in a longitudinal radiographic investigation

    International Nuclear Information System (INIS)

    Bolin, A.; Lavstedt, S.; Henrikson, C.O.; Frithiof, L.

    1986-01-01

    The difference in proximal alveolar bone height between 1970 and 1980, the ''ABD index'', has been measured longitudinally in radiographs from an unselected material. The group constitutes 406 individuals born in 1904 - 1952 in the county of Stockholm. 13 of 18 predictors determined in 1970 were significantly related to the ABD index in the simple correlation analyses. The predictor ''the alveolar bone loss 1970'' (ABL index 1970) had the strongest correlation to the ABD index. In the stepwise multiple regression analysis the predictor ABL index 1970 and three other predictors reached significant levels. These were age, number of lost teeth and Russell's Periodontal Index

  20. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation.

    Science.gov (United States)

    Fan, Ruoxun; Gong, He; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone.

  1. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

    Directory of Open Access Journals (Sweden)

    Ruoxun Fan

    2016-01-01

    Full Text Available The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone.

  2. Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss.

    Science.gov (United States)

    Yuan, X; Cao, J; Liu, T; Li, Y-P; Scannapieco, F; He, X; Oursler, M J; Zhang, X; Vacher, J; Li, C; Olson, D; Yang, S

    2015-12-01

    Regulators of G protein signaling (Rgs) have pivotal roles in controlling various cellular processes, such as cell differentiation. How Rgs proteins regulate osteoclast (OC) differentiation, function and bone homeostasis is poorly understood. It was previously demonstrated that Rgs12, the largest protein in the Rgs family, is predominantly expressed in OCs and regulates OC differentiation in vitro. To further understand the role and mechanism of Rgs12 in OC differentiation and bone diseases in vivo, we created OC-targeted Rgs12 knockout mice by using inducible Mx1-Cre and CD11b-Cre. Deletion of Rgs12 in hematopoietic cells or specifically in OC precursors resulted in increased bone mass with decreased OC numbers. Loss of Rgs12 impaired OC differentiation and function with impaired Ca(2+) oscillations and reduced nuclear factor of activated T cells (NFAT) 2 expression. The introduction of wild-type osteoblasts did not rescue the defective osteoclastogenesis. Ectopic expression of NFAT2 rescued defective OC differentiation in CD11b;Rgs12(fl/fl) cells and promoted normal OC differentiation. Moreover, deletion of Rgs12 significantly inhibited pathological osteoclastogenesis and bone destruction in Rgs12-deficient mice that were subjected to ovariectomy and lipodysaccharide for bone loss. Thus our findings demonstrate that Rgs12 is an important regulator in OC differentiation and function and identify Rgs12 as a potential therapeutic target for osteoporosis and inflammation-induced bone loss.

  3. Alpha-1 Antitrypsin Gene Therapy Ameliorates Bone Loss in Ovariectomy-Induced Osteoporosis Mouse Model.

    Science.gov (United States)

    Akbar, Mohammad Ahsanul; Cao, Jay J; Lu, Yuanqing; Nardo, David; Chen, Mong-Jen; Elshikha, Ahmed S; Ahamed, Rubina; Brantly, Mark; Holliday, L Shannon; Song, Sihong

    2016-09-01

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at menopause. Therefore, anti-inflammatory strategies hold a great potential for the prevention of postmenopausal osteoporosis. In this study, we investigated the effect of gene therapy of recombinant adeno-associated virus (rAAV)-mediated human alpha-1 antitrypsin (hAAT), a multifunctional protein that has anti-inflammatory property, on bone loss in an ovariectomy-induced osteoporosis mouse model. Adult ovariectomized (OVX) mice were intraperitoneally (i.p.) injected with hAAT (protein therapy), rAAV8-CB-hAAT (gene therapy), or phosphate buffer saline (PBS). Age-matched and sham-operated animals were used as controls. Eight weeks after the treatment, animals were sacrificed and bone-related biomarkers and vertebral bone structure were evaluated. Results showed that hAAT gene therapy significantly decreased serum IL-6 level and receptor activator of NF-κB (RANK) gene expression in bone. Importantly, hAAT gene therapy increased bone volume/total volume and decreased structure model index (SMI) compared to PBS injection in OVX mice. These results demonstrate that hAAT gene therapy by rAAV vector efficiently mitigates bone loss possibly through inhibition of proinflammatory cytokine IL-6 and RANK gene expression. Considering the safety profile of hAAT and rAAV vector in humans, our results provide a new alternative for the treatment of osteoporosis.

  4. Dihydromyricetin Protects against Bone Loss in Ovariectomized Mice by Suppressing Osteoclast Activity

    Directory of Open Access Journals (Sweden)

    Libo Zhao

    2017-12-01

    Full Text Available Dihydromyricetin (DMY, the main flavonoid component of Ampelopsis grossedentata, possesses pharmacological activities useful for treatment of diseases associated with inflammation and oxidative damage. Because osteoclasts are often involved in chronic low-grade systemic inflammation and oxidative damage, we hypothesized that DMY may be an effective treatment for osteoclast-related diseases. The effects of DMY on osteoclast formation and activity were examined in vitro. Female C57BL/6 mice were ovariectomized to mimic menopause-induced bone loss and treated with DMY, and femur samples were subjected to bone structure and histological analysis, serum biochemical indicators were also measured. DMY suppressed the activation of nuclear factor-κB, c-Fos and mitogen-activated protein kinase, and prevented production of reactive oxygen species. DMY decreased expression of osteoclast-specific genes, including Trap, Mmp-9, Cathepsin K, C-Fos, Nfatc1, and Rank. In addition, DMY prevented bone loss and decreased serum levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6, and with a decrease in the ratio between receptor activator of nuclear factor-κB (RANK ligand (RANKL and osteoprotegerin (OPG in vivo. These findings demonstrate that DMY attenuates bone loss and inhibits osteoclast formation and activity through modulation of multiple pathways both upstream and downstream of RANKL signaling. DMY may thus be a useful option for treatment of osteoclast-related diseases such as rheumatoid arthritis and osteoporosis.

  5. Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

    2016-09-15

    This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

  6. Dietary phosphorus exacerbates bone loss induced by cadmium in ovariectomized rats.

    Science.gov (United States)

    Bakhshalian, Neema; Johnson, Sarah A; Hooshmand, Shirin; Feresin, Rafaela G; Elam, Marcus L; Soung, Do Y; Payton, Mark E; Arjmandi, Bahram H

    2014-12-01

    Postmenopausal bone loss can be exacerbated by environmental contaminants, including the heavy metal cadmium (Cd). We hypothesized that incorporating phosphorus (P) into the diet would lead to the chelation of Cd into P, preventing its absorption and subsequent bone loss. To test this hypothesis, we used ovariectomized rats as a model of postmenopausal osteoporosis to examine the deleterious effects of Cd on bone with and without added P. Fifty 3-month-old ovariectomized Sprague-Dawley rats were assigned to five treatment groups (n = 10 per group) for 3 months as follows: (1) control; (2) 50 ppm Cd; (3) 50 ppm Cd plus 1.2% P; (4) 200 ppm Cd; and (5) 200 ppm Cd plus 1.2% P. Cd plus P caused a significant loss of whole body (P = 0.0001 and P properties, 50 ppm Cd plus 1.2% P caused an increase in trabecular separation, whereas 200 ppm Cd plus 1.2% P caused a decrease in bone volume-to-total volume ratio, a decrease in trabecular number, and an increase in trabecular separation and structural model index. Our findings indicate that Cd exposure, along with high intake of P, may be a public health hazard with respect to bone health.

  7. Simulating Bone Loss in Microgravity Using Mathematical Formulations of Bone Remodeling

    Science.gov (United States)

    Pennline, James A.

    2009-01-01

    Most mathematical models of bone remodeling are used to simulate a specific bone disease, by disrupting the steady state or balance in the normal remodeling process, and to simulate a therapeutic strategy. In this work, the ability of a mathematical model of bone remodeling to simulate bone loss as a function of time under the conditions of microgravity is investigated. The model is formed by combining a previously developed set of biochemical, cellular dynamics, and mechanical stimulus equations in the literature with two newly proposed equations; one governing the rate of change of the area of cortical bone tissue in a cross section of a cylindrical section of bone and one governing the rate of change of calcium in the bone fluid. The mechanical stimulus comes from a simple model of stress due to a compressive force on a cylindrical section of bone which can be reduced to zero to mimic the effects of skeletal unloading in microgravity. The complete set of equations formed is a system of first order ordinary differential equations. The results of selected simulations are displayed and discussed. Limitations and deficiencies of the model are also discussed as well as suggestions for further research.

  8. Management of metaphyseal bone loss in revision knee arthroplasty.

    Science.gov (United States)

    Mancuso, Francesco; Beltrame, Arianna; Colombo, Elia; Miani, Enrick; Bassini, Fabrizio

    2017-06-07

    Revision total knee arthroplasty (TKA) is usually made more complex by the presence of bone defects, which may be caused by periprosthethic infection, polyethylene wear, implant loosening or fractures. The main aim of the present work is to review the available literature to understand the current options to manage with the bone loss during knee revisions. Available English literature for bone defects in revision TKAs has been evaluated looking at treatment options and their results in terms of clinical and radiological outcomes and failure rates. Anderson Orthopaedic Research Institute (AORI) classification is the most frequently used because it helps in the choice of the most suitable treatment. Several options are available in the management of metaphyseal bone loss in revision knee arthroplasty. For small and contained defects (AORI type 1) cement with or without screws and auto- or allograft morcellized bone are available. In uncontained but mild defects (AORI type 2A) metal augments should be use while large and uncontained defects (AORI type 2B and 3) are best addressed with structural allograft or metal filling devices (cones and sleeves). Stemmed components, either cemented or cementless, are recommended to reduce the strain at the interface implant-host. The treatment of bone defects in revision TKAs has evolved during the last years providing different options with good results at a short/medium term follow up. With the increasing revision burden, further scientific evidence is requested to identify the best approach for each patient. Long-term clinical outcome as well as implant survival after revision TKA are still sub-optimal and depend upon many factors including cause for revision, surgical approach, type of implants used and various patient factors.

  9. Basis of bone metabolism around dental implants during osseointegration and peri-implant bone loss.

    Science.gov (United States)

    Insua, Angel; Monje, Alberto; Wang, Hom-Lay; Miron, Richard J

    2017-07-01

    Despite the growing number of publications in the field of implant dentistry, there are limited studies to date investigating the biology and metabolism of bone healing around dental implants and their implications in peri-implant marginal bone loss. The aim of this review article is to provide a thorough understanding of the biological events taking place during osseointegration and the subsequent early and late phases of bone remodeling around dental implants. An update on the coupling mechanism occurring during bone resorption-bone remodeling is provided, focused on the relevance of the osteocytes, bone lining cells and immune cells during bone maintenance. An electronic and manual literature search was conducted by three independent reviewers in several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register databases for articles up to September 2016 with no language restriction. Local bone metabolism is subject to signals from systemic calcium-phosphate homeostasis and bone remodeling. Three areas of interest were reviewed due to recent reported compromises in bone healing including the putative effects of (1) cholesterol, (2) hyperlipidemia, and (3) low vitamin D intake. Moreover, the prominent influence of osteocytes and immune cells is discussed as being key regulators during dental implant osseointegration and maintenance. These cells are of crucial importance in the presence of biofilm accumulation and their associated byproducts that leads to hard and soft tissue breakdown; the so called peri-implantitis. Factors that could negatively impact osteoclastogenesis or osteal macrophage activation should be monitored in future research including implant placement/torque protocols, bone characteristics, as well as meticulous maintenance programs to favor osseointegration and future long-term stability and success of dental implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res

  10. Bone loss and human adaptation to lunar gravity

    Science.gov (United States)

    Keller, T. S.; Strauss, A. M.

    1992-01-01

    Long-duration space missions and establishment of permanently manned bases on the Moon and Mars are currently being planned. The weightless environment of space and the low-gravity environments of the Moon and Mars pose an unknown challenge to human habitability and survivability. Of particular concern in the medical research community today is the effect of less than Earth gravity on the human skeleton, since the limits, if any, of human endurance in low-gravity environments are unknown. This paper provides theoretical predictions on bone loss and skeletal adaptation to lunar and other nonterrestrial-gravity environments based upon the experimentally derived relationship, density approximately (mass x gravity)(exp 1/8). The predictions are compared to skeletal changes reported during bed rest, immobilization, certrifugation, and spaceflight. Countermeasures to reduce bone losses in fractional gravity are also discussed.

  11. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats.

    Science.gov (United States)

    Grubbe, M-C; Thomsen, J S; Nyengaard, J R; Duruox, M; Brüel, A

    2014-12-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind limb. Sixty female Wistar rats, 14 weeks old, were divided into the following groups: baseline, controls, BTX, BTX+GH, and GH. GH was given at a dosage of 5 mg/kg/d for 4 weeks. Compared with controls, BTX resulted in lower periosteal bone formation rate (BFR/BS,-79%, Pbone mineral density (aBMD, -13%, Pbone volume (BV/TV, -26%, Pbone strength (-12%, Pbone strength was found. In addition, GH partly prevented loss of muscle mass (+29% vs. BTX, P<0.001), and tended to prevent loss of muscle CSA (+11%, P=0.064). In conclusion, GH mitigates disuse-induced loss of periosteal BFR/BS at the mid-femur and rectus femoris muscle mass.

  12. 76 FR 62093 - Preventing Occupational Hearing Loss: Stakeholder Meeting

    Science.gov (United States)

    2011-10-06

    ... stakeholder meeting on preventing occupational hearing loss. Every year, between 20,000 and 25,000 workers suffer from preventable hearing loss due to high workplace noise levels. The purpose of this meeting is... nearly 125,000 workers have suffered significant, permanent hearing loss since 2004. Neither surgery nor...

  13. High dietary calcium intake does not counteract disuse-induced bone loss

    Science.gov (United States)

    Baecker, N.; Boese, A.; Smith, S. M.; Heer, M.

    Reduction of mechanical stress on bone inhibits osteoblast-mediated bone formation, increases osteoclast-mediated bone resorption, and leads to what has been called disuse osteoporosis. Prolonged therapeutic bed rest, immobilization and space flight are common causes of disuse osteoporosis. There are sufficient data supporting the use of calcium in combination with vitamin D in the prevention and treatment of postmenopausal osteoporosis. In our study we examined the potential of high dietary calcium intake as a nutrition therapy for disuse-induced bone loss during head-down bed rest in healthy young men. In 2 identical metabolic ward, head-down bed rest (HDBR) experiments (crossover design), we studied the effect of high dietary calcium intake (2000 mg/d) in comparison to the recommended calcium intake of 1000 mg/d on markers of bone turnover. Experiment A (EA) was a 6-day randomized, controlled HDBR study. Experiment B (EB) was a 14-day randomized, controlled HDBR study. In both experiments, the test subjects stayed under well-controlled environmental conditions in our metabolic ward. Subjects' diets in the relevant study phases (HDBR versus Ambulatory Control) of EA and EB were identical except for the calcium intake. The subjects obtained 2000 mg/d Calcium in EA and 2000 mg/d in EB. Blood was drawn at baseline, before entering the relevant intervention period, on day 5 in study EA, and on days 6, 11 and 14 in study EB. Serum calcium, bone formation markers - Procollagen-I-C-Propeptide (PICP) and bone alkaline phosphatase (bAP) were analyzed in serum. 24h-urine was collected throughout the studies for determination of the excretion of calcium (UCaV) and a bone resorption marker, C-terminal telopeptide of collagen type I (UCTX). In both studies, serum calcium levels were unchanged. PICP tended to decrease in EA (p=0.08). In EB PICP decreased significantly over time (p=0.003) in both the control and HDBR periods, and tended to further decrease in the HDBR period (p

  14. Sheep model for osteoporosis: The effects of peripheral hormone therapy on centrally induced systemic bone loss in an osteoporotic sheep model.

    Science.gov (United States)

    Oheim, Ralf; Simon, Maciej J K; Steiner, Malte; Vettorazzi, Eik; Barvencik, Florian; Ignatius, Anita; Amling, Michael; Clarke, Iain J; Pogoda, Pia; Beil, F Timo

    2017-04-01

    Hypothalamic-pituitary disconnection (HPD) leads to low bone turnover followed by bone loss and reduced biomechanical properties in sheep. To investigate the role of peripheral hormones in this centrally induced systemic bone loss model, we planned a hormone replacement experiment. Therefore, estrogen (OHE), thyroxin (OHT) or a combination of both (OHTE) was substituted in ovariectomized HPD sheep, as both hormones are decreased in HPD sheep and are known to have a significant but yet not fully understood impact on bone metabolism. Bone turnover and structural parameters were analyzed in comparison to different control groups - untreated sheep (C), ovariectomized (O) and ovariectomized+HPD sheep (OH). We performed histomorphometric and HR-pQCT analyses nine months after the HPD procedure, as well as biomechanical testing of all ewes studied. In HPD sheep (OH) the low bone turnover led to a significant bone loss. Treatment with thyroxin alone (OHT) mainly increased bone resorption, leading to a further reduction in bone volume. In contrast, the treatment with estrogen alone (OHE) and the combined treatment with estrogen and thyroxin (OHTE) prevented HPD-induced bone loss completely. In conclusion, peripheral hormone substitution was able to prevent HPD-induced low-turnover osteoporosis in sheep. But only the treatment with estrogen alone or in combination with thyroxin was able to completely preserve bone mass and structure. These findings demonstrate the importance of peripheral hormones for a balanced bone remodeling and a physiological bone turnover. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Marginal bone loss in implants placed in grafted maxillary sinus.

    Science.gov (United States)

    Galindo-Moreno, Pablo; Fernández-Jiménez, Andrés; O'Valle, Francisco; Silvestre, Francisco J; Sánchez-Fernández, Elena; Monje, Alberto; Catena, Andrés

    2015-04-01

    The purpose of this study is to evaluate the vertical and horizontal graft bone resorption (GR) in grafted maxillary sinuses and the marginal bone loss (MBL) around implants placed in the sinuses with different prosthetic connections and to determine the effect of other clinical factors on these tissue responses at 6 and 18 months postloading. A total of 254 implants were placed in 150 grafted maxillary sinuses of 101 patients (51.5% female) with mean age of 52.2 years (range, 32-82 years). GR and MBL measurements were made in implants placed with two different prosthetic connections (internal and external) at 6 and 18 months postloading. The complex samples general linear model was used to analyze the influence of patient age, gender, smoking habit, history of periodontal disease, implantation timing (simultaneous vs deferred), and prosthetic abutment length on radiographic GR and MBL values. At 18 months postloading, the MBL ranged from 0 mm to 5.89 mm; less than 1 mm was lost around 49.0% (mesial) and 44.3% (distal) of the implants, while no bone was lost around 32.9% (mesial) and 26.7% (distal). The GR was significantly affected by smoking, remnant alveolar bone height, graft length, graft height, gender, and age, and it significantly decreased over time. The MBL was influenced by the type of connection, implantation timing, and prosthetic abutment length. The MBL was greater with longer postloading interval and higher patient age and in smokers. Resorption of grafts that combine autogenous cortical bone with anorganic bovine bone is dependent on the anatomic features of the sinus and is not affected by the time elapsed after the first 6 months. The MBL in implants placed in these grafted areas is time dependent and mainly related to potentially modifiable clinical decisions and patient habits. © 2013 Wiley Periodicals, Inc.

  16. Artificial Gravity as a Bone Loss Countermeasure in Simulated Weightlessness

    Science.gov (United States)

    Smith, S. M.; Zwart, S. R.; Crawford, G. E.; Gillman, P. L.; LeBlanc, A.; Shackelford, L. C.; Heer, M. A.

    2007-01-01

    The impact of microgravity on the human body is a significant concern for space travelers. We report here initial results from a pilot study designed to explore the utility of artificial gravity (AG) as a countermeasure to the effects of microgravity, specifically to bone loss. After an initial phase of adaptation and testing, 15 male subjects underwent 21 days of 6 head-down bed rest to simulate the deconditioning associated with space flight. Eight of the subjects underwent 1 h of centrifugation (AG, 1 gz at the heart, 2.5 gz at the feet) each day for 21 days, while 7 of the subjects served as untreated controls (CN). Blood and urine were collected before, during, and after bed rest for bone marker determinations. At this point, preliminary data are available on the first 8 subjects (6 AG, and 2 CN). Comparing the last week of bed rest to before bed rest, urinary excretion of the bone resorption marker n-telopeptide increased 95 plus or minus 59% (mean plus or minus SD) in CN but only 32 plus or minus 26% in the AG group. Similar results were found for another resorption marker, helical peptide (increased 57 plus or minus 0% and 35 plus or minus 13% in CN and AG respectively). Bone-specific alkaline phosphatase, a bone formation marker, did not change during bed rest. At this point, sample analyses are continuing, including calcium tracer kinetic studies. These initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest.

  17. Aerobic Exercise and Whole-Body Vibration in Offsetting Bone Loss in Older Adults

    Directory of Open Access Journals (Sweden)

    Pei-Yang Liu

    2011-01-01

    Full Text Available Osteoporosis and its associated fractures are common complications of aging and most strategies to prevent and/or treat bone loss focused on antiresorptive medications. However, aerobic exercise (AEX and/or whole-body vibration (WBV might have beneficial effect on bone mass and provide an alternative approach to increase or maintain bone mineral density (BMD and reduce the risk of fractures. The purpose of this paper was to investigate the potential benefits of AEX and WBV on BMD in older population and discuss the possible mechanisms of action. Several online databases were utilized and based on the available literature the consensus is that both AEX and WBV may increase spine and femoral BMD in older adults. Therefore, AEX and WBV could serve as nonpharmacological and complementary approaches to increasing/maintaining BMD. However, it is uncertain if noted effects could be permanent and further studies are needed to investigate sustainability of either type of the exercise.

  18. Comparison of Bone Loss around Bone Platform Shift and Non-Bone Platform Shift Implants After 12 Months

    Directory of Open Access Journals (Sweden)

    AmirReza Rokn

    2015-10-01

    Full Text Available Objectives: The aim of the present randomized clinical trial was to evaluate marginal bone loss around two types of implants modified at the neck area: Nobel Active and Nobel Replace Groovy, both manufactured by Nobel Biocare.Materials and Methods: A total of 25 Nobel Active and 21 Nobel Replace Groovy implants were included in the present study. The implants were placed based on the relevant protocol and patient inclusion and exclusion criteria. The amount of bone loss around implants was compared at 6 and 12-month intervals using digital periapical radiographs.Results: The mean bone loss values in the Nobel Active and Nobel Replace Groovy groups were 0.682 mm and 0.645 mm, respectively, with no statistically significant difference based on the results of independent t-test (P=0.802.Conclusion: Use of both implant types yielded favorable results, with high durability.The two implant types exhibited no superiority over each other in terms of bone loss.

  19. Loss of Bone and Wnt10b Expression in Male Type 1 Diabetic Mice Is Blocked by the Probiotic Lactobacillus reuteri

    Science.gov (United States)

    Zhang, Jing; Motyl, Katherine J.; Irwin, Regina; MacDougald, Ormond A.; Britton, Robert A.

    2015-01-01

    Type 1 diabetes (T1D)–induced osteoporosis is characterized by a predominant suppression of osteoblast number and activity, as well as increased bone marrow adiposity but no change in osteoclast activity. The fundamental mechanisms and alternative anabolic treatments (with few side effects) for T1D bone loss remain undetermined. Recent studies by our laboratory and others indicate that probiotics can benefit bone health. Here, we demonstrate that Lactobacillus reuteri, a probiotic with anti-inflammatory and bone health properties, prevents T1D-induced bone loss and marrow adiposity in mice. We further found that L. reuteri treatment prevented the suppression of Wnt10b in T1D bone. Consistent with a role for attenuated bone Wnt10b expression in T1D osteoporosis, we observed that bone-specific Wnt10b transgenic mice are protected from T1D bone loss. To examine the mechanisms of this protection, we focused on TNF-α, a cytokine up-regulated in T1D that causes suppression of osteoblast Wnt10b expression in vitro. Addition of L. reuteri prevented TNF-α–mediated suppression of Wnt10b and osteoblast maturation markers. Taken together, our findings reveal a mechanism by which T1D causes bone loss and open new avenues for use of probiotics to benefit the bone. PMID:26135835

  20. Interventions to prevent occupational noise induced hearing loss

    NARCIS (Netherlands)

    Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wout; Sorgdrager, Bas

    2009-01-01

    BACKGROUND: Millions of workers worldwide are exposed to noise levels that increase their risk of hearing impairment. Little is known about the effectiveness of hearing loss prevention interventions. OBJECTIVES: To assess the effectiveness of non-pharmaceutical interventions for preventing

  1. Interventions to prevent occupational noise-induced hearing loss

    NARCIS (Netherlands)

    Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wouter A.; Mischke, Christina

    2012-01-01

    Background Millions of workers worldwide are exposed to noise levels that increase their risk of hearing impairment. Little is known about the effectiveness of hearing loss prevention interventions. Objectives To assess the effectiveness of non-pharmaceutical interventions for preventing

  2. CD38 is associated with premenopausal and postmenopausal bone mineral density and postmenopausal bone loss.

    LENUS (Irish Health Repository)

    Drummond, Frances J

    2012-02-03

    One goal of osteoporosis research is to identify the genes and environmental factors that contribute to low bone mineral density (BMD) and fracture. Linkage analyses have identified quantitative trait loci (QTLs), however, the genes contributing to low BMD are largely unknown. We examined the potential association of an intronic polymorphism in CD38 with BMD and postmenopausal bone loss. CD38 resides in 4p15, where a QTL for BMD has been described. CD38-\\/- mice display an osteoporotic phenotype at 3 months, with normalization of BMD by 5 months. The CD38 polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 457 postmenopausal and 173 premenopausal Caucasian women whose spine and hip BMD was measured by dual energy X-ray absorptiometry (DXA). Influence of the CD38 polymorphism on bone loss was analyzed in 273 postmenopausal women over a follow-up of 2.94 +\\/- 1.50 years. The CD38-PvuII polymorphism was significantly associated with premenopausal and postmenopausal (P = 0.001) lumbar spine BMD. Women homozygous for the G allele had >14% lower spinal BMD than women with GC\\/CC genotypes. An allele dose effect was observed at the spine in premenopausal (P = 0.002) and postmenopausal (P < 0.001) cohorts. The CD38-PvuII polymorphism was significantly associated with femoral neck BMD in pre- and postmenopausal women (P = 0.002 and P = 0.011, respectively). However, significance was lost following adjustment of hip BMD for covariates in the postmenopausal cohort (P = 0.081). The CD38-PvuII polymorphism was weakly associated with bone loss at the spine (P = 0.024), in postmenopausal women not taking hormone replacement therapy. We suggest that the CD38-PvuII polymorphism may influence the attainment and maintenance of peak BMD and postmenopausal bone loss.

  3. Effects of Resveratrol Supplementation on  Methotrexate Chemotherapy-Induced Bone Loss.

    Science.gov (United States)

    Lee, Alice M C; Shandala, Tetyana; Soo, Pei Pei; Su, Yu-Wen; King, Tristan J; Chen, Ke-Ming; Howe, Peter R; Xian, Cory J

    2017-03-09

    Intensive cancer chemotherapy is known to cause bone defects, which currently lack treatments. This study investigated the effects of polyphenol resveratrol (RES) in preventing bone defects in rats caused by methotrexate (MTX), a commonly used antimetabolite in childhood oncology. Young rats received five daily MTX injections at 0.75 mg/kg/day. RES was orally gavaged daily for seven days prior to, and during, five-day MTX administration. MTX reduced growth plate thickness, primary spongiosa height, trabecular bone volume, increased marrow adipocyte density, and increased mRNA expression of the osteogenic, adipogenic, and osteoclastogenic factors in the tibial bone. RES at 10 mg/kg was found not to affect bone health in normal rats, but to aggravate the bone damage in MTX-treated rats. However, RES supplementation at 1 mg/kg preserved the growth plate, primary spongiosa, bone volume, and lowered the adipocyte density. It maintained expression of genes involved in osteogenesis and decreased expression of adipogenic and osteoclastogenic factors. RES suppressed osteoclast formation ex vivo of bone marrow cells from the treated rats. These data suggest that MTX can enhance osteoclast and adipocyte formation and cause bone loss, and that RES supplementation at 1 mg/kg may potentially prevent these bone defects.

  4. Marginal bone loss around implants placed in maxillary native bone or grafted sinuses: a retrospective cohort study.

    Science.gov (United States)

    Galindo-Moreno, P; Fernández-Jiménez, A; Avila-Ortiz, G; Silvestre, F J; Hernández-Cortés, P; Wang, H L

    2014-03-01

    To assess differences in marginal bone loss around implants placed in maxillary pristine bone and implants placed following maxillary sinus augmentation over a period of 3 years after functional loading. Two cohorts of subjects (Group 1: Subjects who received sinus augmentation with simultaneous implant placement; Group 2: Subjects who underwent conventional implant placement in posterior maxillary pristine bone) were included in this retrospective study. Radiographic marginal bone loss was measured around one implant per patient on digitized panoramic radiographs that were obtained at the time of prosthesis delivery (baseline) and 12, 24, and 36 months later. The influence of age, gender, smoking habits, history of periodontal disease, and type of prosthetic connection (internal or external) on marginal bone loss was analyzed in function of the type of osseous support (previously grafted or pristine). A total of 105 subjects were included in this study. Cumulative radiographic marginal bone loss ranged from 0 mm to 3.9 mm after 36 months of functional loading. There were statistically significant differences in marginal bone loss between implants placed in grafted and pristine bone at the 12-month assessment, but not in the subsequent progression rate. External prosthetic connection, smoking, and history of periodontitis negatively influenced peri-implant bone maintenance, regardless of the type of osseous substrate. Implants placed in sites that received maxillary sinus augmentation exhibited more marginal bone loss than implants placed in pristine bone, although marginal bone loss mainly occurred during the first 12 months after functional loading. Implants with external implant connection were strongly associated with increased marginal bone loss overtime. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  5. Bone turnover markers in peripheral blood and marrow plasma reflect trabecular bone loss but not endocortical expansion in aging mice.

    Science.gov (United States)

    Shahnazari, Mohammad; Dwyer, Denise; Chu, Vivian; Asuncion, Frank; Stolina, Marina; Ominsky, Michael; Kostenuik, Paul; Halloran, Bernard

    2012-03-01

    We examined age-related changes in biochemical markers and regulators of osteoblast and osteoclast activity in C57BL/6 mice to assess their utility in explaining age-related changes in bone. Several recently discovered regulators of osteoclasts and osteoblasts were also measured to assess concordance between their systemic levels versus their levels in marrow plasma, to which bone cells are directly exposed. MicroCT of 6-, 12-, and 24-month-old mice indicated an early age-related loss of trabecular bone volume and surface, followed by endocortical bone loss and periosteal expansion. Trabecular bone loss temporally correlated with reductions in biomarkers of bone formation and resorption in both peripheral blood and bone marrow. Endocortical bone loss and periosteal bone gain were not reflected in these protein biomarkers, but were well correlated with increased expression of osteocalcin, rank, tracp5b, and cathepsinK in RNA extracted from cortical bone. While age-related changes in bone turnover markers remained concordant in blood versus marrow, aging led to divergent changes in blood versus marrow for the bone cell regulators RANKL, OPG, sclerostin, DKK1, and serotonin. Bone expression of runx2 and osterix increased progressively with aging and was associated with an increase in the number of osteoprogenitors and osteoclast precursors. In summary, levels of biochemical markers of bone turnover in blood and bone marrow plasma were predictive of an age-related loss of trabecular surfaces in adult C57BL/6 mice, but did not predict gains in cortical surfaces resulting from cortical expansion. Unlike these turnover markers, a panel of bone cell regulatory proteins exhibited divergent age-related changes in marrow versus peripheral blood, suggesting that their circulating levels may not reflect local levels to which osteoclasts and osteoblasts are directly exposed. Published by Elsevier Inc.

  6. Osteoprotegerin is an effective countermeasure for spaceflight-induced bone loss in mice.

    Science.gov (United States)

    Lloyd, Shane A; Morony, Sean E; Ferguson, Virginia L; Simske, Steven J; Stodieck, Louis S; Warmington, Kelly S; Livingston, Eric W; Lacey, David L; Kostenuik, Paul J; Bateman, Ted A

    2015-12-01

    Bone loss associated with microgravity exposure poses a significant barrier to long-duration spaceflight. Osteoprotegerin-Fc (OPG-Fc) is a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor that causes sustained inhibition of bone resorption after a single subcutaneous injection. We tested the ability of OPG-Fc to preserve bone mass during 12 days of spaceflight (SF). 64-day-old female C57BL/6J mice (n=12/group) were injected subcutaneously with OPG-Fc (20mg/kg) or an inert vehicle (VEH), 24h prior to launch. Ground control (GC) mice (VEH or OPG-Fc) were maintained under environmental conditions that mimicked those in the space shuttle middeck. Age-matched baseline (BL) controls were sacrificed at launch. GC/VEH, but not SF/VEH mice, gained tibia BMD and trabecular volume fraction (BV/TV) during the mission (P<0.05 vs. BL). SF/VEH mice had lower BV/TV vs. GC/VEH mice, while SF/OPG-Fc mice had greater BV/TV than SF/VEH or GC/VEH. SF reduced femur elastic and maximum strength in VEH mice, with OPG-Fc increasing elastic strength in SF mice. Serum TRAP5b was elevated in SF/VEH mice vs. GC/VEH mice. Conversely, SF/OPG-Fc mice had lower TRAP5b levels, suggesting that OPG-Fc preserved bone during spaceflight via inhibition of osteoclast-mediated bone resorption. Decreased bone formation also contributed to the observed osteopenia, based on the reduced femur periosteal bone formation rate and serum osteocalcin level. Overall, these observations suggest that the beneficial effects of OPG-Fc during SF are primarily due to dramatic and sustained suppression of bone resorption. In growing mice, this effect appears to compensate for the SF-related inhibition of bone formation, while preventing any SF-related increase in bone resorption. We have demonstrated that the young mouse is an appropriate new model for SF-induced osteopenia, and that a single pre-flight treatment with OPG-Fc can effectively prevent the deleterious effects of SF on mouse bone. Copyright

  7. Annual bone loss and success rates of dental implants based on radiographic measurements

    NARCIS (Netherlands)

    Geraets, W.; Zhang, L.; Liu, Y.; Wismeijer, D.

    2014-01-01

    Objectives: Bone loss around dental implants is generally measured by monitoring changes in marginal bone level using radiographs. After the first year of implantation, an implant should have <0.2 mm annual loss of marginal bone level to satisfy the criteria of success. However, the process of

  8. Olives and Bone: A Green Osteoporosis Prevention Option

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    2016-07-01

    Full Text Available Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis. Consumption of olives, olive oil and olive polyphenols has been shown to improve bone health. This review aims to summarize the current evidence from cellular, animal and human studies on the skeletal protective effects of olives, olive oil and olive polyphenols. Animal studies showed that supplementation of olives, olive oil or olive polyphenols could improve skeletal health assessed via bone mineral density, bone biomechanical strength and bone turnover markers in ovariectomized rats, especially those with inflammation. The beneficial effects of olive oil and olive polyphenols could be attributed to their ability to reduce oxidative stress and inflammation. However, variations in the bone protective, antioxidant and anti-inflammatory effects between studies were noted. Cellular studies demonstrated that olive polyphenols enhanced proliferation of pre-osteoblasts, differentiation of osteoblasts and decreased the formation of osteoclast-like cells. However, the exact molecular pathways for its bone health promoting effects are yet to be clearly elucidated. Human studies revealed that daily consumption of olive oil could prevent the decline in bone mineral density and improve bone turnover markers. As a conclusion, olives, olive oil and its polyphenols are potential dietary interventions to prevent osteoporosis among the elderly.

  9. Organizing knowledge for tutoring fire loss prevention

    Science.gov (United States)

    Daniel L. Schmoldt

    1989-01-01

    The San Bernardino National Forest in southern California has recently developed a systematic approach to wildfire prevention planning. However, a comprehensive document or other mechanism for teaching this process to other prevention personnel does not exist. An intelligent tutorial expert system is being constructed to provide a means for learning the process and to...

  10. Does vitamin D deficiency contribute to post-burn bone loss? [v1; ref status: indexed, http://f1000r.es/QLDkCs

    Directory of Open Access Journals (Sweden)

    Gordon L Klein

    2012-11-01

    Full Text Available Burn injury results in the acute loss of bone as well as the development of progressive vitamin D deficiency. Bone loss occurs acutely due to resorption, which is then followed by apoptosis of osteoblasts preventing repair of the bone loss. The acute resorption is due to a combination of the inflammatory response and the stress response to the burn injury. The resultant production of inflammatory cytokines and endogenous glucocorticoids initially stimulate the osteoblasts to produce RANK ligand, which stimulates marrow stem cell differentiation into osteoclasts. As the stress response persists for approximately one year post-burn the glucocorticoids produced by the body will cause osteoblast apoptosis and adynamic bone, impairing the ability of bone to recover its resorptive losses. The vitamin D deficiency is due to the failure to supplement the diet of burn patients with vitamin D on discharge from hospital and to failure of the skin to make normal quantities of vitamin D on sunlight exposure. Because the bone resorption can be prevented by the acute administration of bisphosphonates it is unlikely that vitamin D deficiency is responsible for the early-onset bone loss following burns. However, because a deficit in trabecular bone remains for at least two years post-burn, it is possible that vitamin D deficiency prevents the recovery of trabecular bone density over the long term.

  11. The prevention of losses in cured fish

    National Research Council Canada - National Science Library

    1981-01-01

    The paper reviews problems of the post-harvest losses in cured fish. The importance of this commodity in the tropics and existing methods of its handling, processing, storage and distribution are discussed...

  12. Ethanol Extract of Atractylodes macrocephala Protects Bone Loss by Inhibiting Osteoclast Differentiation

    Directory of Open Access Journals (Sweden)

    Youn-Hwan Hwang

    2013-06-01

    Full Text Available The rhizome of Atractylodes macrocephala has been used mainly in Traditional Chinese Medicine for invigorating the functions of the stomach and spleen. In the present study, we investigated the inhibitory effect of the 70% ethanol extract of the rhizome of Atractylodes macrocephala (AMEE on osteoclast differentiation. We found that AMEE inhibits osteoclast differentiation from its precursors induced by receptor activator of nuclear factor-κB ligand (RANKL, an essential cytokine required for osteoclast differentiation. AMEE attenuated RANKL-induced activation of NF-κB signaling pathway, subsequently inhibiting the induction of osteoclastogenic transcription factors, c-Fos and nuclear factor of activated T cells cytoplasmic 1. Consistent with the in vitro results, administration of AMEE protected RANKL-induced bone loss in mice. We also identified atractylenolide I and II as active constituents contributing to the anti-osteoclastogenic effect of AMEE. Taken together, our results demonstrate that AMEE has a protective effect on bone loss via inhibiting osteoclast differentiation and suggest that AMEE may be useful in preventing and treating various bone diseases associated with excessive bone resorption.

  13. Organizing knowledge for tutoring fire loss prevention

    Science.gov (United States)

    Schmoldt, Daniel L.

    1989-09-01

    The San Bernardino National Forest in southern California has recently developed a systematic approach to wildfire prevention planning. However, a comprehensive document or other mechanism for teaching this process to other prevention personnel does not exist. An intelligent tutorial expert system is being constructed to provide a means for learning the process and to assist in the creation of specific prevention plans. An intelligent tutoring system (ITS) contains two types of knowledge—domain and tutoring. The domain knowledge for wildfire prevention is structured around several foci: (1) individual concepts used in prevention planning; (2) explicitly specified interrelationships between concepts; (3) deductive methods that contain subjective judgment normally unavailable to less-experienced users; (4) analytical models of fire behavior used for identification of hazard areas; (5) how-to guidance needed for performance of planning tasks; and (6) expository information that provides a rationale for planning steps and ideas. Combining analytical, procedure, inferential, conceptual, and expositional knowledge into a tutoring environment provides the student and/or user with a multiple perspective of the subject matter. A concept network provides a unifying framework for structuring and utilizing these diverse forms of prevention planning knowledge. This network structure borrows from and combines semantic networks and frame-based knowledge representations. The flexibility of this organization facilitates an effective synthesis and organization of multiple knowledge forms.

  14. Candidate salivary biomarkers associated with alveolar bone loss: cross-sectional and in vitro studies

    OpenAIRE

    Ng, Patricia Yen Bee; Donley, Maureen; Hausmann, Ernest; Hutson, Alan D.; Rossomando, Edward F.; Scannapieco, Frank A.

    2007-01-01

    This cross-sectional study evaluated the association between radiographic evidence of alveolar bone loss and the concentration of host-derived bone resorptive factors (interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, prostaglandin-E2), and markers of bone turnover [pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), osteocalcin, osteonectin] in stimulated human whole saliva collected from 110 untreated dental patients. Alveolar bone loss scores for ...

  15. Exercise and pharmacological countermeasures for bone loss during long-duration space flight

    Science.gov (United States)

    Cavanagh, Peter R.; Licata, Angelo A.; Rice, Andrea J.

    2005-01-01

    Bone loss in the lower extremities and lumbar spine is an established consequence of long-duration human space flight. Astronauts typically lose as much bone mass in the proximal femur in 1 month as postmenopausal women on Earth lose in 1 year. Pharmacological interventions have not been routinely used in space, and countermeasure programs have depended solely upon exercise. However, it is clear that the osteogenic stimulus from exercise has been inadequate to maintain bone mass, due to insufficient load or duration. Attention has therefore been focused on several pharmacological interventions that have been successful in preventing or attenuating osteoporosis on Earth. Anti-resorptives are the class of drugs most commonly used to treat osteoporosis in postmenopausal women, notably alendronate sodium, risedronate sodium, zoledronic acid, and selective estrogen receptor modulators, such as raloxifene. There has also been considerable recent interest in anabolic agents such as parathyroid hormone (PTH) and teriparatide (rhPTH [1-34]). Vitamin D and calcium supplementation have also been used. Recent studies of kindreds with abnormally high bone mineral density have provided insight into the genetic regulation of bone mass. This has led to potential therapeutic interventions based on the LRP5, Wnt and BMP2 pathways. Another target is the RANK-L/osteoprotegerin signaling pathway, which influences bone turnover by regulating osteoclast formation and maturation. Trials using such therapies in space are being planned. Among the factors to be considered are dose-response relationships, bone quality, post-use recovery, and combination therapies--all of which may have unique characteristics when the drugs are used in space.

  16. Conductive hearing loss and bone conduction devices: restored binaural hearing?

    Science.gov (United States)

    Agterberg, Martijn J H; Hol, Myrthe K S; Cremers, Cor W R J; Mylanus, Emmanuel A M; van Opstal, John; Snik, Ad F M

    2011-01-01

    An important aspect of binaural hearing is the proper detection of interaural sound level differences and interaural timing differences. Assessments of binaural hearing were made in patients with acquired unilateral conductive hearing loss (UCHL, n = 11) or congenital UCHL (n = 10) after unilateral application of a bone conduction device (BCD), and in patients with bilateral conductive or mixed hearing loss after bilateral BCD application. Benefit (bilateral versus unilateral listening) was assessed by measuring directional hearing, compensation of the acoustic head shadow, binaural summation and binaural squelch. Measurements were performed after an acclimatization time of at least 10 weeks. Unilateral BCD application was beneficial, but there was less benefit in the patients with congenital UCHL as compared to patients with acquired UCHL. In adults with bilateral hearing loss, bilateral BCD application was clearly beneficial as compared to unilateral BCD application. Binaural summation was present, but binaural squelch could not be proven. To explain the poor results in the patients with congenital UCHL, two factors seemed to be important. First, a critical period in the development of binaural hearing might affect the binaural hearing abilities. Second, crossover stimulation, referring to additional stimulation of the cochlea contralateral to the BCD side, might deteriorate binaural hearing in patients with UCHL. Copyright © 2011 S. Karger AG, Basel.

  17. Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis.

    Science.gov (United States)

    Donahue, Seth W; Galley, Sarah A; Vaughan, Michael R; Patterson-Buckendahl, Patricia; Demers, Laurence M; Vance, Josef L; McGee, Meghan E

    2006-05-01

    Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears (Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured the serum concentrations of hormones and growth factors involved in bone metabolism and correlated them with the serum concentration of a bone formation marker (osteocalcin). Serum was obtained from black bears over a 7-month duration that included periods of activity and inactivity. Both resorption and formation markers increased during hibernation, suggesting high bone turnover occurred during inactivity. However, bone formation appeared to be balanced with bone resorption. The serum concentration of parathyroid hormone (PTH) was higher in the hibernation (P=0.35) and post-hibernation (P=0.006) seasons relative to pre-hibernation levels. Serum leptin was lower (Phibernation relative to pre-hibernation and hibernation periods. Insulin-like growth factor I (IGF-I) decreased (Phibernation relative to pre-hibernation and reached its highest value during remobilization. There was no difference (P=0.64) in 25-OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker) was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH vitamin D. Osteocalcin and PTH were positively correlated when samples from all seasons were pooled and when only hibernation samples were considered, raising the possibility that the anabolic actions of PTH help maintain bone formation to prevent disuse osteoporosis. Prostaglandin E(2) (PGE(2)) release from MC3T3 osteoblastic cells was significantly affected by treatment with bear serum from different seasons (i.e. hibernation versus active periods). The seasonal changes in PGE(2) release showed trends similar to the

  18. Vascularized fibular graft in infected tibial bone loss

    Directory of Open Access Journals (Sweden)

    C Cheriyan Kovoor

    2011-01-01

    Full Text Available Background : The treatment options of bone loss with infections include bone transport with external fixators, vascularized bone grafts, non-vascularized autogenous grafts and vascularized allografts. The research hypothesis was that the graft length and intact ipsilateral fibula influenced hypertrophy and stress fracture. We retrospectively studied the graft hypertrophy in 15 patients, in whom vascularized fibular graft was done for post-traumatic tibial defects with infection. Materials and Methods : 15 male patients with mean age 33.7 years (range 18 - 56 years of post traumatic tibial bone loss were analysed. The mean bony defect was 14.5 cm (range 6.5 - 20 cm. The mean length of the graft was 16.7 cm (range 11.5 - 21 cm. The osteoseptocutaneous flap (bone flap with attached overlying skin flap from the contralateral side was used in all patients except one. The graft was fixed to the recipient bone at both ends by one or two AO cortical screws, supplemented by a monolateral external fixator. A standard postoperative protocol was followed in all patients. The hypertrophy percentage of the vascularized fibular graft was calculated by a modification of the formula described by El-Gammal. The followup period averaged 46.5 months (range 24 - 164 months. The Pearson correlation coefficient (r was worked out, to find the relationship between graft length and hypertrophy. The t-test was performed to find out if there was any significant difference in the graft length of those who had a stress fracture and those who did not and to find out whether there was any significant difference in hypertrophy with and without ipsilateral fibula union. The Chi square test was performed to identify whether there was any association between the stress fracture and the fibula union. Given the small sample size we have not used any statistical analysis to determine the relation between the percentage of the graft hypertrophy and stress fracture. Results : Graft

  19. 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.

  20. Protease inhibitor-associated bone mineral density loss is related to hypothyroidism and related bone turnover acceleration.

    Science.gov (United States)

    Kinai, Ei; Gatanaga, Hiroyuki; Mizushima, Daisuke; Nishijima, Takeshi; Aoki, Takahiro; Genka, Ikumi; Teruya, Katsuji; Tsukada, Kunihisa; Kikuchi, Yoshimi; Oka, Shinichi

    2017-05-01

    Clinical and experiments evidence indicate that protease inhibitors (PI) can cause bone mineral density (BMD) loss. However, the mechanism of such loss remains obscure. This single-center, cross-sectional study included 184 HIV-infected patients treated with PI who underwent dual-energy X-ray absorptiometry scan. Serum phosphorus, percentage of tubular reabsorption of phosphate (%TRP), thyroid and parathyroid function (iPTH), vitamin D, osteocalcin (OC), urinary deoxypyridinoline (DPD), and urinary cross-linked N-telopeptide of type I collagen (u-NTx) were measured. The rate of hypothyroidism in PI-users [32/117 (27%)] was double that in non-PI users [8/67 (12%), p = 0.016] and was significantly associated with PI use in multivariate analysis [odds ratio (OR) 11.37, 95% confidence interval (CI) 1.358-95.17, p = 0.025]. Spine BMD was significantly lower in hypothyroid patients than euthyroid, for both total population (-1.37 vs. -1.00, p = 0.041) and PI users (-1.56 vs. -1.13, p = 0.029). Multivariate regression analysis identified inverse correlation between hypothyroidism and spine BMD [estimate -0.437, 95% CI -0.858 to -0.024, p = 0.042]. OC, DPD and u-NTx were significantly higher in PI users than in non-PI users (p = 0.01, 0.05, and 0.01, respectively). PI use is associated with hypothyroidism as well as bone turnover acceleration, which worsens PI-associated BMD loss. In PI-treated patients, thyroid function tests are warranted to prevent further progression of PI-associated BMD loss. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Single-nucleotide polymorphisms in the P2X7 receptor gene are associated with post-menopausal bone loss and vertebral fractures

    DEFF Research Database (Denmark)

    Rye Jørgensen, Niklas; Husted, Lise Bjerre; Skarratt, Kristen K

    2012-01-01

    to bone mass and fracture incidence in post-menopausal women. A total of 1694 women (aged 45-58) participating in the Danish Osteoporosis Prevention Study were genotyped for 12 functional P2X7 receptor variants. Bone mineral density was determined at baseline and after 10 years. In addition, vertebral...... had increased bone loss. In contrast, the Gln460Arg polymorphism was associated with protection against bone loss. The Ala348Thr polymorphism was associated with a lower vertebral fracture incidence 10 years after menopause. Finally, we developed a risk model, which integrated P2RX7 genotypes. Using...

  2. 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.

  3. Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

    Science.gov (United States)

    Foster, B.L.; Ao, M.; Willoughby, C.; Soenjaya, Y.; Holm, E.; Lukashova, L.; Tran, A. B.; Wimer, H.F.; Zerfas, P.M.; Nociti, F.H.; Kantovitz, K.R.; Quan, B.D.; Sone, E.D.; Goldberg, H.A.; Somerman, M.J.

    2015-01-01

    Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp−/− mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp−/− mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp−/− mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp−/− mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified

  4. Is there evidence that barrier membranes prevent bone resorption in autologous bone grafts during the healing period? A systematic review

    NARCIS (Netherlands)

    Gielkens, Pepijn F. M.; Bos, Ruud R. M.; Raghoebar, Gerry M.; Stegenga, Boudewijn

    2007-01-01

    Introduction: Autologous bone is considered the "reference standard" for bone-grafting procedures. A barrier membrane covering an autologous bone graft (guided bone regeneration [GBR]) is expected to prevent graft resorption. Good clinical results have been reported for GBR, although potential

  5. Dried Plum Protects From Radiation-Induced Bone Loss by Attenuating Pro-Osteoclastic and Oxidative Stress Responses

    Science.gov (United States)

    Globus, Ruth

    2015-01-01

    Future space explorations beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure plays a major role in progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Our long-term goals are to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures. We had previously reported that exposure to low or high-LET radiation correlates with an acute increase in the expression of pro-osteoclastic and oxidative stress genes in bone during the early response to radiation followed by pathological changes in skeletal structure. We then conducted systematic screening for potential countermeasures against bone loss where we tested the ability of various antioxidants to mitigate the radiation-induced increase in expression of these markers. For the screen, 16-week old C57Bl6J mice were treated with a dietary antioxidant cocktail, injectable DHLA or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs radiation and one day later, marrow cells were collected and the relevant genes analyzed for expression levels. Among the candidate countermeasures tested, DP was most effective in reducing the expression of genes associated with bone loss. Furthermore, analysis of skeletal structure by microcomputed tomography (microCT) revealed that DP also prevents the radiation-induced deterioration in skeletal microarchitecture as indicated by parameters such as percent bone volume (BVTV), trabecular spacing and trabecular number. We also found that DP has similar protective effects on skeletal structure in a follow-up study using 1 Gy of

  6. Marginal bone loss as success criterion in implant dentistry: beyond 2 mm.

    Science.gov (United States)

    Galindo-Moreno, Pablo; León-Cano, Ana; Ortega-Oller, Inmaculada; Monje, Alberto; O'Valle, Francisco; Catena, Andrés

    2015-04-01

    The aim of this study was to analyze marginal bone loss (MBL) rates around implants to establish the difference between physiological bone loss and bone loss due to peri-implantitis. Five hundred and eight implants were placed in the posterior maxilla in 208 patients. Data were gathered on age, gender, bone substratum (grafted or pristine), prosthetic connection, smoking and alcohol habits, and previous periodontitis. MBL was radiographically analyzed in three time frames (5 months post-surgery and at 6 and 18 months post-loading). Nonparametric receiver operating curve (ROC) analysis and mixed linear model analysis were used to determine whether implants could be classified as high or low bone loser type (BLT) and to establish the influence of this factor on MBL rates. Marginal bone loss rates were significantly affected by BLT, connection type, bone substratum, and smoking. Bone loss rates at 18 months were associated with initial bone loss rates: 96% of implants with an MBL of >2 mm at 18 months had lost 0.44 mm or more at 6 months post-loading. Implants with increased MBL rates at early stages (healing and immediate post-loading periods) are likely to reach MBL values that compromise their final outcome. Initial (healing, immediate post-loading) MBL rates around an implant of more than 0.44 mm/year are an indication of peri-implant bone loss progression. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Preventing Strength Loss of Unbleached Kraft Pulp

    Energy Technology Data Exchange (ETDEWEB)

    Martin Hubbe; Richard Venditti; John Heitmann

    2003-04-16

    Kraft pulp fibers lose inter-fiber bonding ability when they are dried during the manufacture of paper. Adverse environmental consequences of this loss include (a) limitations on the number of times that kraft fibers can be recycled, (b) reduced paper strength, sometimes making it necessary to use heavier paper or paperboard to meet product strength requirements, increasing the usage of raw materials, (c) decreased rates of paper production in cases where the fiber furnish has been over-refined in an attempt to regain inter-fiber bonding ability. The present study is the first of its type to focus on unbleached kraft fibers, which are a main ingredient of linerboard for corrugated containers. About 90 million tons of unbleached kraft fiber are used worldwide every year for this purpose.

  8. Diet, Weight Loss, and Cardiovascular Disease Prevention.

    Science.gov (United States)

    Bray, George A.; Ryan, Donna H.; Harsha, David W.

    2003-08-01

    Body weight, like cholesterol and blood pressure, are continuous variables. Overweight results when energy intake as food exceeds energy expenditure from exercise for a considerable period of time. When body weight becomes sufficiently high, it poses a risk to cardiovascular and metabolic health. The types of treatments considered by the physician and discussed with a patient should be based on this risk-benefit assessment. The body mass is the basic measurement for this assessment, and should be part of the "vital signs" when a patient is first evaluated by the medical staff. When the body mass index (BMI) is below 25 kg/m(2), there is little risk from the body weight, but because obesity is a "stigmatized" condition, many patients, particularly women, desire to lose weight even within the normal range. For this purpose, a high-quality diet like the Dietary Approaches to Stopping Hypertension (DASH) diet at a reduced-calorie intake would be our recommendation. When the BMI is above 25 kg/m(2), patients deserve dietary advice, but in addition to a reduced-calorie DASH-like diet, this is a place to consider using "portion-control" strategies, such as the nutrition labels that manufacturers provide on canned and frozen foods to guide patients in reducing calorie intake. In overweight individuals at high risk (ie, those with a BMI above 30 kg/m(2) or impaired glucose tolerance, hypertension, or the metabolic syndrome), the use of orlistat or sibutramine along with diet, exercise, lifestyle changes, and portion control should be considered. When the BMI is above 35 kg/m(2), bariatric surgery should also be discussed as an option for the "at-risk" individual. Evidence reviewed here shows that modest weight losses of 5% to 10% can reduce the risk of conversion from impaired glucose tolerance to diabetes and can maintain lower blood pressure over extended periods. All of the approaches described above can produce weight losses of this magnitude.

  9. Loss of PiT-2 results in abnormal bone development and decreased bone mineral density and length in mice.

    Science.gov (United States)

    Yamada, Shunsuke; Wallingford, Mary C; Borgeia, Suhaib; Cox, Timothy C; Giachelli, Cecilia M

    2018-01-01

    Normal bone mineralization requires phosphate oversaturation in bone matrix vesicles, as well as normal regulation of phosphate metabolism via the interplay among bone, intestine, and kidney. In turn, derangement of phosphate metabolism greatly affects bone function and structure. The type III sodium-dependent phosphate transporters, PiT-1 and PiT-2, are believed to be important in tissue phosphate metabolism and physiological bone formation, but their requirement and molecular roles in bone remain poorly investigated. In order to decipher the role of PiT-2 in bone, we examined normal bone development, growth, and mineralization in global PiT-2 homozygous knockout mice. PiT-2 deficiency resulted in reduced vertebral column, femur, and tibia length as well as mandibular dimensions. Micro-computed tomography analysis revealed that bone mineral density in the mandible, femur, and tibia were decreased, indicating that maintenance of bone function and structure is impaired in both craniofacial and long bones of PiT-2 deficient mice. Both cortical and trabecular thickness and mineral density were reduced in PiT-2 homozygous knockout mice compared with wild-type mice. These results suggest that PiT-2 is involved in normal bone development and growth and plays roles in cortical and trabecular bone metabolism feasibly by regulating local phosphate transport and mineralization processes in the bone. Further studies that evaluate bone cell-specific loss of PiT-2 are now warranted and may yield insight into complex mechanisms of bone development and growth, leading to identification of new therapeutic options for patients with bone diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. WIse-2005: Combined Aerobic and Resistive Exercise May Help Mitigate Bone Loss During 60-D Simulated Microgravity in Women

    Science.gov (United States)

    Smith, Scott M.; Zwart, S. R.; Heer, M. A.; Lee, S. M. C.; Macias, B. R.; Schneider, S. M.; Trappe, S. M.; Hargens, A. R.

    2006-01-01

    Exercise can attenuate bone loss associated with disuse during bed rest (BR), an analog of space flight. Previous studies have examined the efficacy of aerobic or resistive exercise countermeasures, but not in combination. We sought to determine the effect of a combined resistive and aerobic exercise regimen on bone metabolism during BR. After a 20-d ambulatory adaptation to confinement and diet, 16 women participated in a 60-d head-down-tilt BR. Control subjects (CN, n=8) performed no countermeasures. Exercise subjects, (EX, n=8) participated in exercise alternating daily between supine treadmill exercise within lower body negative pressure and resistive fly-wheel exercise (6-d wk(sup -1)). In the last week of BR, bone resorption was greater (p less than 79 plus or minus 44%, mean plus or minus SD) and EX groups (64 50%). N-telopeptide also increased (CN: 51 plus or minus 34%; EX: 43 plus or minus 56%). However, bone-specific alkaline phosphatase, a bone formation marker, tended to be higher in EX (26 plus or minus 18%) than in CN (8 plus or minus 33%) groups. The combination of resistive and aerobic exercise does not prevent bone resorption, but may promote formation, potentially mitigating the net bone loss associated with simulated microgravity. This study was supported by CNES, CSA, ESA, NASA, and NASA grant NNJ04HF71G to ARH. MEDES (French Institute for Space Medicine and Physiology) organized the study.

  11. Biglycan deficiency interferes with ovariectomy-induced bone loss

    DEFF Research Database (Denmark)

    Nielsen, Karina L; Allen, Matthew R; Bloomfield, Susan A

    2003-01-01

    were killed 4 weeks after surgery. Bone mass and bone turnover were analyzed by peripheral quantitative computed tomography (pQCT), biochemical markers, and histomorphometry. RESULTS AND CONCLUSIONS: In contrast to the male mice, there were only few effects of bgn deficiency on bone metabolism...... to biglycan deficiency. INTRODUCTION: Biglycan (bgn) is a small extracellular matrix proteoglycan enriched in skeletal tissues, and biglycan-deficient male mice have decreased trabecular bone mass and bone strength. The purpose of this study was to investigate the bone phenotype of the biglycan...

  12. Impact of annual bone loss and different bone quality on dental implant success - A finite element study.

    Science.gov (United States)

    Linetskiy, Igor; Demenko, Vladyslav; Linetska, Larysa; Yefremov, Oleg

    2017-12-01

    For dental implant success, experimentally established thresholds should limit bone stresses and strains. From these metrics, the ultimate functional load, which determines the implant load-carrying capacity, can be calculated. Obviously, its decrease due to bone loss shortens implant service life. A comparison of how bone loss affects the ultimate functional loads of various implants can provide the clinician with meaningful feedback concerning the suitability and longevity of implants. The aim of this study is to evaluate the lifetime of different dental implants placed in I-IV bone types on the basis of a comparison of their ultimate functional loads with consideration of the bone loss factor. Von Mises stress and first principal strain distributions in bone-implant interface were studied and ultimate functional loads were calculated. Models of I-IV bone types were designed. 3.3 × 8.0 mm (A), 4.1 × 12.0 mm (B) and 4.8 × 14.0 mm (C) implants were analyzed at 10 levels of bone loss. Ultimate functional loads, which generated the ultimate von Mises stress and first principal strain in bone, were computed. For the implants A, B, and C placed in type I bone, ultimate functional load values were above 120.92 N experimental functional load, which corresponded to 10+, 10+, and 10 + years of service with 0.2 mm annual bone loss. For type II bone, the lifetime was 4, 10+, and 10 + years. For type III bone, the lifetime was 4, 5, and 5 years. For type IV bone, first principal strains were initially deleterious for all implants. In oral implantology, bone loss is an essential factor for implant longevity prognosis. While evaluating implant load-carrying capacity, clinicians should take into account the factor of implant longevity decrease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The correlation between postmenopausal osteoporosis and inflammatory periodontitis regarding bone loss in experimental models.

    Science.gov (United States)

    Kobayashi, Megumi; Matsumoto, Chiho; Hirata, Michiko; Tominari, Tsukasa; Inada, Masaki; Miyaura, Chisato

    2012-01-01

    We have invented a mouse model of periodontitis associated with alveolar bone loss induced by lipopolysaccharide. Ovariectomized (OVX) animals are widely used as a model for osteoporosis due to estrogen deficiency. To define the relationship between periodontitis and osteoporosis, we examined the influence of estrogen deficiency on the mouse alveolar bone mass. In OVX mice, bone loss was detected not only in the femur, but also in the alveolar bone, indicating that estrogen deficiency could induce resorption in alveolar bone. In experiments using a combination of osteoporosis and periodontitis models, OVX significantly enhanced the alveolar bone loss in the model of periodontitis. Therefore, postmenopausal osteoporosis may enhance the risk of periodontitis associated with inflammatory alveolar bone resorption.

  14. Alcohol-induced bone loss is blocked in p47phox -/- mice lacking functional nadph oxidases

    Science.gov (United States)

    Chronic ethanol (EtOH) consumption produces bone loss. Previous data suggest a role for NADPH oxidase enzymes (Nox) since the pan-Nox inhibitor diphenylene iodonium (DPI) blocks EtOH-induced bone loss in rats. The current study utilized mice in which Nox enzymes 1,2,3 and 5 are inactivated as a resu...

  15. Pattern of bone loss in dry Mandibles of individuals who died before ...

    African Journals Online (AJOL)

    Pattern of bone loss in dry Mandibles of individuals who died before 1957. ... The total mean bone loss for all teeth was 2.51 (SD 1.15) with a range of 0.85-5.80. ... Thus susceptibility to periodontal disease is evident in a small proportion of individuals even in populations not exposed to modern diet and formal dental ...

  16. Knowledge about osteoporosis prevention among women screened by bone densitometry

    Directory of Open Access Journals (Sweden)

    Mariola Janiszewska

    2016-07-01

    Full Text Available Introduction : Osteoporosis is an illness characterized by the handicapped endurance of the bones, causing an increased risk of fracture. Aim of the study was to establish the level of knowledge about osteoporosis prevention among women screened by bone densitometry and to answer the question whether the level of knowledge is dependent on socio-demographic factors. Material and methods: The research was realized by means of a survey method, a poll technique in 2014. The study involved 292 women aged 51-83. The examined women were patients undergoing bone densitometry in the healthcare centres in Lublin. The osteoporosis knowledge test (OKT, revised 2011 by Phyllis Gendler was used as a research tool. Gathered material was subject to descriptive and statistical analysis. Tukey’s test, t-Student test and variance analysis (ANOVA were all applied. A statistical significance level was set at  = 0.05. Results and conclusions : Respondents presented the basic exercise knowledge (M = 9.97 and low knowledge concerning risk factors, screening and treatment of osteoporosis (M = 7.87. The calcium knowledge remained on an average level (M = 14.03. Better educated women, city inhabitants as well as women having very good or good social and welfare conditions showed a significantly higher level of knowledge about osteoporosis prevention. Even women undergoing bone densitometry examination present insufficient knowledge about osteoporosis prevention.

  17. Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model.

    Science.gov (United States)

    Courbon, Guillaume; Cleret, Damien; Linossier, Marie-Thérèse; Vico, Laurence; Marotte, Hubert

    2017-06-01

    Synovitis is usually observed before loss of articular function in rheumatoid arthritis (RA). In addition to the synovium and according to the "Inside-Outside" theory, bone compartment is also involved in RA pathogenesis. Then, we investigated time dependent articular bone loss and prediction of early bone loss to late arthritis severity on the rat adjuvant-induced arthritis (AIA) model. Lewis female rats were longitudinally monitored from arthritis induction (day 0), with early (day 10) and late (day 17) steps. Trabecular and cortical microarchitecture parameters of four ankle bones were assessed by microcomputed tomography. Gene expression was determined at sacrifice. Arthritis occurred at day 10 in AIA rats. At this time, bone erosions were detected on four ankle bones, with cortical porosity increase (+67%) and trabecular alterations including bone volume fraction (BV/TV: -13%), and trabecular thickness decrease. Navicular bone assessment was the most reproducible and sensitive. Furthermore, strong correlations were observed between bone alterations at day 10 and arthritis severity or bone loss at day 17, including predictability of day 10 BV/TV to day 17 articular index (R 2  = 0.76). Finally, gene expression at day 17 confirmed massive osteoclast activation and interestingly provided insights on strong activation of bone formation inhibitor markers at the joint level. In rat AIA, bone loss was already observed at synovitis onset and was predicted late arthritis severity. Our results reinforced the key role of subchondral bone in arthritis pathogenesis, in favour to the "Inside-Outside" theory. Mechanisms of bone loss in rat AIA involved resorption activation and formation inhibition changes. J. Cell. Physiol. 232: 1318-1325, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Age- and menopause-related bone loss compromise cortical and trabecular microstructure.

    Science.gov (United States)

    Seeman, Ego

    2013-10-01

    All factors influencing the material composition and structure of bone do so through the final common cellular pathways of modeling and remodeling. During growth, modeling, the formation of new bone in different locations without prior bone resorption, deposits matrix upon the periosteum, enlarging the cross-sectional area of bone. Concurrently, endocortical resorption excavates the medullary canal while remodeling, the resorption and deposition of bone in the same location, assembles cortical osteons, each with their central Haversian canal. The Haversian canals and the connecting Volkmann canals form an intracortical canal network that occupies 30% of the total cortical volume. The remaining 70% is mineralized bone matrix volume. Around midlife, in women, remodeling balance becomes negative; less bone is deposited than it is resorbed by each bone's basic multicellular units (BMUs), and remodeling rate increases; there are more BMUs removing bone upon its intracortical, endocortical, and trabecular surfaces. Canals enlarge and coalesce creating giant pores. Remodeling upon trabeculae removes them, whereas intracortical and endocortical remodeling cavitates and fragments the cortex. Bone loss becomes almost entirely cortical as trabeculae disappear. Remodeling removes more bone from a diminishing total mineralized bone matrix volume so that by old age, total mineralized bone matrix volume is halved; 70% of all bone loss is cortical because 80% of the skeleton is cortical; 30% of the bone loss arises from the 20% of the skeleton that is trabecular. Of all fractures occurring, 80% are nonvertebral and 20% are vertebral. The notion of osteoporosis as a disease of trabecular bone loss and vertebral fractures needs to be revised.

  19. The regulation of iron metabolism by hepcidin contributes to unloading-induced bone loss.

    Science.gov (United States)

    Xu, Zi; Sun, Weijia; Li, Yuheng; Ling, Shukuan; Zhao, Chenyang; Zhong, Guohui; Zhao, Dingsheng; Song, Jinping; Song, Hailin; Li, Jinqiao; You, Linhao; Nie, Guangjun; Chang, Yanzhong; Li, Yingxian

    2017-01-01

    Iron overload inhibits osteoblast function and promotes osteoclastogenesis. Hepcidin plays an important role in this process. The changes in iron content and the regulation of hepcidin under unloading-induced bone loss remain unknown. A hindlimb suspension model was adopted to simulate unloading-induced bone loss in mice. The results showed that iron deposition in both liver and bone was markedly increased in hindlimb unloaded mice, and was accompanied by the upregulation of osteoclast activity and downregulation of osteoblast activity. The iron chelator deferoxamine mesylate (DFO) reduced the iron content in bone and alleviated unloading-induced bone loss. The increased iron content in bone was mainly a result of the upregulation of transferrin receptor 1 (TfR1) and divalent metal transporter 1 with iron response element (DMT1+IRE), rather than changes in the iron transporter ferroportin 1 (FPN1). The hepcidin level in the liver was significantly higher, while the FPN1 level in the duodenum was substantially reduced. However, there were no changes in the FPN1 level in bone tissue. During hindlimb unloading, downregulation of hepcidin by siRNA increased iron uptake in bone and liver, which aggravated unloading-induced bone loss. In summary, these data show that unloading-induced bone loss was orchestrated by iron overload and coupled with the regulation of hepcidin by the liver. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Establishment of age- and sex-adjusted reference data for hand bone mass and investigation of hand bone loss in patients with rheumatoid arthritis treated in clinical practice

    DEFF Research Database (Denmark)

    Ørnbjerg, Lykke Midtbøll; Østergaard, Mikkel; Jensen, Trine

    2016-01-01

    BACKGROUND: Rheumatoid arthritis is characterised by progressive joint destruction and loss of periarticular bone mass. Hand bone loss (HBL) has therefore been proposed as an outcome measure for treatment efficacy. A definition of increased HBL adjusted for age- and sex-related bone loss is lacking...

  1. Mandibular Symphyseal/Parasymphyseal Fracture with Incisor Tooth Loss: Preventing Lower Arch Constriction.

    Science.gov (United States)

    Rahpeyma, Amin; Khajehahmadi, Saeedeh; Abdollahpour, Somayeh

    2016-03-01

    Mandibular fractures are the second most common fractures of the face after the nasal bone. Mandibular symphyseal/parasymphyseal fracture comprises 15.6 to 29.3% of mandibular fractures. Tooth loss in the fracture line is a known phenomenon, but space loss has not been evaluated comprehensively in the literature. In a retrospective study, patients with mandibular symphyseal/parasymphyseal fractures, who had been treated from 2012 to 2013 in Mashhad University, Iran, Emdadi Hospital, were recalled. Patients with mandibular incisor tooth/teeth loss were included in the study. Space loss, the technique used to replace the lost tooth/teeth, upper and lower dental midline relationship, combination fracture or fractures in other facial skeleton, and type of treatment were evaluated. Of 98 patients with mandibular symphyseal/parasymphyseal fractures, 22.5% had incisor tooth/teeth loss. In this group, 73% had space loss. Only four patients had replaced the lost tooth/teeth. Dental midlines did not match each other in patients whose feature was evaluated. Open reduction and internal fixation with miniplates were used in symphyseal/parasymphyseal fractures except one. Space loss after mandibular symphyseal/parasymphyseal fracture with incisor tooth loss is a common error. The most important factor to prevent complications related to space loss following mandibular symphyseal/parasymphyseal fracture accompanying incisor tooth loss is space preservation.

  2. Bone targeted therapies for the prevention of skeletal morbidity in men with prostate

    Directory of Open Access Journals (Sweden)

    Philip J Saylor

    2014-06-01

    Full Text Available Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-κ-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed.

  3. Preventing Bacterial Infections using Metal Oxides Nanocoatings on Bone Implant

    Science.gov (United States)

    Duceac, L. D.; Straticiuc, S.; Hanganu, E.; Stafie, L.; Calin, G.; Gavrilescu, S. L.

    2017-06-01

    Nowadays bone implant removal is caused by infection that occurs around it possibly acquired after surgery or during hospitalization. The purpose of this study was to reveal some metal oxides applied as coatings on bone implant thus limiting the usual antibiotics-resistant bacteria colonization. Therefore ZnO, TiO2 and CuO were synthesized and structurally and morphologically analized in order to use them as an alternative antimicrobial agents deposited on bone implant. XRD, SEM, and FTIR characterization techniques were used to identify structure and texture of these nanoscaled metal oxides. These metal oxides nanocoatings on implant surface play a big role in preventing bacterial infection and reducing surgical complications.

  4. Treatment of bone loss in osteopenic patients with Crohn's disease: a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation

    NARCIS (Netherlands)

    van Bodegraven, A.A.; Bravenboer, N.; Witte, B.I.; Dijkstra, G.; van der Woude, C.J.; Stokkers, P.C.M.; Russel, M.G.; Oldenburg, B.; Pierik, M.; Roos, J.C.; van Hogezand, R.A.; Dik, V.K.; Oostlander, A.E.; Netelenbos, J.C.; van de Langerijt, L.; Hommes, D.W.; Lips, P.T.A.M.

    2014-01-01

    Objective: Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a

  5. Effects of COLIA1 polymorphisms and haplotypes on perimenopausal bone mass, postmenopausal bone loss and fracture risk

    DEFF Research Database (Denmark)

    González-Bofill, N; Husted, Camilla L.; Harsløf, Torben

    2011-01-01

    mineral density (BMD) and increased bone turnover at menopause and after 10 years of follow-up. Introduction We wanted to investigate whether the -1997G/T, -1663indelT and +1245G/T polymorphisms in the COLIA1 gene are associated with perimenopausal bone mass, early postmenopausal bone loss and interact.......015±0.006 g/cm2 and 0.017±0.006 g/cm2, respectively (pchanges in bone mass and fracture risk and no overall interaction with the effects of hormone therapy could be demonstrated for any of the polymorphisms in COLIA1. Conclusions The -1997G/T polymorphism...... and haplotype 3 are significantly associated with perimenopausal bone mass, and these effects were sustained up to 10 years after menopause. No association between the -1663indelT or +1245G/T polymorphisms and peri- or postmenopausal bone mass could be demonstrated....

  6. AICRG, Part II: Crestal bone loss associated with the Ankylos implant: loading to 36 months.

    Science.gov (United States)

    Chou, Cherng-Tzeh; Morris, Harold F; Ochi, Shigeru; Walker, Lori; DesRosiers, Deborah

    2004-01-01

    The Ankylos endosseous dental implant is a new implant design that will be available in the United States in early 2004. It features an internal tapered abutment connection, a smooth polished collar without threads at the coronal part of the implant body, and a roughened surface with variable threads on the body of the implant fixture. A precise, tapered, conical abutment connection eliminates the microgap often found in 2-stage implant systems. This microgap may allow the accumulation of food debris and bacteria, as well as micromovement between the parts during clinical function, both of which can lead to a localized inflammation and crestal bone loss. The purpose of this section of the study was to assess any crestal bone loss associated with this new implant. The clinical performance of this new implant design was studied under well-controlled clinical conditions. Over 1500 implants were placed and restored. The vertical crestal bone loss was measured "directly" between the time of implant placement and uncovering, using a periodontal probe. Serial dental radiographs were taken between loading, and the 12-, 24-, and 36-month follow-up visits to determine "indirect" crestal bone loss within a specific period. Bone loss varied among the participating centers from less than 0.5 mm to 2.0 mm. The largest amount of bone loss occurred between the time of placement and uncovering. Following loading, the mean bone loss for all implants for a period of 3 years was about 0.2 mm/y. The extent of the crestal bone loss after loading was minimal for patients regardless of age, gender, prosthetic applications, bone density, and remote or crestal incisions, as well as for smokers or nonsmokers. Bone loss per year is well within the guidelines of 0.2 mm/y proposed by others.

  7. Combined Effects of Phytoestrogen Genistein and Silicon on Ovariectomy-Induced Bone Loss in Rat.

    Science.gov (United States)

    Qi, Shanshan; Zheng, Hongxing

    2017-06-01

    This study was performed to evaluate the effect of concomitant supplementation of genistein and silicon on bone mineral density and bone metabolism-related markers in ovariectomized rat. Three-month-old Sprague Dawley female rats were subjected to bilateral ovariectomy (OVX) or sham surgery, and then the OVX rats were randomly divided into four groups: OVX-GEN, OVX-Si, OVX-GEN-Si, and OVX. Genistein and silicon supplementation was started immediately after OVX and continued for 10 weeks. In the OVX-GEN group, 5 mg genistein per gram body weight was injected subcutaneously. The OVX-Si group was given soluble silicon daily in demineralized water (Si 20 mg/kg body weight/day). The OVX-GEN-Si group was given subcutaneous injections of 5 mg genistein per gram body weight, at the same time, given soluble silicon daily (Si 20 mg/kg body weight/day). The results showed that the genistein supplementation in the OVX rats significantly prevented the loss of uterus weight; however, the silicon supplementation showed no effect on the uterus weight loss. The lumbar spine and femur bone mineral density was significantly decreased after OVX surgery; however, this decrease was inhibited by the genistein and/or silicon, and the BMD of the lumbar spine and femur was the highest in the OVX-GEN-Si-treated group. Histomorphometric analyses showed that the supplementation of genistein and/or silicon restored bone volume and trabecular thickness of femoral trabecular bone in the OVX group. Besides, the treatment with genistein and silicon for 10 weeks increased the serum levels of calcium and phosphorus in the OVX rats; serum calcium and serum phosphorus in the OVX-GEN-Si group were higher than those in the OVX-GEN and OVX-Si group (P silicon decreased serum alkaline phosphatase (ALP) and osteocalcin, which were increased by ovariectomy; serum ALP and osteocalcin in the OVX-GEN-Si group were lower than those in the OVX-GEN and OVX-Si groups (P silicon have synergistic effects on

  8. Tracking changes and preventing loss in critical tiger habitat.

    Science.gov (United States)

    Joshi, Anup R; Dinerstein, Eric; Wikramanayake, Eric; Anderson, Michael L; Olson, David; Jones, Benjamin S; Seidensticker, John; Lumpkin, Susan; Hansen, Matthew C; Sizer, Nigel C; Davis, Crystal L; Palminteri, Suzanne; Hahn, Nathan R

    2016-04-01

    The global population of wild tigers remains dangerously low at fewer than 3500 individuals. Habitat loss, along with poaching, can undermine the international target recovery of doubling the number of wild tigers by 2022. Using a new satellite-based monitoring system, we analyzed 14 years of forest loss data within the 76 landscapes (ranging from 278 to 269,983 km(2)) that have been prioritized for conservation of wild tigers. Our analysis provides an update of the status of tiger habitat and describes new applications of technology to detect precisely where forest loss is occurring in order to curb future habitat loss. Across the 76 landscapes, forest loss was far less than anticipated (79,597 ± 22,629 km(2), 7.7% of remaining habitat) over the 14-year study period (2001-2014). Habitat loss was unevenly distributed within a subset of 29 landscapes deemed most critical for doubling wild tiger populations: 19 showed little change (1.5%), whereas 10 accounted for more than 98% (57,392 ± 16,316 km(2)) of habitat loss. Habitat loss in source population sites within 76 landscapes ranged from no loss to 435 ± 124 km(2) ([Formula: see text], SD = 89, total = 1676 ± 476 km(2)). Doubling the tiger population by 2022 requires moving beyond tracking annual changes in habitat. We highlight near-real-time forest monitoring technologies that provide alerts of forest loss at relevant spatial and temporal scales to prevent further erosion.

  9. The effect of peri-implant bone exposure on soft tissue healing and bone loss in two adjacent implants

    Science.gov (United States)

    Shin, Seung-Yun; Kye, Seung-Boem; Hong, Jongrak; Paeng, Jun-Young

    2012-01-01

    Purpose The purpose of this study was to evaluate the soft tissue and bone change around two adjacent implants in one-stage implant surgery. Methods Eleven subjects (7 males, 4 females) who were needed placement of 2 adjacent implants in the molar area were included. The two implants were placed with the platform at the level of the alveolar crest. The interproximal bone between the 2 implants was not covered with gingiva. After surgery, an alginate impression was taken to record the gingival shape and radiographs were taken to evaluate implant placement. Using a master cast, the gingival height was measured at baseline, 4 weeks, and 12 weeks. In the radiograph, the alveolar bone level was measured at the mesial and distal side of both implants at baseline and 12 weeks. Results The exposed bone was covered with gingiva at both 4 and 12 weeks. Loss of alveolar bone around implants was found in all areas. The alveolar bone level in the exposed bone area did not differ from that in the non-exposed area. Conclusions This study showed that the alveolar bone level and gingival height around 2 adjacent implants in the exposed bone area did not differ from that in unexposed bone area. PMID:22413070

  10. The Use of Structural Allograft in Primary and Revision Knee Arthroplasty with Bone Loss

    Directory of Open Access Journals (Sweden)

    Raul A. Kuchinad

    2011-01-01

    Full Text Available Bone loss around the knee in the setting of total knee arthroplasty remains a difficult and challenging problem for orthopaedic surgeons. There are a number of options for dealing with smaller and contained bone loss; however, massive segmental bone loss has fewer options. Small, contained defects can be treated with cement, morselized autograft/allograft or metal augments. Segmental bone loss cannot be dealt with through simple addition of cement, morselized autograft/allograft, or metal augments. For younger or higher demand patients, the use of allograft is a good option as it provides a durable construct with high rates of union while restoring bone stock for future revisions. Older patients, or those who are low demand, may be better candidates for a tumour prosthesis, which provides immediate ability to weight bear and mobilize.

  11. Bone loss at implants and teeth in the same inter-proximal unit: A radiographic study.

    Science.gov (United States)

    Cecchinato, Denis; Marino, Massimiliano; Toia, Marco; Cecchinato, Francesca; Lindhe, Jan

    2018-02-10

    This study was performed to determine whether the distance between an implant and a tooth present in an inter-proximal unit influenced the amount of marginal bone loss that occurred at the two facing (adjacent) surfaces. One hundred and eighty patients with a total of 278 inter-proximal units were included. Radiographs of implants that also included adjacent (facing) natural tooth/teeth were digitalized, and various linear measurements were performed using a software program. The marginal bone level and the bone level change that had occurred during a mean of 5.8 years were assessed as well as distance between the implant and the adjacent tooth/teeth. The mean amount of additional marginal bone loss that took place during the observation period was about 0.4 mm at both implants and adjacent tooth surfaces. The horizontal distance between an implant and the facing tooth did not influence the amount of marginal bone loss that had occurred. In most inter-proximal units, more advanced bone loss (>1 mm, >2 mm) had ensued either at the implant or at the facing tooth surface. Advanced additional bone loss occurred at both the implant and the tooth in only about 3% of the examined subjects. Bone loss at implants and teeth appears to be a site-specific phenomenon and not dependent on the inter-proximal distance. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. The combined effects of soya isoflavones and resistant starch on equol production and trabecular bone loss in ovariectomised mice.

    Science.gov (United States)

    Tousen, Yuko; Matsumoto, Yu; Matsumoto, Chiho; Nishide, Yoriko; Nagahata, Yuya; Kobayashi, Isao; Ishimi, Yoshiko

    2016-07-01

    Equol is a metabolite of the soya isoflavone (ISO) daidzein that is produced by intestinal microbiota. Equol has greater oestrogenic activity compared with other ISO, and it prevents bone loss in postmenopausal women. Resistant starch (RS), which has a prebiotic activity and is a dietary fibre, was reported to promote equol production. Conversely, the intestinal microbiota is reported to directly regulate bone health by reducing inflammatory cytokine levels and T-lymphocytes in bone. The present study evaluated the combined effects of diet supplemented with ISO and RS on intestinal microbiota, equol production, bone mineral density (BMD) and inflammatory gene expression in the bone marrow of ovariectomised (OVX) mice. Female ddY strain mice, aged 8 weeks, were either sham-operated (Sham, n 7) or OVX. OVX mice were randomly divided into the following four groups (seven per group): OVX control (OVX); OVX fed 0·05 % ISO diet (OVX+ISO); OVX fed 9 % RS diet (OVX+RS); and OVX fed 0·05 % ISO- and 9 % RS diet (OVX+ISO+RS). After 6 weeks, treatment with the combination of ISO and RS increased equol production, prevented the OVX-induced decline in trabecular BMD in the distal femur by modulating the enteric environment and altered OVX-induced inflammation-related gene expression in the bone marrow. However, there were no significant differences in bone parameters between the ISO+RS and ISO-alone groups in OVX mice. Our findings suggest that the combination of ISO and RS might alter intestinal microbiota and immune status in the bone marrow, resulting in attenuated bone resorption in OVX mice.

  13. Chronic Alcohol Abuse Leads to Low Bone Mass with No General Loss of Bone Structure or Bone Mechanical Strength

    DEFF Research Database (Denmark)

    Ulhøi, Maiken Parm; Meldgaard, Karoline; Steiniche, Torben

    2017-01-01

    Chronic alcohol abuse (CAA) has deleterious effects on skeletal health. This study examined the impact of CAA on bone with regard to bone density, structure, and strength. Bone specimens from 42 individuals with CAA and 42 individuals without alcohol abuse were obtained at autopsy. Dual-energy X...... wall thickness of trabecular osteons compared to individuals without alcohol abuse. No significant difference was found for bone strength and structure. Conclusion: CAA leads to low bone mass due to a decrease in bone formation but with no destruction of bone architecture nor a decrease in bone...

  14. Bisphosphonates inhibit pain, bone loss, and inflammation in a rat tibia fracture model of complex regional pain syndrome

    Science.gov (United States)

    Wang, Liping; Guo, Tian-Zhi; Wei, Tzuping; Li, Wen-wu; Shi, Xiaoyou; Clark, J David; Kingery, Wade S

    2016-01-01

    BACKGROUND Bisphosphonates are used to prevent the bone loss and fractures associated with osteoporosis, bone metastases, multiple myeloma, and osteogenis deformans. Distal limb fractures cause regional bone loss with cutaneous inflammation and pain in the injured limb that can develop into complex regional pain syndrome (CRPS). Clinical trials have reported that anti-resorptive bisphosphonates can prevent fracture-induced bone loss, inhibit serum inflammatory cytokine levels, and alleviate CRPS pain. Previously we observed that the inhibition of inflammatory cytokines or adaptive immune responses attenuated the development of pain behavior in a rat fracture model of CRPS and we hypothesized that bisphosphonates could prevent pain behavior, trabecular bone loss, post-fracture cutaneous cytokine up-regulation, and adaptive immune responses in this CRPS model. METHODS Rats underwent tibia fracture and cast immobilization for 4 weeks and were chronically administered either subcutaneously perfused alendronate or oral zoledronate. Behavioral measurements included hindpaw von Frey allodynia, unweighting, warmth, and edema. Bone microarchitecture was measured by uCT and bone cellular activity was evaluated by static and dynamic histomorphometry. Spinal cord Fos immunostaining was performed and skin cytokine (TNF, IL-1, IL-6) and nerve growth factor (NGF) levels were determined by EIA. Skin and sciatic nerve immunoglobulin levels were determined by EIA. RESULTS Tibia fracture rats developed hindpaw allodynia, unweighting, warmth, and edema, increased spinal Fos expression, trabecular bone loss in the lumbar vertebra and bilateral distal femurs as measured by uCT, increased trabecular bone resorption and osteoclast surface with decreased bone formation rates, increased cutaneous inflammatory cytokine and NGF expression and elevated immunocomplex deposition in skin and nerve. Alendronate (60 μg/kg/day s.c.) or zoledronate (3 mg/kg/day p.o.) treatment for 28 days, started

  15. Bisphosphonates Inhibit Pain, Bone Loss, and Inflammation in a Rat Tibia Fracture Model of Complex Regional Pain Syndrome.

    Science.gov (United States)

    Wang, Liping; Guo, Tian-Zhi; Hou, Saiyun; Wei, Tzuping; Li, Wen-Wu; Shi, Xiaoyou; Clark, J David; Kingery, Wade S

    2016-10-01

    Bisphosphonates are used to prevent the bone loss and fractures associated with osteoporosis, bone metastases, multiple myeloma, and osteogenesis deformans. Distal limb fractures cause regional bone loss with cutaneous inflammation and pain in the injured limb that can develop into complex regional pain syndrome (CRPS). Clinical trials have reported that antiresorptive bisphosphonates can prevent fracture-induced bone loss, inhibit serum inflammatory cytokine levels, and alleviate CRPS pain. Previously, we observed that the inhibition of inflammatory cytokines or adaptive immune responses attenuated the development of pain behavior in a rat fracture model of CRPS, and we hypothesized that bisphosphonates could prevent pain behavior, trabecular bone loss, postfracture cutaneous cytokine upregulation, and adaptive immune responses in this CRPS model. Rats underwent tibia fracture and cast immobilization for 4 weeks and were chronically administered either subcutaneously perfused alendronate or oral zoledronate. Behavioral measurements included hindpaw von Frey allodynia, unweighting, warmth, and edema. Bone microarchitecture was measured by microcomputed tomography, and bone cellular activity was evaluated by static and dynamic histomorphometry. Spinal cord Fos immunostaining was performed, and skin cytokine (tumor necrosis factor, interleukin [IL]-1, IL-6) and nerve growth factor (NGF) levels were determined by enzyme immunoassay. Skin and sciatic nerve immunoglobulin levels were determined by enzyme immunoassay. Rats with tibia fractures developed hindpaw allodynia, unweighting, warmth, and edema, increased spinal Fos expression and trabecular bone loss in the lumbar vertebra and bilateral distal femurs as measured by microcomputed tomography, increased trabecular bone resorption and osteoclast surface with decreased bone formation rates, increased cutaneous inflammatory cytokine and NGF expression, and elevated immunocomplex deposition in skin and nerve

  16. Chronic Alcohol Abuse Leads to Low Bone Mass with No General Loss of Bone Structure or Bone Mechanical Strength.

    Science.gov (United States)

    Ulhøi, Maiken Parm; Meldgaard, Karoline; Steiniche, Torben; Odgaard, Anders; Vesterby, Annie

    2017-01-01

    Chronic alcohol abuse (CAA) has deleterious effects on skeletal health. This study examined the impact of CAA on bone with regard to bone density, structure, and strength. Bone specimens from 42 individuals with CAA and 42 individuals without alcohol abuse were obtained at autopsy. Dual-energy X-ray absorptiometry (DEXA), compression testing, ashing, and bone histomorphometry were performed. Individuals with CAA had significantly lower bone mineral density (BMD) in the femoral neck and significantly lower bone volume demonstrated by thinner trabeculae, decreased extent of osteoid surfaces, and lower mean wall thickness of trabecular osteons compared to individuals without alcohol abuse. No significant difference was found for bone strength and structure. CAA leads to low bone mass due to a decrease in bone formation but with no destruction of bone architecture nor a decrease in bone strength. It is questionable whether this per se increases fracture risk. © 2016 American Academy of Forensic Sciences.

  17. Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

    Science.gov (United States)

    Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

    2012-01-01

    Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

  18. Male Astronauts Have Greater Bone Loss and Risk of Hip Fracture Following Long Duration Spaceflights than Females

    Science.gov (United States)

    Ellman, Rachel; Sibonga, Jean; Bouxsein, Mary

    2010-01-01

    This slide presentation reviews bone loss in males and compares it to female bone loss during long duration spaceflight. The study indicates that males suffer greater bone loss than females and have a greater risk of hip fracture. Two possible reason for the greater male bone loss are that the pre-menopausal females have the estrogen protection and the greater strength of men max out the exercise equipment that provide a limited resistance to 135 kg.

  19. Monoaxial distraction of ulna to second metacarpal followed by single bone forearm in massive post infective radial bone loss

    Directory of Open Access Journals (Sweden)

    Jitendra N Pal

    2012-01-01

    Full Text Available Introduction: Radial bone loss associated with gross manus valgus deformity can be managed by open reduction internal fixation using intervening strut bone graft, callus distraction using ring or monoaxial fixator, and achieving union by distraction histogenesis. These methods are particularly suitable when bone loss is small. Single or staged procedure is described for congenital as well as in acquired extensive bone loss of radius. Distraction through radial proximal to distal segments, to achieve reduction of distal radio-ulnar joint (DRUJ, is also described in acquired cases. In the present series, functional results of distraction through ulna to 2 nd metacarpal is studied alongwith, functional status of hand, stability of wrist, level of patient′s satisfaction are also studied. Materials and Methods: 7 unilateral cases of radial loss (M = 5, F = 2 affecting 4 right hands of mean age 17 years (range 9 to 24 years were included in this study. They were treated by distracting through ulna to 2 nd metacarpal to achieve DRUJ alignment in first stage. Subsequently ulna was osteotomised and translated to distal stump of radius. It was then fixed to the distal radial remnant in 30° pronation in dominant and 30° supination non dominant hands. Results: Union was achieved in all cases associated with beneficial cross union of distal ulna. Hand functions improved near to normal, with fully corrected stable wrist joint, hypertrophied ulna and without recurrence. All of them had practically complete loss of forearm rotations, however patients were fully satisfied. Conclusion: This method is particularly suitable when associated with 6 cm or more radial bone loss. But when loss is small, sacrifice of one bone may not be justifiable.

  20. Interventions to prevent occupational noise-induced hearing loss

    NARCIS (Netherlands)

    Tikka, Christina; Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wouter A.; Ferrite, Silvia

    2017-01-01

    This is the second update of a Cochrane Review originally published in 2009. Millions of workers worldwide are exposed to noise levels that increase their risk of hearing disorders. There is uncertainty about the effectiveness of hearing loss prevention interventions. To assess the effectiveness of

  1. Prevention of Bone Metastases in Breast Cancer Patients. Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Philippe Beuzeboc

    2014-05-01

    Full Text Available One in four breast cancer patients is at risk of developing bone metastases in her life time. The early prevention of bone metastases is a crucial challenge. It has been suggested that the use of zoledronic acid (ZOL in the adjuvant setting may reduce the persistence of disseminated tumor cells and thereby might improve outcome, specifically in a population of patients with a low estrogen microenvironment. More recently, the results of a large meta-analysis from 41 randomized trials comparing a bisphosphonate (BP to placebo or to an open control have been presented at the 2013 San Antonio Breast Cancer Meeting. Data on 17,016 patients confirm that adjuvant BPs, irrespective of the type of treatment or the treatment schedule and formulation (oral or intra-venously (IV, significantly reduced bone recurrences and improved breast cancer survival in postmenopausal women. No advantage was seen in premenopausal women. BPs are soon likely to become integrated into standard practice. Published data on the mechanisms involved in tumor cell seeding from the primary site, in homing to bone tissues and in the reactivation of dormant tumor cells will be reviewed; these might offer new ideas for innovative combination strategies.

  2. Bone marrow mesenchymal stem cells protect against retinal ganglion cell loss in aged rats with glaucoma

    Directory of Open Access Journals (Sweden)

    Hu Y

    2013-10-01

    Full Text Available Ying Hu,1,2 Hai Bo Tan,1 Xin Mei Wang,3 Hua Rong,1 Hong Ping Cui,1 Hao Cui2 Departments of Ophthalmology, 1Shanghai East Hospital of Tongji University, Shanghai, 2First Affiliated Hospital, 3Fourth Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China Abstract: Glaucoma is a common eye disease in the aged population and has severe consequences. The present study examined the therapeutic effects of bone marrow mesenchymal stem cell (BMSC transplantation in preventing loss of visual function in aged rats with glaucoma caused by laser-induced ocular hypertension. We found that BMSCs promoted survival of retinal ganglion cells in the transplanted eye as compared with the control eye. Further, in swimming tests guided by visual cues, the rats with a BMSC transplant performed significantly better. We believe that BMSC transplantation therapy is effective in treating aged rats with glaucoma. Keywords: glaucoma, stem cell, transplantation, cell therapy, aging

  3. Buccal bone loss after immediate implantation can be reduced by the flapless approach

    Directory of Open Access Journals (Sweden)

    ARTHUR BELÉM NOVAES JR

    2011-10-01

    Full Text Available Aim: The aim of this study was to evaluate the buccal bone remodeling after immediate implantation with flap or flapless approach. Material and Methods: The mandibular bilateral premolars of 3 dogs were extracted and immediately three implants were placed in both hemi-arches of each dog. Randomly, one hemi-arch was treated with the flapless approach, while in the contra lateral hemi-arch tooth extractions and implant placement were done after mucoperiosteal flap elevation. Non-submerged healing of 12 weeks was provided for both groups. Histomorphometric analysis was done to compare buccal and lingual bone height loss, bone density and bone-to-implant contact in the groups. Fluorescence analysis was performed to investigate the dynamic of bone remodeling in the different groups. Results: There was a significant association between the surgical flap and the extent of bone resorption around immediate implants. The loss of buccal bone height was significantly lower in the flapless group when compared to the flap group (0.98 mm x 2.14 mm, respectively, p<0.05. The coronal and apical buccal bone densities of the flap group were significantly higher when compared to the lingual components, showing anatomical differences between the bone plates. Fluorescence analysis showed no major differences in bone healing between the flap and flapless groups, supporting that the higher loss of buccal bone height is linked to the anatomic characteristics of this plate and to the negative influence of the detachment of the periosteum in immediate implant therapy. Conclusion: The flapless approach for immediate post-extraction implants reduces the buccal bone height loss.

  4. Differential roles of MAPK kinases MKK3 and MKK6 in osteoclastogenesis and bone loss.

    Directory of Open Access Journals (Sweden)

    David L Boyle

    Full Text Available Bone mass is maintained by osteoclasts that resorb bone and osteoblasts that promote matrix deposition and mineralization. Bone homeostasis is altered in chronic inflammation as well as in post-menopausal loss of estrogen, which favors osteoclast activity that leads to osteoporosis. The MAPK p38α is a key regulator of bone loss and p38 inhibitors preserve bone mass by inhibiting osteoclastogenesis. p38 function is regulated by two upstream MAPK kinases, namely MKK3 and MKK6. The goal of this study was to assess the effect of MKK3- or MKK6-deficiency on osteoclastogenesis in vitro and on bone loss in ovariectomy-induced osteoporosis in mice. We demonstrated that MKK3 but not MKK6, regulates osteoclast differentiation from bone marrow cells in vitro. Expression of NFATc1, a master transcription factor in osteoclastogenesis, is decreased in cells lacking MKK3 but not MKK6. Expression of osteoclast-specific genes Cathepsin K, osteoclast-associated receptor and MMP9, was inhibited in MKK3-/- cells. The effect of MKK-deficiency on ovariectomy-induced bone loss was then evaluated in female WT, MKK3-/- and MKK6-/- mice by micro-CT analysis. Bone loss was partially inhibited in MKK3-/- as well as MKK6-/- mice, despite normal osteoclastogenesis in MKK6-/- cells. This correlated with the lower osteoclast numbers in the MKK-deficient ovariectomized mice. These studies suggest that MKK3 and MKK6 differentially regulate bone loss due to estrogen withdrawal. MKK3 directly mediates osteoclastogenesis while MKK6 likely contributes to pro-inflammatory cytokine production that promotes osteoclast formation.

  5. The clinical and radiological assessment of periodontal bone loss treatment using Emdogain.

    Science.gov (United States)

    Tokajuk, G; Pawińska, M; Kedra, B A

    2006-01-01

    ADMISSION: Emdogain is the only one biomaterial using biomicra effect which is practiced in periodontal surgery. The purpose of the study was a clinical and radiological assessment of bone loss treatment using Emdogain. There were 19 persons examined (11 women and 8 men) which have bone loss treated. Initial and monitoring examination after 10 months embraced clinical parameters such as PPD, CAL and radiological--based on intraoral x-ray pictures. Emdogain treatment was made according to surgical procedures. The research has shown reduction of the depth of periodontal pockets average about 3.4 mm and attachment connective tissue growth about 2.2 mm. Bone loss filling was on 67.1% level. Bone loss filling and growth of connective tissue attachment are in our research lower than in most of the others publications. Our observation concerned 10 months period so we should expect better effects after longer time. MOTIONS: Emdogain is safe and effective regeneration material.

  6. Effect of dietary soy isoflavones on bone loss in ovariectomized rats ...

    African Journals Online (AJOL)

    Purpose: To determine the effect of dietary soy isoflavone supplementation on bone loss in ovariectomized (OVX) rats. Methods: Forty-eight rats were assigned randomly to groups of OVX rats receiving soy isoflavones (20, 30, or 40 mg/kg of body weight daily), untreated OVX rats, or untreated intact rats. After 8 weeks, bone ...

  7. Vitamin K’s role in age-related bone loss: A critical review

    Science.gov (United States)

    The protective role of vitamin K in age-related bone loss continues to be controversial. The results of observational analyses are inconsistent with respect to associations between vitamin K status and bone, which arguably may be related to the limitations of observational study designs and analyt...

  8. The Ovariectomized Rat as a Model for Studying Alveolar Bone Loss in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Bryan D. Johnston

    2015-01-01

    Full Text Available In postmenopausal women, reduced bone mineral density at the hip and spine is associated with an increased risk of tooth loss, possibly due to a loss of alveolar bone. In turn, having fewer natural teeth may lead to compromised food choices resulting in a poor diet that can contribute to chronic disease risk. The tight link between alveolar bone preservation, tooth retention, better nutritional status, and reduced risk of developing a chronic disease begins with the mitigation of postmenopausal bone loss. The ovariectomized rat, a widely used preclinical model for studying postmenopausal bone loss that mimics deterioration of bone tissue in the hip and spine, can also be used to study mineral and structural changes in alveolar bone to develop drug and/or dietary strategies aimed at tooth retention. This review discusses key findings from studies investigating mandible health and alveolar bone in the ovariectomized rat model. Considerations to maximize the benefits of this model are also included. These include the measurement techniques used, the age at ovariectomy, the duration that a rat is studied after ovariectomy and habitual diet consumed.

  9. COMPARSION BETWEEN PANORAMIC PERIAPICAL AND VERTICAL BITEWING RADIOGRAPHY IN DIAGNOSIS OF PERIODONTAL BONE LOSS

    Directory of Open Access Journals (Sweden)

    M SHEIKHI

    2000-09-01

    Full Text Available Introduction. For diagnosis and treatment planing and detection the quality of remaining Alveolar bone the radiography is very useful so the type of radiography is very important. The purpose of this study is the comparison between panoramic, periapical (bisecting technique and vertical bitewing radiographs in diagnosis of periodontitis. Methods. Twelve patients (3 male and 9 female with a mean age of 35, with a moderate to advanced periodontitis were evaluated. At the time of periodontal surgery, in the posterior site of two jaws (in 6 and 7 teeth, the bone loss was measured from CEJ to the base of alveolar bone, and compared with the radiographic findings of proximal bone loss. Results. The average of distance between CEJ and alveolar bone in 48 surfaces were 4.27 in clinic, 4.80 in panoramic, 2.62 in periapical (bisecting technique, 2.98 in vertical bitewing and 4.05 in panoramic without magnification. Discussion. In this research we cancluded that both techniques (periapical and vertical bitewing are not accurate in detection of proximal bone loss and there was significant difference between quantity of proximal bone in clinical measurment than radiographic measurment and this study showed that the panoramic (specially panoramic without magnification is more careful than other radiographic techniques in detection of proximal bone loss.

  10. Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy

    DEFF Research Database (Denmark)

    Hoy, Jennifer F; Grund, Birgit; Roediger, Mollie P

    2017-01-01

    Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect ...

  11. Tracking changes and preventing loss in critical tiger habitat

    Science.gov (United States)

    Joshi, Anup R.; Dinerstein, Eric; Wikramanayake, Eric; Anderson, Michael L.; Olson, David; Jones, Benjamin S.; Seidensticker, John; Lumpkin, Susan; Hansen, Matthew C.; Sizer, Nigel C.; Davis, Crystal L.; Palminteri, Suzanne; Hahn, Nathan R.

    2016-01-01

    The global population of wild tigers remains dangerously low at fewer than 3500 individuals. Habitat loss, along with poaching, can undermine the international target recovery of doubling the number of wild tigers by 2022. Using a new satellite-based monitoring system, we analyzed 14 years of forest loss data within the 76 landscapes (ranging from 278 to 269,983 km2) that have been prioritized for conservation of wild tigers. Our analysis provides an update of the status of tiger habitat and describes new applications of technology to detect precisely where forest loss is occurring in order to curb future habitat loss. Across the 76 landscapes, forest loss was far less than anticipated (79,597 ± 22,629 km2, 7.7% of remaining habitat) over the 14-year study period (2001–2014). Habitat loss was unevenly distributed within a subset of 29 landscapes deemed most critical for doubling wild tiger populations: 19 showed little change (1.5%), whereas 10 accounted for more than 98% (57,392 ± 16,316 km2) of habitat loss. Habitat loss in source population sites within 76 landscapes ranged from no loss to 435 ± 124 km2 (x¯=24km2, SD = 89, total = 1676 ± 476 km2). Doubling the tiger population by 2022 requires moving beyond tracking annual changes in habitat. We highlight near–real-time forest monitoring technologies that provide alerts of forest loss at relevant spatial and temporal scales to prevent further erosion. PMID:27051881

  12. The influence of smoking on bone loss and response to nasal estradiol

    DEFF Research Database (Denmark)

    Bjarnason, N.H.; Nielsen, T.F.; Jørgensen, Henrik Løvendahl

    2009-01-01

    Objective To investigate the influence of smoking on bone during therapy with nasally administrated estradiol in sequential combination with oral progesterone in early postmenopausal women. In addition, to observe the consequences of smoking on bone in untreated women. Methods Post-hoc explorator...... estradiol to increase bone mass in early postmenopausal women. In addition, smoking may increase spontaneous bone loss in untreated women Udgivelsesdato: 2009......Objective To investigate the influence of smoking on bone during therapy with nasally administrated estradiol in sequential combination with oral progesterone in early postmenopausal women. In addition, to observe the consequences of smoking on bone in untreated women. Methods Post-hoc exploratory...... analyses of data from 270 postmenopausal women randomized to 2 years' therapy with daily nasal administration of 17-estradiol or placebo sequentially combined with oral micronized progesterone in the active groups or placebo in the placebo group. Results During treatment with nasal estradiol, the bone...

  13. 15-deoxy-δ12,14-prostaglandin j2 inhibits osteolytic breast cancer bone metastasis and estrogen deficiency-induced bone loss.

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    Ki Rim Kim

    Full Text Available Breast cancer is the major cause of cancer death in women worldwide. The most common site of metastasis is bone. Bone metastases obstruct the normal bone remodeling process and aberrantly enhance osteoclast-mediated bone resorption, which results in osteolytic lesions. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 is an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPARγ that has anti-inflammatory and antitumor activity at micromolar concentrations through PPARγ-dependent and/or PPARγ-independent pathways. We investigated the inhibitory activity of 15d-PGJ2 on the bone loss that is associated with breast cancer bone metastasis and estrogen deficiency caused by cancer treatment. 15d-PGJ2 dose-dependently inhibited viability, migration, invasion, and parathyroid hormone-related protein (PTHrP production in MDA-MB-231 breast cancer cells. 15d-PGJ2 suppressed receptor activator of nuclear factor kappa-B ligand (RANKL mRNA levels and normalized osteoprotegerin (OPG mRNA levels in hFOB1.19 osteoblastic cells treated with culture medium from MDA-MB-231 cells or PTHrP, which decreased the RANKL/OPG ratio. 15d-PGJ2 blocked RANKL-induced osteoclastogenesis and inhibited the formation of resorption pits by decreasing the activities of cathepsin K and matrix metalloproteinases, which are secreted by mature osteoclasts. 15d-PGJ2 exerted its effects on breast cancer and bone cells via PPARγ-independent pathways. In Balb/c nu/nu mice that received an intracardiac injection of MDA-MB-231 cells, subcutaneously injected 15d-PGJ2 substantially decreased metastatic progression, cancer cell-mediated bone destruction in femora, tibiae, and mandibles, and serum PTHrP levels. 15d-PGJ2 prevented the destruction of femoral trabecular structures in estrogen-deprived ICR mice as measured by bone morphometric parameters and serum biochemical data. Therefore, 15d-PGJ2 may be beneficial for the prevention and treatment of breast cancer

  14. Antiepileptic drug-induced bone loss in young male patients who have seizures.

    Science.gov (United States)

    Andress, Dennis L; Ozuna, Judy; Tirschwell, David; Grande, Lucinda; Johnson, Meshell; Jacobson, Arnold F; Spain, William

    2002-05-01

    Long-term antiepileptic drug (AED) therapy is a known risk factor for bone loss and fractures. Vitamin D deficiency is frequently cited as a cause for bone loss in patients who have seizures. To determine whether men who have seizures, but who are otherwise healthy, suffer substantial bone loss in the hip while taking AEDs. We prospectively examined femoral neck bone mineral density (BMD) by dual-energy x-ray absorptiometry in 81 consecutive men, aged between 25 and 54 years old (mean age, 45 years), who were attending an outpatient seizure clinic. Low BMD values were analyzed for known risk factors for bone loss. Dual-energy x-ray absorptiometry scans were repeated in 54 patients, 12 to 29 months later (mean, 19 months), to assess the rate of change in BMD over time. Multivariate linear regression analysis revealed that age (P<.001) and time receiving AEDs (P<.003) were the 2 important risk factors associated with low femoral neck BMD. Neither vitamin D deficiency, hypogonadism, cigarette smoking, nor excess alcohol intake were associated with low BMD after correcting for age and time on AEDs. Longitudinal analysis of femoral neck BMD revealed that only those in the youngest age group (25-44 years) showed significant declines in femoral neck BMD (1.8% annualized loss; 95% confidence interval, -3.1 to -0.9; P<.003) while receiving AED therapy. There was no evidence that a specific type of AED was more causally related to bone loss in this group although most patients were taking phenytoin sodium or carbamazepine during the longitudinal assessment. Long-term AED therapy in young male patients who have seizures causes significant bone loss at the hip in the absence of vitamin D deficiency. Dual-energy x-ray absorptiometry scanning of the hip is useful in identifying patients who are particularly susceptible to rapid bone loss while taking AEDs.

  15. 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.

  16. Pattern of alveolar bone loss and reliability of measurements with the radiographic technique

    Energy Technology Data Exchange (ETDEWEB)

    Rise, J.; Albandar, J.M.

    1988-01-01

    The purposes of this paper were to study the pattern of bone loss among different teeth at the individual level and to study the effect of using different aggregated units of analysis on measurement error. Bone loss was assessed in standardized periapical radiographs from 293 subjects (18-68 years), and the mean bone loss score for each tooth type was calculated. These were then correlated by means of factor analysis to study the bone loss pattern. Reliability (measurement error) was studied by the internal consistency and the test-retest methods. The pattern of bone loss showed a unidimensional pattern, indicating that any tooth will work equally well as a dependent variable for epidemiologic descriptive purposes. However, a more thorough analysis also showed a multidimensional pattern in terms of four dimensions, which correspond to four tooth groups: incisors, upper premolars, lower premolars and molars. The four dimensions accounted for 80% of the toal variance. The multidimensional pattern may be important for the modeling of bone loss; thus different models may explain the four dimension (indices) used as dependent variables. The reliability (internal consistency) of the four indices was satisfactory. By the test-retest method, reliability was higher when the more aggregated unit (the individual) was used.

  17. Pattern of alveolar bone loss and reliability of measurements with the radiographic technique

    International Nuclear Information System (INIS)

    Rise, J.; Albandar, J.M.

    1988-01-01

    The purposes of this paper were to study the pattern of bone loss among different teeth at the individual level and to study the effect of using different aggregated units of analysis on measurement error. Bone loss was assessed in standardized periapical radiographs from 293 subjects (18-68 years), and the mean bone loss score for each tooth type was calculated. These were then correlated by means of factor analysis to study the bone loss pattern. Reliability (measurement error) was studied by the internal consistency and the test-retest methods. The pattern of bone loss showed a unidimensional pattern, indicating that any tooth will work equally well as a dependent variable for epidemiologic descriptive purposes. However, a more thorough analysis also showed a multidimensional pattern in terms of four dimensions, which correspond to four tooth groups: incisors, upper premolars, lower premolars and molars. The four dimensions accounted for 80% of the toal variance. The multidimensional pattern may be important for the modeling of bone loss; thus different models may explain the four dimension (indices) used as dependent variables. The reliability (internal consistency) of the four indices was satisfactory. By the test-retest method, reliability was higher when the more aggregated unit (the individual) was used

  18. Ultraviolet light-irradiated photocrosslinkable chitosan hydrogel to prevent bone formation in both rat skull and fibula bone defects.

    Science.gov (United States)

    Tsuda, Yoshifumi; Hattori, Hidemi; Tanaka, Yoshihiro; Ishihara, Masayuki; Kishimoto, Satoko; Amako, Masatoshi; Arino, Hiroshi; Nemoto, Koichi

    2013-09-01

    In the field of orthopaedic surgery, an orthopaedic surgeon sometimes requires to suppress excessive bone formation, such as ectopic bone formation, ossifying myositis and radio-ulnar synostosis, etc. Ultraviolet (UV) light irradiation of a photocrosslinkable chitosan (Az-CH-LA) generates an insoluble hydrogel within 30 s. The purpose of this study was to evaluate the ability of the photocrosslinked chitosan hydrogel (PCH) to inhibit bone formation in an experimental model of bone defect. Rat calvarium and fibula were surgically injured and PCH was implanted into the resultant bone defects. The PCH implants significantly prevented bone formation in the bone defects during the 4 and 8 week observation periods. In the PCH-treated defects, fibrous tissues infiltrated by inflammatory cells were formed by day 7, completely filling the bone defects. In addition to these findings, expression of osteocalcin and runt-related gene 2 (RUNX2) mRNA, both markers of bone formation, was lower in the PCH-treated defects than in the controls. In contrast, collagen type 1α2 and α-smooth muscle actin (α-SMA) mRNA levels were significantly higher in the PCH-treated defects after 1 week. PCH stimulated the formation of fibrous tissue in bone defects while inhibiting bone formation. Thus, PCH might be a promising new therapeutic biomaterial for the prevention of bone formation in orthopaedic surgery. Copyright © 2012 John Wiley & Sons, Ltd.

  19. 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

  20. Disrupted bone remodeling leads to cochlear overgrowth and hearing loss in a mouse model of fibrous dysplasia.

    Directory of Open Access Journals (Sweden)

    Omar Akil

    Full Text Available Normal hearing requires exquisite cooperation between bony and sensorineural structures within the cochlea. For example, the inner ear secretes proteins such as osteoprotegrin (OPG that can prevent cochlear bone remodeling. Accordingly, diseases that affect bone regulation can also result in hearing loss. Patients with fibrous dysplasia develop trabecular bone overgrowth resulting in hearing loss if the lesions affect the temporal bones. Unfortunately, the mechanisms responsible for this hearing loss, which could be sensorineural and/or conductive, remain unclear. In this study, we used a unique transgenic mouse model of increased Gs G-protein coupled receptor (GPCR signaling induced by expression of an engineered receptor, Rs1, in osteoblastic cells. These ColI(2.3+/Rs1+ mice showed dramatic bone lesions that histologically and radiologically resembled fibrous dysplasia. We found that ColI(2.3+/Rs1+ mice showed progressive and severe conductive hearing loss. Ossicular chain impingement increased with the size and number of dysplastic lesions. While sensorineural structures were unaffected, ColI(2.3+/Rs1+ cochleae had abnormally high osteoclast activity, together with elevated tartrate resistant acid phosphatase (TRAP activity and receptor activator of nuclear factor kappa-B ligand (Rankl mRNA expression. ColI(2.3+/Rs1+ cochleae also showed decreased expression of Sclerostin (Sost, an antagonist of the Wnt signaling pathway that normally increases bone formation. The osteocyte canalicular networks of ColI(2.3+/Rs1+ cochleae were disrupted and showed abnormal osteocyte morphology. The osteocytes in the ColI(2.3+/Rs1+ cochleae showed increased expression of matrix metalloproteinase 13 (MMP-13 and TRAP, both of which can support osteocyte-mediated peri-lacunar remodeling. Thus, while the ossicular chain impingement is sufficient to account for the progressive hearing loss in fibrous dysplasia, the deregulation of bone remodeling extends to the

  1. Mammary tumorigenesis causes bone loss and dietary selenium supplementation does not affect such bone loss in male MMTV-PyMT mice

    Science.gov (United States)

    Cancer progression is accompanied by wasting that eventually results in cachexia characterized by significant weight loss and multi-organ functional failures. Limited clinical trials indicate that bone is adversely affected by cancer-associated wasting. To determine the effects of breast cancer on...

  2. Bone loss in women with type 1 diabetes

    DEFF Research Database (Denmark)

    tanderup joergensen, maj-britt; christensen, jesper olund; Svendsen, Ole Lander

    2015-01-01

    Background: Although osteoporosis has been investigated and debated in the diabetic population over the past decades, very little is known about the spontaneous changes in bone mineral density (BMD) and biochemical markers of bone turnover in pre- and postmenopausal type 1 diabetic (T1DM) women...... postmenopausal) were reexamined in 1997. Method: BMD was measured at femoral neck (f.n.), spine (L2 - L4), total body and forearm with DXA or SXA in 53 T1DM women. 4 years later a re-scan was carried out on 35 T1DM. Results: In premenopausal subjects a yearly decrease less than 1% at f.n., spine, forearm...... over time. Aim: To measure spontaneous changes in BMD and biochemical markers of bone turnover in pre- and postmenopausal T1DM women. Subjects: 53 T1DM women (31 premenopausal and 22 postmenopausal) from the outpatient clinic were enrolled in the study in 1993 and 35 (22 premenopausal, 13...

  3. Bone loss in the lower leg during 35 days of bed rest is predominantly from the cortical compartment

    OpenAIRE

    Rittweger, Joern; Mekjavić, Igor B.; Eiken, Ola; Pišot, Rado; Biolo, Gianni; Cirillo, Massimo; De Santo, Natale Gaspare; Bilancio, Giancarlo; Šimunič, Boštjan; Narici, Marco

    2013-01-01

    Immobilization-induced bone loss is usually greater in the epiphyses than in the diaphyses. The larger fraction of trabecular bone in the epiphyses than in the diaphyses offers an intuitive explanation to account for this phenomenon. However, recent evidence contradicts this notion and suggests that immobilization-induced bone loss from the distal tibia epiphysis is mainly from the cortical compartment. The aim of this study was to establish whether this pattern of bone loss was a general rul...

  4. Intervention to Prevent Child Custody Loss in Mothers with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Mary V. Seeman

    2012-01-01

    Full Text Available Depending on jurisdiction, time period studied, and specifics of the population, approximately 50 percent of mothers who suffer from schizophrenia lose custody of their children. The aim of this paper is to recommend interventions aimed at preventing unnecessary custody loss. This paper reviews the social work, nursing, psychology, psychiatry, and law literature on mental illness and custody loss, 2000–2011. Recommendations to mothers are to (a ensure family health (b prevent psychotic relapse, (c prepare in advance for crisis, (d document daily parenting activities, (e take advantage of available parenting resources, and f become knowledgeable about legal issues that pertain to mental health and custody. From a policy perspective, child protection and adult mental health agencies need to dissolve administrative barriers and collaborate. Access to appropriate services will help mothers with schizophrenia to care appropriately for their children and allow these children to grow and develop within their family and community.

  5. Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss

    DEFF Research Database (Denmark)

    Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

    2009-01-01

    Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of aging...... in vivo, leading to decreased ability to form and maintain bone homeostasis with age. In this review we summarize evidence of MSC involvement in age related bone loss and suggest new emerging targets for intervention....

  6. Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Maira L. Mendonça

    Full Text Available OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT and 21 controls (CG. Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01. Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%. The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005, but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity.

  7. Automatic methods for alveolar bone loss degree measurement in periodontitis periapical radiographs.

    Science.gov (United States)

    Lin, P L; Huang, P Y; Huang, P W

    2017-09-01

    Periodontitis involves progressive loss of alveolar bone around the teeth. Hence, automatic alveolar bone loss measurement in periapical radiographs can assist dentists in diagnosing such disease. In this paper, we propose an automatic length-based alveolar bone loss measurement system with emphasis on a cementoenamel junction (CEJ) localization method: CEJ_LG. The bone loss measurement system first adopts the methods TSLS and ABLifBm, which we presented previously, to extract teeth contours and bone loss areas from periodontitis radiograph images. It then applies the proposed methods to locate the positions of CEJ, alveolar crest (ALC), and apex of tooth root (APEX), respectively. Finally the system computes the ratio of the distance between the positions of CEJ and ALC to the distance between the positions of CEJ and APEX as the degree of bone loss for that tooth. The method CEJ_LG first obtains the gradient of the tooth image then detects the border between the lower enamel and dentin (EDB) from the gradient image. Finally, the method identifies a point on the tooth contour that is horizontally closest to the EDB. Experimental results on 18 tooth images segmented from 12 periodontitis periapical radiographs, including 8 views of upper-jaw teeth and 10 views of lower-jaw teeth, show that 53% of the localized CEJs are within 3 pixels deviation (∼ 0.15 mm) from the positions marked by dentists and 90% have deviation less than 9 pixels (∼ 0.44 mm). For degree of alveolar bone loss, more than half of the measurements using our system have deviation less than 10% from the ground truth, and all measurements using our system are within 25% deviation from the ground truth. Our results suggest that the proposed automatic system can effectively estimate degree of horizontal alveolar bone loss in periodontitis radiograph images. We believe that our proposed system, if implemented in routine clinical practice, can serve as a valuable tool for early and accurate

  8. Spaceflight-induced Bone Loss: Is there a Risk for Accelerated Osteoporosis after Return?

    Science.gov (United States)

    Sibonga, Jean

    2008-01-01

    The evidence-to to-date suggests that the rapid rate of site-specific bone loss in space, due to the unbalanced stimulation of bone resorption, may predispose crew members to irreversible changes in bone structure and microarchitecture. No analyses conducted in the postflight period to assess microarchitectural changes. There is no complete analysis of skeletal recovery in the postflight period to evaluate the structural changes that accompany increases in DXA aBMD. Postflight analyses based upon QCT scans performed on limited crew members indicate reductions in hip bone strength and incomplete recovery at 1 year. No recovery of trabecular vBMD after 1 year return (HRP IWG). Time course of bone loss in space unknown.

  9. Pharmacotherapies to manage bone loss-associated diseases: a quest for the perfect benefit-to-risk ratio.

    Science.gov (United States)

    Valverde, P

    2008-01-01

    In this review, benefits and side-effects of current and emerging therapies to treat and prevent pathological bone loss are described. Bisphosphonates are the antiresorptive compounds most widely used in the treatment of bone-loss associated diseases. They are generally well-tolerated although have recently been associated with osteonecrosis of the jaw and other complications. Therapies modulating estrogen receptor activation are indicated in the prevention and treatment of either breast cancer or osteoporosis in postmenopausal women. Thus, hormone replacement therapy is effective in prevention of osteoporosis, but its long-term use can increase the risk of breast cancer, stroke and embolism. Tamoxifen benefits all stages of breast cancer, but its use may lead to uterine cancer and thromboembolism. Raloxifene is approved in prevention of breast cancer and treatment of postmenopausal osteoporosis, but its use can increase the risk of fatal stroke. Aromatase inhibitors are superior to tamoxifen at advanced stages of disease and as adjuvants, but their use increase fracture incidence. Fulvestrant is as effective as aromatase inhibitors in the treatment of advanced breast cancer and does not cause bone fractures. Another antiresorptive available for the treatment of postmenopausal osteoporosis, Paget's disease and hypercalcemia is calcitonin, which also exhibits analgesic effects. A promising antiresorptive agent currently in clinical trials is denosumab. Aditional therapies for osteoporosis that decrease fracture risk consist of PTH-like anabolic agents and the dual action bone agent strontium ranelate. Antiseptics and antibiotics are used extensively in periodontal disease intervention to target bacterial biofilm, although host-directed therapies are also being developed.

  10. Premature loss of bone remodeling compartment canopies is associated with deficient bone formation

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Søe, Kent

    2011-01-01

    A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling, were proposed to be critical players in this mechanism. Here, we provide...... support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces....... Both cohorts showed almost 100% canopy coverage above resorbing osteoclasts, and only about 76% above bone forming surfaces. This indicates that BRC canopies are invariably associated with the early stage of the remodeling cycle, but may disappear later. Interestingly, in control and two thirds...

  11. Role of IL-17A signalling in psoriasis and associated bone loss.

    Science.gov (United States)

    Uluçkan, Özge; Wagner, Erwin F

    2016-01-01

    Inflammation is a physiological reaction to tissue injury, pathogen invasion and a natural response to various stress stimuli. Innate and adaptive immune cells are activated and recruited to the site of inflammation to suppress or promote inflammation. The recruitment and activation of immune cells is modulated by cytokines and chemokines, which are regulated by transcription factors, such as AP-1 (Fos/Jun), NF-kB, NFATs and STATs. Moreover, it is now appreciated that chronic inflammation can lead to systemic effects affecting the whole organism by mechanisms which are not well understood.Here we review our recent data obtained from the analyses of psoriasis patient samples as well as from AP-1 (Fos/Jun)-dependent, genetically engineered mouse models. The deletion of two AP-1 factors JunB and c-Jun in an inducible manner in adult mice, specifically in Keratin-5 expressing tissues, leads to a psoriasis-like disease. Importantly, the epidermal proteome of the mutant mice is comparable to psoriasis patient samples. Our analyses revealed that the activation of S100A8/A9-dependent C3 complement as well as a miR-21-dependent TIMP-3/TACE pathway leading to TNF-α shedding, are causally involved in disease development.Epidermal deletion of only JunB in mice leads to chronic skin inflammation with increased levels of pro-inflammatory cytokines and multi-organ involvement. Our recent findings show that chronic skin inflammation induces bone loss through systemic elevated IL-17A signalling. This novel mechanism involves inhibition of osteoblast-mediated bone formation by reduced Wnt signalling with no effect on RANKL-dependent osteoclastic bone resorption. These data have important translational implications; blocking of IL-17A signalling, which is already approved for the treatment of psoriasis, should also be considered to prevent the adverse skeletal consequences of chronic inflammatory diseases.

  12. Oral administration of 5-hydroxytryptophan aggravated periodontitis-induced alveolar bone loss in rats.

    Science.gov (United States)

    Li, Xianxian; Wu, Xiangnan; Ma, Yuanyuan; Hao, Zhichao; Chen, Shenyuan; Fu, Taozi; Chen, Helin; Wang, Hang

    2015-05-01

    5-Hydroxytryptophan (5-HTP) is the precursor of serotonin and 5-HTP has been widely used as a dietary supplement to raise serotonin level. Serotonin has recently been discovered to be a novel and important player in bone metabolism. As peripheral serotonin negatively regulates bone, the regular take of 5-HTP may affect the alveolar bone metabolism and therefore influence the alveolar bone loss induced by periodontitis. The aim of this study was to investigate the effect of 5-HTP on alveolar bone destruction in periodontitis. Male Sprague-Dawley rats were randomly divided into the following four groups: (1) the control group (without ligature); (2) the 5-HTP group (5-HTP at 25 mg/kg/day without ligature); (3) the L group (ligature+saline placebo); and (4) the L+5-HTP group (ligature+5-HTP at 25 mg/kg/day). Serum serotonin levels were determined by ELISA. The alveolar bones were evaluated with micro-computed tomography and histology. Tartrate-resistant acid phosphatase staining was used to assess osteoclastogenesis. The receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) expression in the periodontium as well as the interleukin-6 positive osteocytes were analysed immunohistochemically. 5-HTP significantly increased serum serotonin levels. In rats with experimental periodontitis, 5-HTP increased alveolar bone resorption and worsened the micro-structural destruction of the alveolar bone. 5-HTP also stimulated osteoclastogenesis and increased RANKL/OPG ratio and the number of IL-6 positive osteocytes. However, 5-HTP treatment alone did not cause alveolar bone loss in healthy rats. The present study showed that 5-HTP aggravated alveolar bone loss, deteriorated alveolar bone micro-structure in the presence of periodontitis, which suggests 5-HTP administration may increase the severity of periodontitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Diabetes mellitus may increase bone loss after occlusal trauma and experimental periodontitis.

    Science.gov (United States)

    de Oliveira Diniz, Claudia K; Corrêa, Mônica G; Casati, Marcio Z; Nociti, Francisco H; Ruiz, Karina G; Bovi Ambrosano, Gláucia Maria; Sallum, Enilson A

    2012-10-01

    Diabetes mellitus (DM) involves metabolic changes that can negatively influence periodontal tissues, resulting in more prevalent and severe periodontitis and impaired bone formation. Occlusal trauma (OT) is an injury of the supportive periodontium that results in bone loss. It can be hypothesized that DM would increase bone loss after OT, mainly when associated with periodontitis. Thus, the aim of the present study is to evaluate the influence of DM on bone response in the furcation area of teeth subjected to OT in the presence, or absence, of experimental periodontitis (EP) in the rat model. Thirty-two male Wistar rats were assigned to four groups: 1) group 1 (G1): DM+OT+EP (n = 8); 2) group 2 (G2): DM+OT (n = 8); 3) group 3 (G3): OT+EP (n = 8); and 4) group 4 (G4): OT (n = 8). G1 and G2 received a single intraperitoneal injection of streptozotocin (STZ). After 10 days, G1 and G3 were subjected to EP by ligature placement. Fifteen days after the start of EP, OT was induced by the creation of a premature contact. The animals were euthanized 35 days after DM induction. DM enhanced bone loss in the presence of OT combined with EP, but did not increase bone loss in teeth subjected to OT alone. EP caused greater bone loss when associated with OT. Within the limits of this animal study, it can be concluded that DM enhances bone loss in the presence of occlusal trauma associated with EP.

  14. New treatment of periodontal diseases by using NF-kappaB decoy oligodeoxynucleotides via prevention of bone resorption and promotion of wound healing.

    Science.gov (United States)

    Shimizu, Hideo; Nakagami, Hironori; Morita, Shosuke; Tsukamoto, Ikuyo; Osako, Mariana Kiomy; Nakagami, Futoshi; Shimosato, Takashi; Minobe, Noriko; Morishita, Ryuichi

    2009-09-01

    Nuclear factor-kappa B (NF-kappaB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-kappaB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-kappaB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-kappaB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-kappaB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-kappaB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-kappaB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-kappaB might be a potential therapy in various bone metabolic diseases.

  15. Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment.

    Science.gov (United States)

    Spirlandeli, Adriano L; Dick-de-Paula, Ingrid; Zamarioli, Ariane; Jorgetti, Vanda; Ramalho, Leandra N Z; Nogueira-Barbosa, Marcello H; Volpon, Jose B; Jordão, Alceu A; Cunha, Fernando Q; Fukada, Sandra Y; de Paula, Francisco J A

    2017-04-01

    The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

  16. Association Between Dietary Fiber Intake and Bone Loss in the Framingham Offspring Study.

    Science.gov (United States)

    Dai, Zhaoli; Zhang, Yuqing; Lu, Na; Felson, David T; Kiel, Douglas P; Sahni, Shivani

    2018-02-01

    Dietary fiber may increase calcium absorption, but its role in bone mineralization is unclear. Furthermore, the health effect of dietary fiber may be different between sexes. We examined the association between dietary fiber (total fiber and fiber from cereal, fruits, vegetables, nuts, and legumes) and bone loss at the femoral neck, trochanter, and lumbar spine (L 2 to L 4 ) in older men and women. In the Framingham Offspring Study, at baseline (1996-2001), diet was assessed using the Willett food-frequency questionnaire, and bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Follow-up BMD was measured in 2001-2005 and 2005-2008 among 792 men (mean age 58.1 years; BMI 28.6 kg/m 2 ) and 1065 women (mean age 57.3 years; BMI 27.2 kg/m 2 ). We used sex-specific generalized estimating equations in multivariable regressions to estimate the difference (β) of annualized BMD change in percent (%ΔBMD) at each skeletal site per 5 g/d increase in dietary fiber. We further estimated the adjusted mean for bone loss (annualized %ΔBMD) among participants in each higher quartile (Q2, Q3, or Q4) compared with those in the lowest quartile (Q1) of fiber intake. Higher dietary total fiber (β = 0.06, p = 0.003) and fruit fiber (β = 0.10, p = 0.008) was protective against bone loss at the femoral neck in men but not in women. When examined in quartiles, men in Q2-Q4 of total fiber had significantly less bone loss at the femoral neck versus those in Q1 (all p fiber from vegetables appeared to be protective against spine bone loss in women but not men. There were no associations with cereal fiber or nut and legume fiber and bone loss in men or women. Our findings suggest that higher dietary fiber may modestly reduce bone loss in men at the hip. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  17. The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation

    DEFF Research Database (Denmark)

    Schaller, Sophie; Henriksen, Kim; Sveigaard, Christina

    2004-01-01

    Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone...... for osteoporosis, daily treatment with 30 mg/kg orally protected bone strength and BMD by approximately 50% 6 weeks after surgery. Most interestingly, bone formation assessed by osteocalcin, mineral apposition rate, and mineralized surface index was not inhibited. MATERIALS AND METHODS: Analysis of chloride......, appearing mainly in osteoclasts, ovaries, appendix, and Purkinje cells. This highly selective distribution predicts that inhibition of ClC-7 should specifically target osteoclasts in vivo. We suggest that NS3736 is inhibiting ClC-7, leading to a bone-specific effect in vivo. RESULTS AND CONCLUSION...

  18. Role of glucocorticoid-induced leucine zipper (GILZ in inflammatory bone loss.

    Directory of Open Access Journals (Sweden)

    Nianlan Yang

    Full Text Available TNF-α plays a key role in the development of rheumatoid arthritis (RA and inflammatory bone loss. Unfortunately, treatment of RA with anti-inflammatory glucocorticoids (GCs also causes bone loss resulting in osteoporosis. Our previous studies showed that overexpression of glucocorticoid-induced leucine zipper (GILZ, a mediator of GC's anti-inflammatory effect, can enhance osteogenic differentiation in vitro and bone acquisition in vivo. To investigate whether GILZ could antagonize TNF-α-induced arthritic inflammation and protect bone in mice, we generated a TNF-α-GILZ double transgenic mouse line (TNF-GILZ Tg by crossbreeding a TNF-α Tg mouse, which ubiquitously expresses human TNF-α, with a GILZ Tg mouse, which expresses mouse GILZ under the control of a 3.6kb rat type I collagen promoter fragment. Results showed that overexpression of GILZ in bone marrow mesenchymal stem/progenitor cells protected mice from TNF-α-induced inflammatory bone loss and improved bone integrity (TNF-GILZ double Tg vs. TNF-αTg, n = 12-15. However, mesenchymal cell lineage restricted GILZ expression had limited effects on TNF-α-induced arthritic inflammation as indicated by clinical scores and serum levels of inflammatory cytokines and chemokines.

  19. Androgen receptors and experimental bone loss - an in vivo and in vitro study.

    Science.gov (United States)

    Steffens, Joao Paulo; Coimbra, Leila Santana; Rossa, Carlos; Kantarci, Alpdogan; Van Dyke, Thomas E; Spolidorio, Luis Carlos

    2015-12-01

    Testosterone is a sex hormone that exhibits many functions beyond reproduction; one such function is the regulation of bone metabolism. The role played by androgen receptors during testosterone-mediated biological processes associated with bone metabolism is largely unknown. This study aims to use a periodontal disease model in vivo in order to assess the involvement of androgen receptors on microbial-induced inflammation and alveolar bone resorption in experimental bone loss. The impact of hormone deprivation was tested through both orchiectomy and chemical blockage of androgen receptor using flutamide (FLU). Additionally, the direct effect of exogenous testosterone, and the role of the androgen receptor, on osteoclastogenesis were investigated. Thirty male adult rats (n=10/group) were subjected to: 1-orchiectomy (OCX); 2-OCX sham surgery; or 3-OCX sham surgery plus FLU, four weeks before the induction of experimental bone loss. Ten OCX sham-operated rats were not subjected to experimental bone loss and served as healthy controls. The rats were euthanized two weeks later, so as to assess bone resorption and the production of inflammatory cytokines in the gingival tissue and serum. In order to study the in vitro impact of testosterone, osteoclasts were differentiated from RAW264.7 cells and testosterone was added at increasing concentrations. Both OCX and FLU increased bone resorption, but OCX alone was observed to increase osteoclast count. IL-1β production was increased only in the gingival tissue of OCX animals, whereas FLU-treated animals presented a decreased expression of IL-6. Testosterone reduced the osteoclast formation in a dose-dependent manner, and significantly impacted the production of TNF-α; FLU partially reversed these actions. When taken together, our results indicate that testosterone modulates experimental bone loss, and that this action is mediated, at least in part, via the androgen receptor. Copyright © 2015 Elsevier Inc. All rights

  20. Use of non-vascularized autologous fibula strut graft in the treatment of segmental bone loss.

    Science.gov (United States)

    Lawal, Y Z; Garba, E S; Ogirima, M O; Dahiru, I L; Maitama, M I; Abubakar, K; Ejagwulu, F S

    2011-01-01

    Fractures resulting in segmental bone loss challenge the orthopedic surgeon. Orthopedic surgeons in developed countries have the option of choosing vascularized bone transfers, bone transport, allogenic bone grafts, bone graft substitutes and several other means to treat such conditions. In developing countries where such facilities or expertise may not be readily available, the surgeon has to rely on other techniques of treatment. Non-vascularized fibula strut graft and cancellous bone grafting provides a reliable means of treating such conditions in developing countries. Over a period of six years all patients with segmental bone loss either from trauma or oncologic resection were included in the study. Data concerning the type of wound, size of gap and skin loss at tumor or fracture were obtained from clinical examination and radiographs. Ten patients satisfied the inclusion criteria for the study. The average length of the fibula strut is 7 cm, the longest being 15 cm and the shortest 3 cm long. The average defect length was 6.5 cm. Five patients had Gustillo III B open tibial fractures. One patient had recurrent giant cell tumor of the distal radius and another had a polyostotic bone cyst of the femur, which was later confirmed to be osteosarcoma. Another had non-union of distal tibial fracture with shortening. One other patient had gunshot injury to the femur and was initially managed by skeletal traction. The tenth patient had a comminuted femoral fracture. All trauma patients had measurement of missing segment, tissue envelope assessment, neurological examination, and debridement under general anesthesia with fracture stabilization with external fixators or casts. Graft incorporation was 80% in all treated patients. Autologous free, non-vascularized fibula and cancellous graft is a useful addition to the armamentarium of orthopedic surgeon in developing countries attempting to manage segmental bone loss, whether created by trauma or excision of tumors.

  1. MicroCT evaluation of bone mineral density loss in human bones

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Liebert P.; Braz, Delson; Lopes, Ricardo T. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE). Lab. de Instrumentacao Nuclear]. E-mails: lnogueira@con.ufrj.br; Barroso, Regina C.; Oliveira, Luis F. [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil). Inst. de Fisica]. E-mail: cely@uerj.br

    2007-07-01

    Bone is a connective tissue largely composed of an organic protein, collagen and the inorganic mineral hydroxyapatite [Ca{sub 10}(PO{sub 4}){sub 6}OH{sub 2}], which combine to provide a mechanical and supportive role in the body. Depending on the orientation of collagen fibers, two types of bone can be distinguished: trabecular and cortical bone. Degree of mineralization is considered an important feature of bone quality. Changes in the degree of mineralization is generally due to osteoporosis, but many recent studies have already shown that alterations in degree of mineralization can occur due to a large variety of factors. The transmission X-ray microtomography is one of the most popular methods, which provides the spatial distribution of the total absorption coefficient inside the sample. The aim of this study was to investigate the suitability of using microCT as a supplementary tool for the diagnosis of the health status of human bones. Eleven samples were constructed simulating the physiological range of bone mineral density (BMD) found in cortical human bone. The samples represent healthy mixtures of swine compact bone dried at room temperature, powdered and mixed with fat (0 - 100 % by mass). The samples were imaged by a microfocus tube (Fein-Focus) with focal size of about 60 {mu}m ({+-}5%), and a CCD camera (0.143 mm pixel size) coupled with an intensifier tube with fluoroscope screen at the Nuclear Instrumentation Laboratory (COPPE/UFRJ), Brazil. The images were reconstructed and treated with suitable software developed at the Nuclear Instrumentation Laboratory. The mineral content in cortical bone is defined by the volume of dry, fat-free bone per unit bulk volume of the bone. The volumes were calculated from the bone density using the relationship between volume and density. The densities of fat and bone were taken to be 0.95 g.cm{sup -3} and 1.92 g.cm{sup -3} respectively. The correlation of the measured absorption coefficient with the mineral content

  2. Reverse total shoulder glenoid baseplate stability with superior glenoid bone loss.

    Science.gov (United States)

    Martin, Elise J; Duquin, Thomas R; Ehrensberger, Mark T

    2017-10-01

    Superior wear of the glenoid bone is common in patients with rotator cuff arthropathy. This can become a treatment challenge for patients who require shoulder arthroplasty. In reverse shoulder arthroplasty (RSA), glenoid bone loss may affect the stability of baseplate fixation. The primary purpose of this biomechanical laboratory study was to assess the initial fixation stability of RSA glenosphere baseplates in the presence of variable amounts of superior glenoid bone loss. High-density solid rigid polyurethane foam (30 pounds/cubic foot) was machined to model the glenoid with variable superior defects that provided different levels of support (100%, 90%, 75%, and 50%) for the glenosphere baseplate. The samples were cyclically loaded (0-750 N at 1 Hz for 5000 cycles) at a 60° glenohumeral angle. The micromotion and migration of the baseplate were calculated from displacement data captured during the loading tests with an array of 3 linear variable differential transformers mounted around the baseplate. Micromotion was significantly greater in samples with 50% defects compared with those with smaller defects. Migration was significantly greater after testing for all defect sizes. Initial fixation of RSA glenosphere baseplates was significantly reduced in models with 50% bone loss on the superior edge compared with models with less bone loss in this high-density bone foam model. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  3. Average annual crestal bone loss of ITI implants following the first year of loading

    Directory of Open Access Journals (Sweden)

    A Hosseinzadeh

    2006-07-01

    Full Text Available BACKGROUND: Long term success of dental implants directly depends on marginal bone resorption. The aim of this study was to determine the annual average bone loss on the mesial and distal aspects of implants following the first year of implantation. METHODS: This was a descriptive analytical study of patients treated with ITI (International Team of Implantology implants at the Dental School of Isfahan University of Medical Sciences from 1998-2002 (1377-81. A total of 15 patients with 41 implants were selected by convenience sampling method. The height of the alveolar bone was measured using panoramic radiography before and after loading with calipers to determine the average bone loss. Other information such as pocket depth, bleeding index, plaque index, gingival recession, was obtained by clinical examinations. The mean bone loss on the mesial & distal sides was analyzed by ANOVA at 0.05 level of significance. RESULTS: The average bone loss on the proximal sides of ITI implants obtained annually after the first year of loading was 0.084 ± 0.035 mm with slight difference on the mesial (0.092 ± 0.035 and distal (0.072 ± 0.033 sides. There was negligible difference between male and female patients. The average survival rate for thirty three months was 95.1%. CONCLUSION: The average bone loss on the mesial and distal sides of ITI implants compared with other studies was satisfactory. Survival and success rates were acceptable. KEYWORDS: Dental implants, bone resorption, survival rate, dental plaque index.

  4. Modeling of Blood Lead Levels in Astronauts Exposed to Lead from Microgravity-Accelerated Bone Loss

    Science.gov (United States)

    Garcia, H.; James, J.; Tsuji, J.

    2014-01-01

    Human exposure to lead has been associated with toxicity to multiple organ systems. Studies of various population groups with relatively low blood lead concentrations (bones, the adverse effects of lead correlate with the concentration of lead in the blood better than with that in the bones. NASA has found that prolonged exposure to microgravity during spaceflight results in a significant loss of bone minerals, the extent of which varies from individual to individual and from bone to bone, but generally averages about 0.5% per month. During such bone loss, lead that had been stored in bones would be released along with calcium. The effects on the concentration of lead in the blood (PbB) of various concentrations of lead in drinking water (PbW) and of lead released from bones due to accelerated osteoporosis in microgravity, as well as changes in exposure to environmental lead before, during, and after spaceflight were evaluated using a physiologically based pharmacokinetic (PBPK) model that incorporated exposure to environmental lead both on earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.

  5. CCR2 elimination in mice results in larger and stronger tibial bones but bone loss is not attenuated following ovariectomy or muscle denervation.

    Science.gov (United States)

    Mader, Tara L; Novotny, Susan A; Lin, Angela S; Guldberg, Robert E; Lowe, Dawn A; Warren, Gordon L

    2014-11-01

    Bone loss due to age and disuse contributes to osteoporosis and increases fracture risk. It has been hypothesized that such bone loss can be attenuated by modulation of the C-C chemokine receptor 2 (CCR2) and/or its ligands. The objectives of this study were to examine the effects of genetic elimination of CCR2 on cortical and trabecular bones in the mouse tibia and how bone loss was impacted following disuse and estrogen loss. Female CCR2 knockout (CCR2(-/-)) and wildtype mice underwent ovariectomy (OVX) or denervation of musculature adjacent to the tibia (DEN) to induce bone loss. Cortical and trabecular structural properties as well as mechanical properties (i.e., strength) of tibial bones were measured. Compared to wildtype mice, CCR2(-/-) mice had tibiae that were up to 9% larger and stronger; these differences could be explained mainly by the 17% greater body mass (P bone loss per se. These findings indicate that while CCR2(-/-) mice do have larger and stronger bones than do wildtype mice, there is minimal evidence that CCR2 elimination provides protection against bone loss during disuse and estrogen loss.

  6. Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice.

    Science.gov (United States)

    Thongchote, Kanogwun; Svasti, Saovaros; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2014-06-15

    A marked decrease in β-globin production led to β-thalassemia, a hereditary anemic disease associated with bone marrow expansion, bone erosion, and osteoporosis. Herein, we aimed to investigate changes in bone mineral density (BMD) and trabecular microstructure in hemizygous β-globin knockout thalassemic (BKO) mice and to determine whether endurance running (60 min/day, 5 days/wk for 12 wk in running wheels) could effectively alleviate bone loss in BKO mice. Both male and female BKO mice (1-2 mo old) showed growth retardation as indicated by smaller body weight and femoral length than their wild-type littermates. A decrease in BMD was more severe in female than in male BKO mice. Bone histomorphometry revealed that BKO mice had decreases in trabecular bone volume, trabecular number, and trabecular thickness, presumably due to suppression of osteoblast-mediated bone formation and activation of osteoclast-mediated bone resorption, the latter of which was consistent with elevated serum levels of osteoclastogenic cytokines IL-1α and -1β. As determined by peripheral quantitative computed tomography, running increased cortical density and thickness in the femoral and tibial diaphyses of BKO mice compared with those of sedentary BKO mice. Several histomorphometric parameters suggested an enhancement of bone formation (e.g., increased mineral apposition rate) and suppression of bone resorption (e.g., decreased osteoclast surface), which led to increases in trabecular bone volume and trabecular thickness in running BKO mice. In conclusion, BKO mice exhibited pervasive osteopenia and impaired bone microstructure, whereas running exercise appeared to be an effective intervention in alleviating bone microstructural defect in β-thalassemia. Copyright © 2014 the American Physiological Society.

  7. Characterization of the bone matrix and its contribution to tooth loss in human cadaveric mandibles.

    Science.gov (United States)

    Matsuura, Takashi; Sasaki, Michiko; Katafuchi, Michitsuna; Tokutomi, Kentaro; Mizumachi, Emiri; Makino, Michiko; Naito, Toru; Sato, Hironobu

    2014-11-01

    It is uncertain as to what extent the major bone matrix constituents, mineral and collagen, show inter-individual variation and dependence on age and sex in jawbones. The purpose of this study was to clarify this uncertainty using cadaveric mandibles and investigate the association of bone matrix with the number of existing teeth. Cortical bone samples (1 × 1 cm) collected from the mental of 48 cadaveric mandibles (27 men and 21 women; age range = 56-93 years and 63-103 years, respectively) were used to quantify three bone matrix indices: mineral content, collagen content and extent of lysine hydroxylation of collagen. Associations with age and comparisons by sex were evaluated based on bone matrix indices and the numbers of existing teeth. The numbers of existing teeth were compared between the groups showing low and high bone matrix index values. A great amount of inter-individual variation was seen in all bone matrix indices. No bone matrix indices were associated with age, while the number of existing teeth was negatively associated with age. The bone matrix indices and number of existing teeth did not differ by sex. The number of existing teeth was nearly twice as high in the group showing high collagen content as in the low collagen group; however, an analysis of covariance showed a significant inter-group difference not from bone matrix indices, but rather from age. Interestingly, in comparison to femoral collagen, mandibular collagen showed lower lysine hydroxylation, which can represent an aspect of bone quality. Mandibular bone matrix shows great inter-individual variation and is independent of age and sex, but did not show as strong a relationship with tooth loss as age. Even so, mandibular collagen may represent a unique characteristic of bone matrix and deserves to be further investigated.

  8. Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis.

    Science.gov (United States)

    Wang, Guixin; Wang, Jia; Sun, Dawei; Xin, Jingyi; Wang, Liping; Huang, Dong; Wu, Weichi; Xian, Cory J

    2016-08-23

    BACKGROUND Although it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown. MATERIAL AND METHODS The current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures. RESULTS While the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin. CONCLUSIONS Our results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss.

  9. Marginal bone loss around tilted implants in comparison to straight implants: a meta-analysis.

    Science.gov (United States)

    Monje, Alberto; Chan, Hsun-Liang; Suarez, Fernando; Galindo-Moreno, Pablo; Wang, Hom-Lay

    2012-01-01

    The primary aim of this systematic review was to compare the amount of marginal bone loss around tilted and straight implants. As the secondary aim, the incidence of biomechanic complications was compared. An electronic literature search from five databases, for the years 2000 to 2011, and a hand search in implant-related journals were conducted. Clinical human studies in the English language that had reported marginal bone loss in tilted and straight implants at 12-months follow-up or longer were included. Mean marginal bone loss and the number of implants that were available for analysis were extracted from original articles for meta-analyses. Eight (six prospective and two retrospective) studies were included. One-year data were available in seven articles, which included 1,015 (451 tilted) implants. Three articles provided 3- to 5-year data from 302 (164 tilted) implants. No significant difference in weighted mean marginal bone loss was found between the tilted and straight implants in the short and medium terms. Three articles reported the incidence of biomechanic complications. There was not enough information to make a comparison. This meta-analysis failed to support the hypothesis that tilted implants that were splinted for the support of fixed prostheses had more marginal bone loss. Additionally, there was not enough evidence to claim a higher incidence of biomechanic complications in tilted implants. However, due to the nature of the study design of the included articles, caution should be exercised when interpreting the results of this review.

  10. Arthritis-induced alveolar bone loss is associated with changes in the composition of oral microbiota.

    Science.gov (United States)

    Corrêa, Jôice Dias; Saraiva, Adriana Machado; Queiroz-Junior, Celso Martins; Madeira, Mila Fernandes Moreira; Duarte, Poliana Mendes; Teixeira, Mauro Martins; Souza, Danielle Glória; da Silva, Tarcília Aparecida

    2016-06-01

    Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory disorders that cause bone loss. PD tends to be more prevalent and severe in RA patients. Previous experimental studies demonstrated that RA triggers alveolar bone loss similarly to PD. The aim of this study was to investigate if arthritis-induced alveolar bone loss is associated with modification in the oral microbiota. Checkerboard DNA-DNA hybridization was employed to analyze forty oral bacterial species in 3 groups of C57BL/6 mice: control (n = 12; without any challenge); Y4 (n = 8; received oral inoculation of Aggregatibacter Actinomycetemcomitans strain FDC Y4) and AIA group (n = 12; chronic antigen-induced arthritis). The results showed that AIA and Y4 group exhibited similar patterns of bone loss. The AIA group exhibited higher counts of most bacterial species analyzed with predominance of Gram-negative species similarly to infection-induced PD. Prevotella nigrescens and Treponema denticola were detected only in the Y4 group whereas Campylobacter showae, Streptococcus mitis and Streptococcus oralis were only found in the AIA group. Counts of Parvimonas micra, Selenomonas Noxia and Veillonella parvula were greater in the AIA group whereas Actinomyces viscosus and Neisseira mucosa were in large proportion in Y4 group. In conclusion, AIA is associated with changes in the composition of the oral microbiota, which might account for the alveolar bone loss observed in AIA mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss

    Science.gov (United States)

    Zhang, Xiangming; Wang, Ping; Wang, Ya

    2015-11-01

    Bone density loss in astronauts on long-term space missions is a chief medical concern. Microgravity in space is the major cause of bone density loss (osteopenia), and it is believed that high linear energy transfer (LET) radiation in space exacerbates microgravity-induced bone density loss; however, the mechanism remains unclear. It is known that acidic serine- and aspartate-rich motif (ASARM) as a small peptide released by matrix extracellular phosphoglycoprotein (MEPE) promotes osteopenia. We previously discovered that MEPE interacted with checkpoint kinase 1 (CHK1) to protect CHK1 from ionizing radiation promoted degradation. In this study, we addressed whether the CHK1-MEPE pathway activated by radiation contributes to the effects of microgravity on bone density loss. We examined the CHK1, MEPE and secreted MEPE/ASARM levels in irradiated (1 Gy of X-ray) and rotated cultured human osteoblast cells. The results showed that radiation activated CHK1, decreased the levels of CHK1 and MEPE in human osteoblast cells and increased the release of MEPE/ASARM. These results suggest that the radiation-activated CHK1/MEPE pathway exacerbates the effects of microgravity on bone density loss, which may provide a novel targeting factor/pathway for a future countermeasure design that could contribute to reducing osteopenia in astronauts.

  12. The Effect of Calendula officinalis on Oxidative Stress and Bone Loss in Experimental Periodontitis

    Directory of Open Access Journals (Sweden)

    Mariana dos Reis Lima

    2017-06-01

    Full Text Available Periodontitis is associated with reduced antioxidant capacity and increased oxidative damage. Oxidative stress induces inflammation and bone loss contributing to the pathological progression of periodontal disease. Calendula officinalis (CLO has demonstrated anti-inflammatory and anti-oxidant activities. Therefore, the aim of this study was to evaluate the effect of CLO on oxidative stress and bone loss in rats subjected to experimental periodontitis (EP. For this, 72 male Wistar rats were divided into groups: Naïve, Saline (SAL and CLO. Rats received SAL or CLO (90 mg/kg 30 min before ligature and daily until the 11th day. Naïve group experienced no manipulation. After 11 days, the animals were euthanized and left maxillae collected for macroscopic analysis of alveolar bone loss (ABL. Periodontium was analyzed by macroscopy, scanning electron microscopy; confocal and light polarized microscopy. Immunohistochemical examination of DKK1, WNT 10b and β-catenin was performed. The gingival tissue was collected to reduced glutathione (GSH, superoxide dismutase (SOD, catalase (CAT and malondialdehyde (MDA analyses. The 11 days of ligature induced bone loss, breakdown of collagen fibers, increased the immunostaining DKK-1 while reduced WNT 10b and β-catenin expressions. Periodontitis reduced GSH, SOD, CAT and increase MDA. All findings were reversed by 90 mg/kg of CLO. In summary our findings demonstrated that CLO reduced oxidative stress and bone loss and preserved collagen fibers in rats with EP, with participation of WNT signaling pathway.

  13. The Effect of Calendula officinalis on Oxidative Stress and Bone Loss in Experimental Periodontitis

    Science.gov (United States)

    Lima, Mariana dos Reis; Lopes, Amanda P.; Martins, Conceição; Brito, Gerly A. C.; Carneiro, Virgínia C.; Goes, Paula

    2017-01-01

    Periodontitis is associated with reduced antioxidant capacity and increased oxidative damage. Oxidative stress induces inflammation and bone loss contributing to the pathological progression of periodontal disease. Calendula officinalis (CLO) has demonstrated anti-inflammatory and anti-oxidant activities. Therefore, the aim of this study was to evaluate the effect of CLO on oxidative stress and bone loss in rats subjected to experimental periodontitis (EP). For this, 72 male Wistar rats were divided into groups: Naïve, Saline (SAL) and CLO. Rats received SAL or CLO (90 mg/kg) 30 min before ligature and daily until the 11th day. Naïve group experienced no manipulation. After 11 days, the animals were euthanized and left maxillae collected for macroscopic analysis of alveolar bone loss (ABL). Periodontium was analyzed by macroscopy, scanning electron microscopy; confocal and light polarized microscopy. Immunohistochemical examination of DKK1, WNT 10b and β-catenin was performed. The gingival tissue was collected to reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) analyses. The 11 days of ligature induced bone loss, breakdown of collagen fibers, increased the immunostaining DKK-1 while reduced WNT 10b and β-catenin expressions. Periodontitis reduced GSH, SOD, CAT and increase MDA. All findings were reversed by 90 mg/kg of CLO. In summary our findings demonstrated that CLO reduced oxidative stress and bone loss and preserved collagen fibers in rats with EP, with participation of WNT signaling pathway. PMID:28701962

  14. The Effect ofCalendula officinalison Oxidative Stress and Bone Loss in Experimental Periodontitis.

    Science.gov (United States)

    Lima, Mariana Dos Reis; Lopes, Amanda P; Martins, Conceição; Brito, Gerly A C; Carneiro, Virgínia C; Goes, Paula

    2017-01-01

    Periodontitis is associated with reduced antioxidant capacity and increased oxidative damage. Oxidative stress induces inflammation and bone loss contributing to the pathological progression of periodontal disease. Calendula officinalis (CLO) has demonstrated anti-inflammatory and anti-oxidant activities. Therefore, the aim of this study was to evaluate the effect of CLO on oxidative stress and bone loss in rats subjected to experimental periodontitis (EP). For this, 72 male Wistar rats were divided into groups: Naïve, Saline (SAL) and CLO. Rats received SAL or CLO (90 mg/kg) 30 min before ligature and daily until the 11th day. Naïve group experienced no manipulation. After 11 days, the animals were euthanized and left maxillae collected for macroscopic analysis of alveolar bone loss (ABL). Periodontium was analyzed by macroscopy, scanning electron microscopy; confocal and light polarized microscopy. Immunohistochemical examination of DKK1, WNT 10b and β-catenin was performed. The gingival tissue was collected to reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) analyses. The 11 days of ligature induced bone loss, breakdown of collagen fibers, increased the immunostaining DKK-1 while reduced WNT 10b and β-catenin expressions. Periodontitis reduced GSH, SOD, CAT and increase MDA. All findings were reversed by 90 mg/kg of CLO. In summary our findings demonstrated that CLO reduced oxidative stress and bone loss and preserved collagen fibers in rats with EP, with participation of WNT signaling pathway.

  15. Recurrent anterior glenohumeral instability: the quantification of glenoid bone loss using magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Martins e Souza, Patricia [Fleury Medicina e Saude and Instituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, RJ (Brazil); Brandao, Bruno Lobo; Motta, Geraldo; Monteiro, Martim [Instituto Nacional de Traumatologia e Ortopedia, Rio de Janeiro, RJ (Brazil); Brown, Eduardo [Grupo Fleury Medicina Diagnostica, Rio de Janeiro, RJ (Brazil); Marchiori, Edson [Universidade Federal do Rio de Janeiro, Petropolis, RJ (Brazil)

    2014-08-15

    To investigate the accuracy of conventional magnetic resonance imaging (MRI) in determining the severity of glenoid bone loss in patients with anterior shoulder dislocation by comparing the results with arthroscopic measurements. Institutional review board approval and written consent from all patients were obtained. Thirty-six consecutive patients (29 men, seven women; mean age, 34.5 [range, 18-55] years) with recurrent anterior shoulder dislocation (≥3 dislocations; mean, 37.9; range, 3-200) and suspected glenoid bone loss underwent shoulder MRI before arthroscopy (mean interval, 28.5 [range, 9-73] days). Assessments of glenoid bone loss by MRI (using the best-fit circle area method) and arthroscopy were compared. Inter- and intrareader reproducibility of MRI-derived measurements was evaluated using arthroscopy as a comparative standard. Glenoid bone loss was evident on MRI and during arthroscopy in all patients. Inter- and intrareader correlations of MRI-derived measurements were excellent (intraclass correlation coefficient = 0.80-0.82; r = 0.81-0.86). The first and second observers' measurements showed strong (r = 0.76) and moderate (r = 0.69) interreader correlation, respectively, with arthroscopic measurements. Conventional MRI can be used to measure glenoid bone loss, particularly when employed by an experienced musculoskeletal radiologist. (orig.)

  16. Fusobacterium nucleatum and Tannerella forsythia Induce Synergistic Alveolar Bone Loss in a Mouse Periodontitis Model

    Science.gov (United States)

    Settem, Rajendra P.; El-Hassan, Ahmed Taher; Honma, Kiyonobu; Stafford, Graham P.

    2012-01-01

    Tannerella forsythia is strongly associated with chronic periodontitis, an inflammatory disease of the tooth-supporting tissues, leading to tooth loss. Fusobacterium nucleatum, an opportunistic pathogen, is thought to promote dental plaque formation by serving as a bridge bacterium between early- and late-colonizing species of the oral cavity. Previous studies have shown that F. nucleatum species synergize with T. forsythia during biofilm formation and pathogenesis. In the present study, we showed that coinfection of F. nucleatum and T. forsythia is more potent than infection with either species alone in inducing NF-κB activity and proinflammatory cytokine secretion in monocytic cells and primary murine macrophages. Moreover, in a murine model of periodontitis, mixed infection with the two species induces synergistic alveolar bone loss, characterized by bone loss which is greater than the additive alveolar bone losses induced by each species alone. Further, in comparison to the single-species infection, mixed infection caused significantly increased inflammatory cell infiltration in the gingivae and osteoclastic activity in the jaw bones. These data show that F. nucleatum subspecies and T. forsythia synergistically stimulate the host immune response and induce alveolar bone loss in a murine experimental periodontitis model. PMID:22547549

  17. Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and their Implications for Bone Strain

    Science.gov (United States)

    Peterman, M.; McCrory, J. L.; Sharkey, N. A.; Piazza, S.; Cavanagh, P. R.

    1999-01-01

    Effective countermeasures to prevent loss of bone mineral during long duration space flight remain elusive. Despite an exercise program on MIR flights, the data from LeBlanc et al. (1996) indicated that there was still a mean rate of loss of bone mineral density in the proximal femur of 1.58% per month (n=18, flight duration 4 - 14.4 months). The specific mechanisms regulating bone mass are not known, but most investigators agree that bone maintenance is largely dependent upon mechanical demand and the resultant local bone strains. A plausible hypothesis is that bone loss during space flight, such as that reported by LeBlanc et al. (1996), may result from failure to effectively load the skeleton in order to generate localized bone strains of sufficient magnitude to prevent disuse osteoporosis. A variety of methods have been proposed to simulate locomotor exercise in reduced gravity. In such simulations, and in an actual microgravity environment, a gravity replacement load (GRL) must always be added to return the exercising subject to the support surface and the resulting skeletal load is critically dependent upon the magnitude of the GRL. To our knowledge, GRLs during orbital flight have only been measured once (on STS 81) and it is likely that most or all prior treadmill exercise in space has used GRLs that were less than one body weight. McCrory (1997) has shown that subjects walking and running in simulated zero-G can tolerate GRLs of 1 if an appropriate harness is used. Several investigators have attempted to measure in vivo strains and forces in the bones of humans, but have faced ethical and technical limitations. The anteromedial aspect of the tibial midshaft has been a common site for the placement of strain gauges; one reason to measure strains in the anterior tibia is that this region is surgically accessible. Aamodt et al. (1997) were able to measure strains on the lateral surface of the proximal femur only because their experimental subjects were

  18. CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity.

    Science.gov (United States)

    Li, Yuheng; Zhong, Guohui; Sun, Weijia; Zhao, Chengyang; Zhang, Pengfei; Song, Jinping; Zhao, Dingsheng; Jin, Xiaoyan; Li, Qi; Ling, Shukuan; Li, Yingxian

    2015-11-04

    The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity.

  19. Simulation analysis for effects of bone loss on acceleration tolerance of human lumbar vertebra

    Science.gov (United States)

    Ma, Honglei; Zhang, Feng; Zhu, Yu; Xiao, Yanhua; Wazir, Abrar

    2014-02-01

    The purpose of the present study was to analyze and predict the changes in acceleration tolerance of human vertebra as a result of bone loss caused by long-term space flight. A human L3-L4 vertebra FEM model was constructed, in which the cancellous bone was separated, and surrounding ligaments were also taken into account. The simulation results demonstrated that bone loss has more of an effect on the acceleration tolerance in x-direction. The results serve to aid in the creation of new acceleration tolerance standards, ensuring astronauts return home safely after long-term space flight. This study shows that more attention should be focused on the bone degradation of crew members and to create new protective designs for space capsules in the future.

  20. Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo

    Directory of Open Access Journals (Sweden)

    Yun-Ho Hwang

    2018-03-01

    Full Text Available Osteoporosis is characterized by a reduction of the bone mineral density (BMD and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we examined the antiosteoporotic effect of AST on bone mass in ovariectomized (OVX mice and its possible mechanism of action. The administration of AST (5, 10 mg/kg for 6 weeks suppressed the enhancement of serum calcium, inorganic phosphorus, alkaline phosphatase, total cholesterol, and tartrate-resistant acid phosphatase (TRAP activity. The bone mineral density (BMD and bone microarchitecture of the trabecular bone in the tibia and femur were recovered by AST exposure. Moreover, in the in vitro experiment, we demonstrated that AST inhibits osteoclast formation through the expression of the nuclear factor of activated T cells (NFAT c1, dendritic cell-specific transmembrane protein (DC-STAMP, TRAP, and cathepsin K without any cytotoxic effects on bone marrow-derived macrophages (BMMs. Therefore, we suggest that AST may have therapeutic potential for the treatment of postmenopausal osteoporosis.

  1. Computational Analysis of Artificial Gravity as a Possible Countermeasure to Spaceflight Induced Bone Loss

    Science.gov (United States)

    Mulugeta, L.; Werner, C. R.; Pennline, J. A.

    2015-01-01

    During exploration class missions, such as to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Data has shown that astronauts lose bone mass at a rate of 1% to 2% a month in microgravity, particularly in lower extremities such as the proximal femur. Exercise countermeasures have not completely eliminated bone loss from long duration spaceflight missions, which leaves astronauts susceptible to early onset osteoporosis and greater risk of fracture. Introduction of the Advanced Resistive Exercise Device and other large exercise devices on the International Space Station (ISS), coupled with improved nutrition, has further minimized bone loss. However, unlike the ISS, exploration vehicles will have very limited volume and power available to accommodate such capabilities. Therefore, novel concepts like artificial gravity systems are being explored as a means to provide sufficient load stimulus to the musculoskeletal system to mitigate bone changes that may lead to early onset osteoporosis and increased risk of fracture. Currently, there is minimal data available to drive further research and development efforts to appropriately explore such options. Computational modeling can be leveraged to gain insight on the level of osteoprotection that may be achieved using artificial gravity produced by a spinning spacecraft or centrifuge. With this in mind, NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone both for gravitational unloading condition and the equivalent of 1g daily load stimulus. Using this model, it is possible to simulate vBMD changes in trabecular and cortical bone under different gravity conditions. In this presentation, we will discuss our preliminary findings regarding if and how artificial gravity may be used to mitigate spaceflight induced bone loss.

  2. Recurrent Anterior Shoulder Instability With Combined Bone Loss: Treatment and Results With the Modified Latarjet Procedure.

    Science.gov (United States)

    Yang, Justin S; Mazzocca, Augustus D; Cote, Mark P; Edgar, Cory M; Arciero, Robert A

    2016-04-01

    Recurrent anterior glenohumeral dislocation in the setting of an engaging Hill-Sachs lesion is high. The Latarjet procedure has been well described for restoring glenohumeral stability in patients with >25% glenoid bone loss. However, the treatment for patients with combined humeral head and mild (Latarjet for patients with combined humeral and glenoid defects and compares the results for patients with ≤25% glenoid bone loss versus patients with >25% glenoid bone loss. The hypothesis was that the 2 groups would have equivalent subjective outcomes and recurrence rates. Cohort Study; Level of evidence, 3. Modified Latarjet was performed in 40 patients with recurrent anterior shoulder instability, engaging Hill-Sachs by examination confirmed with arthroscopy, and ≤25% anterior glenoid bone loss (group A). A second group of 12 patients were identified to have >25% glenoid bone loss with an engaging Hill-Sachs lesion (group B). The mean follow-up time was 3.5 years. All patients were assessed for their risk of recurrence using the Instability Severity Index score and Beighton score and had preoperative 3-dimensional imaging to assess humeral and glenoid bone loss. Single Assessment Numeric Evaluation (SANE), Western Ontario Shoulder Instability Index (WOSI), recurrence rate, radiographs, range of motion, and dynamometer strength were used to assess outcomes. A multivariate analysis was performed. Glenoid bone loss averaged 15% in group A compared with 34% in group B. Both groups had comparable WOSI scores (356 vs 475; P = .311). In multivariate analysis, the number of previous surgeries and Beighton score were directly correlated with WOSI score in Latarjet patients. The SANE score was better in group A (86 vs 77; P = .02). Group B experienced more loss of external rotation (9.2° vs 15.8°; P = .0001) and weaker thumbs-down abduction and external rotation strength (P .999) were similar for both groups. The complication rate was 25% for both groups. The modified

  3. Bone mineral content and bone metabolism in young adults with severe periodontitis

    DEFF Research Database (Denmark)

    Wowern von, N.; Westergaard, J.; Kollerup, G.

    2001-01-01

    Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis......Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis...

  4. Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss

    Science.gov (United States)

    Spector, Elisabeth; LeBlanc, A.; Sibonga, J.; Matsumoto, T.; Jones, J.; Smith, S. M.; Shackelford, L.; Shapiro, J.; Lang, T.; Evans, H.; hide

    2009-01-01

    The purpose of this research is to determine whether anti-resorptive pharmaceuticals such as bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density and bone strength and the increased renal stone risk documented on previous long-duration space flights [1-3]. Losses averaged 1 to 2 percent per month in such regions as the lumbar spine and hip. Although losses showed significant heterogeneity among individuals and between bones within a given subject, space flight-induced bone loss was a consistent finding. More than 90 percent of astronauts and cosmonauts on long-duration flights (average 171 days) aboard Mir and the ISS, had a minimum 5 percent loss in at least one skeletal site, 40 percent of them had a 10 percent or greater loss in at least one skeletal site, and 22 percent of the Mir cosmonauts experienced a 15 to 20 percent loss in at least one site. These losses occurred even though the crewmembers performed time-consuming in-flight exercise regimens. Moreover, a recent study of 16 ISS astronauts using quantitative computed tomography (QCT) demonstrated trabecular bone losses from the hip averaging 2.3 percent per month [4]. These losses were accompanied by significant losses in hip bone strength that may not be recovered quickly [5]. This rapid loss of bone mass results from a combination of increased and uncoupled remodeling, as demonstrated by increased resorption with little or no change in bone formation markers [6-7]. This elevated remodeling rate likely affects the cortical and trabecular architecture and may lead to irreversible changes. In addition to bone loss, the resulting hypercalciuria increases renal stone risk. Therefore, it is logical to attempt to attenuate this increased remodeling with anti-resorption drugs such as bisphosphonates. Success with alendronate was demonstrated in a bed rest study [8]. This work has been extended to space

  5. Mandibular atrophy and metabolic bone loss. Mandibular ridge augmentation by combined sandwich-visor osteotomy and resorption related to metabolic bone state

    NARCIS (Netherlands)

    Bras, J.; van Ooij, C. P.; van den Akker, H. P.

    1985-01-01

    22 edentulous women, 11 with and 11 without signs of metabolic bone loss were treated by a combined sandwich-visor osteotomy. Longitudinal studies showed a higher rate of resorption in women with radiographic signs of metabolic bone loss. The analysis was based upon lateral cephalometry

  6. Mandibular atrophy and metabolic bone loss. Mandibular ridge augmentation by combined sandwich-visor osteotomy and resorption related to metabolic bone state. A 5-year follow-up

    NARCIS (Netherlands)

    Habets, L. L.; Bras, J.; van den Akker, H. P.; Borgmeyer-Hoelen, A. M.; van Ooij, C. P.

    1987-01-01

    92 patients, 31 with and 61 without signs of metabolic bone loss, were treated with a combined sandwich-visor osteotomy. A 5-year follow-up showed a significantly higher rate of resorption in patients with radiographic signs of metabolic bone loss. The analysis was based upon lateral cephalometry

  7. Mucosal inflammation and incidence of crestal bone loss among implant patients: a 10-year study.

    Science.gov (United States)

    Cecchinato, Denis; Parpaiola, Andrea; Lindhe, Jan

    2014-07-01

    The objective of this prospective study was to determine the prevalence and incidence of marginal bone loss and, in addition, peri-implantitis in subjects and implant sites after 10 years in function. One hundred and thirty-three subjects with a total of 407 implants that had been in function for about 5 years attended a follow-up visit in 2007 (visit 2; V2). 100 of the 133 subjects returned for a new clinical and radiographic examination in 2012 (visit 3; V3). The clinical examination included assessment of "bleeding on probing" (BoP+) and "probing pocket depth." Subjects with implant sites that in the radiograph exhibited crater-shaped marginal bone loss of >0.5 mm were identified as losers. During the interval between V2 and V3 (about 5 years), 13 implants in 7 subjects exhibited progressive bone loss and were removed. The overall amount of crestal bone loss that had occurred at the remaining implants between visit 1 (V1; ≥1 year of loading) and V3 (10 years) was small (0.36 ± 1.4 mm). The bone-level reduction was twice as great between V2 and V3 as between V1 and V2. Forty subjects and 75 (26%) implant sites exhibited marginal bone loss of >0.5 mm between V1 and V3. In the interval between V2 and V3, 37 new implant sites lost significant amounts of bone. During the entire 10-year period (V1-V3), 12% of patients and 5% of implants displayed signs of peri-implantitis (bone loss >0.5 mm, BoP+, PPD ≥6 mm), while in the V2-V3 interval, the corresponding numbers were 10% (patients) and 4% (implant sites). Sites with marginal bone loss of ≥1 mm were not common among implant patients. Peri-implantitis occurred in about 10% of patients and 4% of implant sites. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Use of 3D MR reconstructions in the evaluation of glenoid bone loss: a clinical study

    International Nuclear Information System (INIS)

    Gyftopoulos, Soterios; Beltran, Luis S.; Yemin, Avner; Recht, Michael P.; Strauss, Eric; Meislin, Robert; Jazrawi, Laith

    2014-01-01

    To assess the ability of 3D MR shoulder reconstructions to accurately quantify glenoid bone loss in the clinical setting using findings at the time of arthroscopy as the gold standard. Retrospective review of patients with MR shoulder studies that included 3D MR reconstructions (3D MR) produced using an axial Dixon 3D-T1W-FLASH sequence at our institution was conducted with the following inclusion criteria: history of anterior shoulder dislocation, arthroscopy (OR) performed within 6 months of the MRI, and an estimate of glenoid bone loss made in the OR using the bare-spot method. Two musculoskeletal radiologists produced estimates of bone loss along the glenoid width, measured in mm and %, on 3D MR using the best-fit circle method, which were then compared to the OR measurements. There were a total of 15 patients (13 men, two women; mean age, 28, range, 19-51 years). There was no significant difference, on average, between the MRI (mean 3.4 mm/12.6 %; range, 0-30 %) and OR (mean, 12.7 %; range, 0-30 %) measurements of glenoid bone loss (p = 0.767). A 95 % confidence interval for the mean absolute error extended from 0.45-2.21 %, implying that, when averaged over all patients, the true mean absolute error of the MRI measurements relative to the OR measurements is expected to be less than 2.21 %. Inter-reader agreement between the two readers had an IC of 0.92 and CC of 0.90 in terms of percentage of bone loss. 3D MR reconstructions of the shoulder can be used to accurately measure glenoid bone loss. (orig.)

  9. Comparison between inverted and unprocessed digitized radiographic imaging in periodontal bone loss measurements

    Directory of Open Access Journals (Sweden)

    Gulnara Scaf

    2007-12-01

    Full Text Available The advances in digital imaging technology in dentistry have provided an alternative to film-based radiography and have given new options to detect periodontal bone loss. The purpose of this study was to compare inverted and unprocessed digitized radiographic imaging in periodontal bone loss measurements. Thirty-five film-based periapical radiographs of patients suffering from moderate to advanced untreated periodontal bone loss associated to lower premolar and molars was selected from the department files, with 40 bone loss areas. The film-based radiographs were digitized with a flatbed scanner with a transparency and radiograph adapter used for transilluminating the radiograph imaging. Digitization was performed at 600 dpi and in gray scale. The images were digitized using Image Tool software by applying image inversion, that is, transformation of radiopaque structures into radiolucent structures and vice-versa. The digital data were saved as JPEG files. The images were displayed on a 15-inch and 24-bit video monitor under reduced room lighting. One calibrated examiner performed all radiographic measurements, three times, from the cementoenamel junction to the most apical extension of the bone loss, in both types of image (inverted and unprocessed. Brightness and contrast were adjusted according to the examiner's individual demand. Intraclass correlation coefficient was used to compare the measurements from both types of images. The means of radiographic measurements, in mm, for inverted and unprocessed digitized imaging were 6.4485 and 6.3790, respectively. The intraclass correlation coefficient was significant (0.99 The inverted and unprocessed digitized radiographic images were reliable and there was no difference in the diagnostic accuracy between these images regarding periodontal bone loss measurements.

  10. A cross-sectional study on the prevalence of marginal bone loss among implant patients.

    Science.gov (United States)

    Cecchinato, Denis; Parpaiola, Andrea; Lindhe, Jan

    2013-01-01

    The aim of the present cross-sectional retrospective study was to determine bone loss in a sample of subjects restored with implant-supported prostheses and the prevalence and severity of peri-implantitis in a sub-sample. A total of 139 patients who had attended a follow-up visit in 2007 were considered for inclusion. Subjects with implants that had been in function for less than 3 years or had poor quality radiographs were excluded. The final study population comprised 133 subjects with a total of 407 implants. Radiographic measurements identified subjects who had ≥1 implant site exhibiting marginal bone loss of >0.5 mm; 40 subjects met this criterion and were recalled for a clinical examination. Of the 40 subjects that were recalled for the clinical examination, 30 attended. The following parameters were recorded at mesial, distal, buccal, and lingual/palatal aspects of all implants: oral hygiene standard (plaque), bleeding on probing, probing pocket depth (PPD). The mean interval between the baseline (1-year post-loading) and the follow-up radiographs was 4.8 ± 2.3 years. In the total subject sample (133 subjects and 407 implants), the mean amount of marginal bone loss that had occurred was 0.2 ± 1.2 mm. Ninety-three subjects with 246 implant sites exhibited no bone level alteration (group A), whereas 40 subjects with 161 implant sites (group B) displayed marginal bone loss of >0.5 mm at ≥1 implant (loser site). Sixty-eight implant sites in group B exhibited bone loss of >0.5 mm. However, only 20% of subjects and 11% of sites had lost >1 mm marginal bone, and 8% of subjects and 4% of sites had lost >2 mm bone. The total amount of bone loss that had occurred in group B was (i) 0.88 ± 1.5 mm and (ii) among the loser sites 2.1 ± 1.4 mm. Thirty subjects from group B were exposed to a clinical examination; out of 37 sites with bone loss >0.5 mm in this subgroup, 29 sites had a PPD value of ≥4 mm. Marginal bone loss (>0.5 mm) at implants

  11. Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss.

    Science.gov (United States)

    Raynaud-Messina, Brigitte; Bracq, Lucie; Dupont, Maeva; Souriant, Shanti; Usmani, Shariq M; Proag, Amsha; Pingris, Karine; Soldan, Vanessa; Thibault, Christophe; Capilla, Florence; Al Saati, Talal; Gennero, Isabelle; Jurdic, Pierre; Jolicoeur, Paul; Davignon, Jean-Luc; Mempel, Thorsten R; Benichou, Serge; Maridonneau-Parini, Isabelle; Vérollet, Christel

    2018-03-13

    Bone deficits are frequent in HIV-1-infected patients. We report here that osteoclasts, the cells specialized in bone resorption, are infected by HIV-1 in vivo in humanized mice and ex vivo in human joint biopsies. In vitro, infection of human osteoclasts occurs at different stages of osteoclastogenesis via cell-free viruses and, more efficiently, by transfer from infected T cells. HIV-1 infection markedly enhances adhesion and osteolytic activity of human osteoclasts by modifying the structure and function of the sealing zone, the osteoclast-specific bone degradation machinery. Indeed, the sealing zone is broader due to F-actin enrichment of its basal units (i.e., the podosomes). The viral protein Nef is involved in all HIV-1-induced effects partly through the activation of Src, a regulator of podosomes and of their assembly as a sealing zone. Supporting these results, Nef-transgenic mice exhibit an increased osteoclast density and bone defects, and osteoclasts derived from these animals display high osteolytic activity. Altogether, our study evidences osteoclasts as host cells for HIV-1 and their pathological contribution to bone disorders induced by this virus, in part via Nef.

  12. Changes in bone marrow lesions in response to weight-loss in obese knee osteoarthritis patients

    DEFF Research Database (Denmark)

    Gudbergsen, Henrik; Boesen, Mikael; Christensen, Robin

    2013-01-01

    are related to the future degeneration of the knee joint as well as prevalent clinical symptoms. The aim of this study was to investigate the changes in BMLs after a 16-week weight-loss period in obese subjects with KOA and relate changes in BMLs to the effects of weight-loss on clinical symptoms.......Patients are susceptible for knee osteoarthritis (KOA) with increasing age and obesity and KOA is expected to become a major disabling disease in the future. An important feature of KOA on magnetic resonance imaging (MRI) is changes in the subchondral bone, bone marrow lesions (BMLs), which...

  13. Antibody-based inhibition of circulating DLK1 protects from estrogen deficiency-induced bone loss in mice

    DEFF Research Database (Denmark)

    Figeac, Florence; Andersen, Ditte C.; Nipper Nielsen, Casper A.

    2018-01-01

    /TV) and inhibition of bone resorption. No significant changes were observed in total fat mass or in the number of bone marrow adipocytes. These results support the potential use of anti-DLK1 antibody therapy as a novel intervention to protect from E deficiency associated bone loss....... deficiency-associated bone loss in mice. Thus, we generated mouse monoclonal anti-mouse DLK1 antibodies (MAb DLK1) that enabled us to reduce and also quantitate the levels of bioavailable serum DLK1 in vivo. Ovariectomized (ovx) mice were injected intraperitoneally twice weekly with MAb DLK1 over a period...... of one month. DEXA-, microCT scanning, and bone histomorphometric analyses were performed. Compared to controls, MAb DLK1 treated ovx mice were protected against ovx-induced bone loss, as revealed by significantly increased total bone mass (BMD) due to increased trabecular bone volume fraction (BV...

  14. Endogenous opioids regulate alveolar bone loss in a periodontal disease model.

    Science.gov (United States)

    Queiroz-Junior, Celso M; Maltos, Kátia L M; Pacheco, Daniela F; Silva, Tarcília Aparecida; Albergaria, Juliano D S; Pacheco, Cinthia M F

    2013-10-06

    The anti-inflammatory effects of exogenous opioid compounds have been demonstrated in several conditions. Nevertheless, the function of endogenous opioid peptides released by the host during inflammatory processes deserves further characterization. The aim of this study was to verify whether endogenous opioids are involved in the progression of the inflammatory alveolar bone loss induced by ligature in rats. The experimental model of periodontal disease (PD) induced by ligature in rats was used throughout the study. A silk ligature was placed around the 2nd upper molar of male Holtzman rats, for 7 days. Rats received different doses of either the non-selective opioid antagonist naloxone or vehicle, locally into the afflicted gingival tissue, from the 3rd to the 5th day after ligature placement. In the 7th experimental day, rats were euthanized and their maxillae were collected for evaluation of alveolar bone and fiber attachment loss, presence of neutrophils (myeloperoxidase assay), osteoclast amount, and levels of cytokines IL-6, TNF-α, IL-8 and IL-10 in periodontal tissues. Naloxone increased alveolar bone loss significantly, in a dose-dependent manner, in relation to vehicle-treated rats. In contrast, the opioid antagonist did not affect the loss of fiber attachment. The treatment with naloxone also induced a significant increase in myeloperoxidase levels, osteoclast number and cytokines in periodontal tissues of rats with ligature-induced PD. Endogenous opioids protect the host from the progression of inflammatory alveolar bone loss that occurs in chronic periodontitis. © 2013.

  15. Interventions to prevent occupational noise-induced hearing loss.

    Science.gov (United States)

    Tikka, Christina; Verbeek, Jos H; Kateman, Erik; Morata, Thais C; Dreschler, Wouter A; Ferrite, Silvia

    2017-07-07

    This is the second update of a Cochrane Review originally published in 2009. Millions of workers worldwide are exposed to noise levels that increase their risk of hearing disorders. There is uncertainty about the effectiveness of hearing loss prevention interventions. To assess the effectiveness of non-pharmaceutical interventions for preventing occupational noise exposure or occupational hearing loss compared to no intervention or alternative interventions. We searched the CENTRAL; PubMed; Embase; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; and OSH UPDATE to 3 October 2016. We included randomised controlled trials (RCT), controlled before-after studies (CBA) and interrupted time-series (ITS) of non-clinical interventions under field conditions among workers to prevent or reduce noise exposure and hearing loss. We also collected uncontrolled case studies of engineering controls about the effect on noise exposure. Two authors independently assessed study eligibility and risk of bias and extracted data. We categorised interventions as engineering controls, administrative controls, personal hearing protection devices, and hearing surveillance. We included 29 studies. One study evaluated legislation to reduce noise exposure in a 12-year time-series analysis but there were no controlled studies on engineering controls for noise exposure. Eleven studies with 3725 participants evaluated effects of personal hearing protection devices and 17 studies with 84,028 participants evaluated effects of hearing loss prevention programmes (HLPPs). Effects on noise exposure Engineering interventions following legislationOne ITS study found that new legislation in the mining industry reduced the median personal noise exposure dose in underground coal mining by 27.7 percentage points (95% confidence interval (CI) -36.1 to -19.3 percentage points) immediately after the implementation of stricter legislation. This roughly translates to a 4.5 dB(A) decrease in

  16. Anti-inflammatory and antiresorptive effects of Calendula officinalis on inflammatory bone loss in rats.

    Science.gov (United States)

    Alexandre, Joanna Trycia M; Sousa, Luzia Hermínia Teixeira; Lisboa, Mario Roberto Pontes; Furlaneto, Flávia A C; do Val, Danielle Rocha; Marques, Mirna; Vasconcelos, Hellíada C; de Melo, Iracema Matos; Leitão, Renata; Castro Brito, Gerly Anne; Goes, Paula

    2017-12-29

    The aim of this work was to evaluate the anti-inflammatory and antiresorptive effects of Calendula officinalis (CLO) on alveolar bone loss (ABL) in rats. Male Wistar rats were subjected to ABL by ligature with nylon thread around the second upper left molar. The contralateral hemimaxillae were used as control. Rats received saline solution (SAL) or CLO (10, 30, or 90 mg/kg) 30 min before ligature and daily until the 11th day. The maxillae were removed and prepared for macroscopic, radiographic, micro-tomographic, histopathologic, histometric analysis, and immunohistochemical localization of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG). The gingival tissues were used to quantify the myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) concentrations by ELISA. Blood samples were collected for leukogram and to evaluate the bone-specific alkaline phosphatase (BALP) activity and serum levels of aspartate and alanine transaminases (AST/ALT). The bone loss induced by 11 days of ligature induced bone loss, reduced levels of BALP, leukocyte infiltration, increased MPO activity, gingival concentrations of TNF-α and IL-1β, and RANKL while reduced OPG immunoexpressions in the periodontal tissue and leukocytosis. Of the CLO, 90 mg/kg reduced bone loss, neutrophilia, the levels of pro-inflammatory mediators, and RANKL expression, while it increased OPG immunopositive cells and BALP serum levels, when compared to SAL. CLO did not affect either kidney or liver function, indicated by serum AST/ALT levels. The present data suggests that CLO reduced inflammatory bone resorption in experimental periodontitis, which may be mediated by its anti-inflammatory properties and its effects on bone metabolism. CLO can be a potential therapeutical adjuvant in the treatment of periodontitis.

  17. Vitamin K deficiency evaluated by serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa with bone loss.

    Science.gov (United States)

    Urano, Ayako; Hotta, Mari; Ohwada, Rina; Araki, Mariko

    2015-06-01

    Osteoporosis is a chief complication in patients with anorexia nervosa. Serum levels of undercarboxylated osteocalcin reflect serum and bone vitamin K deficiency. We investigated vitamin K status in patients with anorexia nervosa to help establish prevention and treatment recommendations for osteoporosis. Fifty-four female amenorrheic patients with anorexia nervosa (29 restricting-type and 25 binge eating/purging type) (age, 28.0 (26.7-31.1) (mean (95% CI)) years; body mass index, 14.8 (14.1-15.5) kg/m(2), duration of illness; 107.3 (88.5-126.0) months) and 15 age-matched healthy females were included in this study. We measured serum levels of undercarboxylated osteocalcin, biochemical and nutritional markers, and bone metabolic markers. Dietary vitamin K intake was evaluated by a questionnaire. Lumbar bone mineral density and T-scores in patients with anorexia nervosa were 0.756 (0.721-0.790) g/cm(2) and -2.4 (-2.1 to -2.7), respectively, indicating bone loss. Serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa were significantly higher than those of controls. The 17% of restricting type and 40% of binge eating/purging type anorexia nervosa patients, serum levels of undercarboxylated osteocalcin were higher than 4.5 ng/ml and were diagnosed with vitamin K deficiency. Serum levels of undercarboxylated osteocalcin correlated significantly and negatively with vitamin K intake in patients with anorexia nervosa. Patients with anorexia nervosa had vitamin K deficiency. Since a supplement of vitamin K might be effective for maintaining bone quality, we provide recommendations regarding vitamin K intake for prevention and treatment of osteoporosis in patients with AN. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  18. Alveolar bone loss and mineralization in the pig with experimental periodontal disease

    Directory of Open Access Journals (Sweden)

    Mandee Yang

    2018-03-01

    Full Text Available Objective: To address how experimental periodontal disease affects alveolar bone mass and mineral apposition in a young pig model. Materials and methods: Seven three-month-old pigs were periodically inoculated with 4 types of periodontal bacteria, along with a ligature around the last maxillary deciduous molar for 8 weeks to induce periodontal disease (PG. Eight same-aged pigs served as the control (CG. Segmentations of 3D cone-beam CT images were performed to quantify volumes of the total alveolar bone, alveolar ridge, and all roots of the target molar. Calcein and alizarin were administered for labeling mineral apposition before euthanasia. The harvested molar blocks were sectioned and examined under epifluorescence. The inter-label distance between the two vital markers at regional bone surfaces were measured and mineral apposition rate (MAR was calculated. Results: A significant reduction of total alveolar bone volume was seen in PG with the major loss at the alveolar ridge. MAR was significantly higher at the root furcation region than those at both buccal and palatal ridges in CG. Compared with CG, PG animals showed more interrupted labeled bands with significantly lower MAR at the furcation region. MARs were positively associated with both the volumes of total alveolar bone and ridge in CG, but only with the total alveolar bone in PG. Conclusions: In young growing pigs, mineral apposition is region specific. The experimental periodontal disease not only leads to alveolar bone loss, but also perturbs mineral apposition for new bone formation, thus impairing the homeostasis of alveolar bone remodeling. Keyword: Dentistry

  19. Periprosthetic bone loss: diagnostic and therapeutic approaches [v2; ref status: indexed, http://f1000r.es/3pz

    Directory of Open Access Journals (Sweden)

    Loredana Cavalli

    2014-06-01

    Full Text Available Total joint replacement surgery is being performed on an increasingly large part of the population. Clinical longevity of implants depends on their osseointegration, which is influenced by the load, the characteristics of the implant and the bone-implant interface, as well as by the quality and quantity of the surrounding bone. Aseptic loosening due to periprosthetic osteolysis is the most frequent known cause of implant failure. Wear of prosthetic materials results in the formation of numerous particles of debris that cause a complex biological response. Dual-energy X-ray Absorptiometry (DXA is regarded as an accurate method to evaluate Bone Mineral Density (BMD around hip or knee prostheses. Further data may be provided by a new device, the Bone Microarchitecture Analysis (BMA, which combines bone microarchitecture quantification and ultra high resolution osteo-articular imaging. Pharmacological strategies have been developed to prevent bone mass loss and to extend implant survival. Numerous trials with bisphosphonates show a protective effect on periprosthetic bone mass, up to 72 months after arthroplasty. Strontium ranelate has been demonstrated to increase the osseointegration of titanium implants in treated animals with improvement of bone microarchitecture and bone biomaterial properties.

  20. Design of a vehicle based system to prevent ozone loss

    Science.gov (United States)

    Lynn, Sean R.; Bunker, Deborah; Hesbach, Thomas D., Jr.; Howerton, Everett B.; Hreinsson, G.; Mistr, E. Kirk; Palmer, Matthew E.; Rogers, Claiborne; Tischler, Dayna S.; Wrona, Daniel J.

    1993-01-01

    Reduced quantities of ozone in the atmosphere allow greater levels of ultraviolet light (UV) radiation to reach the earth's surface. This is known to cause skin cancer and mutations. Chlorine liberated from Chlorofluorocarbons (CFC's) and natural sources initiate the destruction of stratospheric ozone through a free radical chain reaction. The project goals are to understand the processes which contribute to stratospheric ozone loss, examine ways to prevent ozone loss, and design a vehicle-based system to carry out the prevention scheme. The 1992/1993 design objectives were to accomplish the first two goals and define the requirements for an implementation vehicle to be designed in detail starting next year. Many different ozone intervention schemes have been proposed though few have been researched and none have been tested. A scheme proposed by R.J. Cicerone, Scott Elliot and R.P.Turco late in 1991 was selected because of its research support and economic feasibility. This scheme uses hydrocarbon injected into the Antarctic ozone hole to form stable compounds with free chlorine, thus reducing ozone depletion. Because most polar ozone depletion takes place during a 3-4 week period each year, the hydrocarbon must be injected during this time window. A study of the hydrocarbon injection requirements determined that 100 aircraft traveling Mach 2.4 at a maximum altitude of 66,000 ft. would provide the most economic approach to preventing ozone loss. Each aircraft would require an 8,000 nm. range and be able to carry 35,000 lbs. of propane. The propane would be stored in a three-tank high pressure system. Missions would be based from airport regions located in South America and Australia. To best provide the requirements of mission analysis, an aircraft with L/D(sub cruise) = 10.5, SFC = 0.65 (the faculty advisor suggested that this number is too low) and a 250,000 lb TOGW was selected as a baseline. Modularity and multi-role functionality were selected to be key

  1. Mice with increased angiogenesis and osteogenesis due to conditional activation of HIF pathway in osteoblasts are protected from ovariectomy induced bone loss.

    Science.gov (United States)

    Zhao, Qiang; Shen, Xing; Zhang, Wei; Zhu, Guochun; Qi, Jin; Deng, Lianfu

    2012-03-01

    Postmenopausal osteoporosis is characterized by a reduction in the numbers of sinusoidal and arterial capillaries in the bone marrow and reduced bone perfusion suggesting a role of vascular component in the pathogenesis of osteoporosis. Previous studies have shown that bone formation and angiogenesis are positively coupled through activation of the hypoxia inducible factor (HIF1α) signaling pathway. Therefore, we hypothesized that mice with increased angiogenesis and osteogenesis due to activation of the HIF signaling pathway in osteoblasts, via osteoblast specific disruption of HIF degrading protein von Hippel-Lindau (VHL) (ΔVhl), are protected from ovariectomy induced bone loss. ΔVhl mice and control littermates were ovariectomized or sham operated and four weeks later bone quality was evaluated along with blood vessel formation. Trabecular and cortical bone volume was strikingly increased in ΔVhl mice along with blood vessel formation as compared to control littermates. In control mice, ovariectomy significantly decreased bone mineral density, deteriorated bone microarchitecture, and decreased mechanical strength compared to the sham operated control mice. This was accompanied with a significant decrease in blood vessel volume and expressions of HIF1α, HIF2α, and VEGF proteins at the distal femur in ovariectomized control mice. In contrast, ovariectomy in ΔVhl mice had absolutely no effect on either the blood vessel formation or the bone structural and mechanical quality parameters. These data indicate that activation of HIF signaling pathway in osteoblasts may prevent estrogen deficiency-induced bone loss and decrease in blood vessels in bone marrow. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Effect of trabecular bone loss on cortical strain rate during impact in an in vitro model of avian femur

    Directory of Open Access Journals (Sweden)

    Gefen Amit

    2006-07-01

    Full Text Available Abstract Background Osteoporotic hip fractures occur due to loss of cortical and trabecular bone mass and consequent degradation in whole bone strength. The direct cause of most fractures is a fall, and hence, characterizing the mechanical behavior of a whole osteopenic bone under impact is important. However, very little is known about the mechanical interactions between cortical and trabecular bone during impact, and it is specifically unclear to what extent epiphyseal trabecular bone contributes to impact resistance of whole bones. We hypothesized that trabecular bone serves as a structural support to the cortex during impact, and hence, loss of a critical mass of trabecular bone reduces internal constraining of the cortex, and, thereby, decreases the impact tolerance of the whole bone. Methods To test this hypothesis, we conducted cortical strain rate measurements in adult chicken's proximal femora subjected to a Charpy impact test, after removing different trabecular bone core masses to simulate different osteopenic severities. Results We found that removal of core trabecular bone decreased by ~10-fold the cortical strain rate at the side opposite to impact (p Conclusion We conclude that in our in vitro avian model, loss of over 10% of core trabecular bone substantially altered the deformation response of whole bone to impact, which supports the above hypothesis and indicates that integrity of trabecular bone is critical for resisting impact loads.

  3. [Effects of Chinese Bushen Zhuanggu medicine on bone loss in female rats after simulated weightlessness].

    Science.gov (United States)

    Sun, Ping; Huang, Zhen; Cai, De-Hong; He, Lei

    2007-02-01

    To study the effect of Bushen Zhuanggu, the traditional Chinese medicine for reinforcing kidney and strengthening bone, on bone loss in female rats after simulated weightlessness. Thirty-six female SD rats were randomly divided into 3 groups, namely normal control group (group A) and two groups of weightlessness simulated by tail suspension (groups B and C). Group C were treated with the Chinese medicine, while groups A and B were given the same dose of normal saline. The experiment lasted 28 days, and all rats were allowed to drink water freely. In the rats of group B, serum bone Gla protein (BGP), alkaline phosphatase (ALP), estradiol (E(2)) and P content and femur bone mineral content (BMD) were significantly lower than those in group A (P<0.01, P<0.05), whereas serum calcium concentration was markedly higher than that in group A (P<0.01). In rats of group C, serum BGP, ALP, E2 and P content and femur BMD were significantly higher than those in group B (P<0.01, P<0.05), but serum calcium concentration was markedly lower (P<0.01). This Chinese prescription can stimulate bone formation and reduce bone loss in female rats subjected to simulated weightlessness.

  4. Cannabidiol administration reduces sublesional cancellous bone loss in rats with severe spinal cord injury.

    Science.gov (United States)

    Li, Dehao; Lin, Zilin; Meng, Qingyi; Wang, Kun; Wu, Jiajia; Yan, Hongda

    2017-08-15

    Patients with spinal cord injury (SCI) undergo severe loss of bone mineral below the level of lesion, and data on available treatment options after SCI is scarce. The aim of this work was to investigate the therapeutic effect of cannabidiol (CBD), a non-psychoactive cannabis, on sublesional bone loss in a rat model of SCI. The adult male rats were exposed to surgical transection of the cord and treated with CBD for consecutive 14 days. It was found that CBD treatment elevated the serum levels of osteocalcin, reduced the serum levels of collagen type I cross-linked C-telopeptide, and enhanced bone mineral density of tibiae and femurs. Treatment of SCI rats with CBD enhanced bone volume, trabecular thickness, and trabecular number, and reduced trabecular separation in proximal tibiae, and increased ultimate compressive load, stiffness, and energy to max force of femoral diaphysis. Treatment of SCI rats with CBD upregulated mRNA expression of alkaline phosphatase and osteoprotegerin and downregulated mRNA expression of receptor activator of NF-κB ligand and tartrate-resistant acid phosphatase in femurs. Furthermore, treatment of SCI rats with CBD enhanced mRNA expression of wnt3a, Lrp5 and ctnnb1 in femurs. In conclusion, CBD administration attenuated SCI-induced sublesional cancellous bone loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Muscular strength measurements indicate bone mineral density loss in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Zhou Z

    2013-10-01

    measurements were identified for different age groups. Age-appropriate testing mode can improve detection of osteoporotic fracture risk in early menopause by determining muscular strength reduction related to BMD loss. This may enable early initiation of preventative therapies. Keywords: osteoporosis, fracture, bone mineral density, postmenopausal, menopause, muscle strength, isokinetic, isometric

  6. Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte hypertrophy develop in the long bones of postnatal Ext1-deficient mice.

    Science.gov (United States)

    Sgariglia, Federica; Candela, Maria Elena; Huegel, Julianne; Jacenko, Olena; Koyama, Eiki; Yamaguchi, Yu; Pacifici, Maurizio; Enomoto-Iwamoto, Motomi

    2013-11-01

    Long bones are integral components of the limb skeleton. Recent studies have indicated that embryonic long bone development is altered by mutations in Ext genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in activity and distribution of HS-binding/growth plate-associated signaling proteins. Here we asked whether Ext function is continuously required after birth to sustain growth plate function and long bone growth and organization. Compound transgenic Ext1(f/f);Col2CreERT mice were injected with tamoxifen at postnatal day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1-deficient mice exhibited growth retardation already by 2weeks post-injection, as did their long bones. Mutant growth plates displayed a severe disorganization of chondrocyte columnar organization, a shortened hypertrophic zone with low expression of collagen X and MMP-13, and reduced primary spongiosa accompanied, however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous border. The mutant epiphyses were abnormal as well. Formation of a secondary ossification center was significantly delayed but interestingly, hypertrophic-like chondrocytes emerged within articular cartilage, similar to those often seen in osteoarthritic joints. Indeed, the cells displayed a large size and round shape, expressed collagen X and MMP-13 and were surrounded by an abundant Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In addition, ectopic cartilaginous outgrowths developed on the lateral side of mutant growth plates over time that resembled exostotic characteristic of children with Hereditary Multiple Exostoses, a syndrome caused by Ext mutations and HS deficiency. In sum, the data do show that Ext1 is continuously required for postnatal growth and organization of long bones as well as their adjacent joints. Ext1 deficiency elicits defects that can occur in human skeletal conditions including trabecular bone loss

  7. 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.

  8. Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Morton, M.S.; Brüggemann-Rotgans, I.E.M.; Beresteijn, E.C.H. van

    1998-01-01

    Objective: The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. Design: Secondary analysis of a 10-year follow-up study (1979-1989) among postmenopausal women in the

  9. Stemmed femoral knee prostheses: effects of prosthetic design and fixation on bone loss.

    NARCIS (Netherlands)

    Lenthe, G.H. van; Willems, P.C.P.H.; Verdonschot, N.J.J.; Waal Malefijt, M.C. de; Huiskes, R.

    2002-01-01

    Although the revision rates for modern knee prostheses have decreased drastically, the total number of revisions a year is increasing because many more primary knee replacements are being done. At the time of revision, bone loss is common, which compromises prosthetic stability. To improve

  10. Java project on periodontal diseases: periodontal bone loss in relation to environmental and systemic conditions

    NARCIS (Netherlands)

    Amaliya, A.; Laine, M.L.; Delanghe, J.R.; Loos, B.G.; van Wijk, A.J.; van der Velden, U.

    2015-01-01

    Objective To assess in a population deprived from regular dental care the relationship between alveolar bone loss (ABL) and environmental/systemic conditions. Material & Methods The study population consisted of subjects from the Purbasari tea estate on West Java, Indonesia. A full set of dental

  11. Validation of a dental image analyzer tool to measure alveolar bone loss in periodontitis patients

    NARCIS (Netherlands)

    Teeuw, W.J.; Coelho, L.; de Silva, A.; van der Palen, C.J.N.M.; Lessmann, F.G.J.M.; van der Velden, U.; Loos, B.G.

    2009-01-01

    Background and Objective:  Radiographs are an essential adjunct to the clinical examination for periodontal diagnoses. Over the past few years, digital radiographs have become available for use in clinical practice. Therefore, the present study investigated whether measuring alveolar bone loss,

  12. Mandibular fracture caused by peri-implant bone loss : Report of a case

    NARCIS (Netherlands)

    Meijer, Henny J. A.; Raghoebar, Gerry M.; Visser, Anita

    Background: A major complication related to excessive bone loss around implants is fracture of the mandible. This complication is most likely to occur in a very atrophic mandible. A 57-year-old woman presented with progressive pain and swelling that had been present for 5 days in the right frontal

  13. Hindfoot arthrodesis for management of bone loss following calcaneus fractures and nonunions.

    Science.gov (United States)

    Molloy, Andy P; Lipscombe, Stephen J

    2011-03-01

    Massive bone loss following calcaneal fractures is a challenging condition to treat, especially if nonunion is present. Meticulous preoperative examination and imaging are crucial for accurate preoperative planning. If performed, successful outcomes can be achieved with the strategies outlined in this article. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Dental Implant Thread Design and the Consequences on Long-Term Marginal Bone Loss.

    Science.gov (United States)

    Ormianer, Zeev; Matalon, Shlomo; Block, Jonathan; Kohen, Jerry

    2016-08-01

    The aim of this study was to present the implant macrostructure effect on marginal bone loss using 3 dental implant thread designs with differences in thread pitch, lead, and helix angle. All implants used were sourced from the same company and had the same microstructured surface. This is a nonrandomized, retrospective, double-blind study. Data were collected by an independent Tel Aviv University group from a general practitioner's private practice patient records. In total, 1361 implants met the inclusion criteria representing the 3 types of implants macrostructure. Overall survival rate was 96.3% with 50 implants failing (3.7%) out of a total of 1361 implants. Survival rates for the 3 groups were: group A 96.6%, group B 95.9%, and in group C 100%. Average bone loss for groups A, B, and C were 2.02 (±1.70) mm, 2.10 (±1.73) mm, and 1.90 (±1.40) mm, respectively. Pairwise comparisons revealed that less bone loss occurred in group A compared with group B (P = 0.036). Favorable long-term bone loss results were found in implants with a larger pitch, deeper apical threads, and a narrower implant core. One-piece V-thread design implants demonstrated 100% survival rate.

  15. Coincidence of calcified carotid atheromatous plaque, osteoporosis, and periodontal bone loss in dental panoramic radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Ramesh, Aruna; Ganguly, Rumpa [Dept. of Diagnosis and Health Promotion, Division of Oral and Maxillofacial Radiology, Tufts University School of Dental Medicine, Boston (United States); Soroushian, Sheila [Dept. of Orthodontics, Howard University College of Dentistry, Washington, DC(United States)

    2013-12-15

    This study was performed to assess the correlation of calcified carotid atheromatous plaque (CCAP), the mandibular cortical index, and periodontal bone loss in panoramic radiographs. One hundred eighty-five panoramic radiographs with CCAP and 234 without this finding were evaluated by 3 observers for the presence of osseous changes related to osteoporosis and periodontal bone loss. Chi-squared and Mann-Whitney U tests were used to compare the two groups for an association of CCAP with the mandibular cortical index and periodontal bone loss, respectively. There was a statistically significant coincidence of CCAP and osseous changes related to osteopenia/osteoporosis, with a p-value <0.001. There was no statistically significant coincidence of CCAP and periodontal bone loss. When comparing the 2 groups, 'With CCAP' and 'Without CCAP', there was a statistically significant association with the mean body mass index (BMI), number of remaining teeth, positive history of diabetes mellitus, and vascular accidents. There was no statistically significant association with gender or a history of smoking. This study identified a possible concurrence of CCAP and mandibular cortical changes secondary to osteopenia/osteoporosis in panoramic radiographs. This could demonstrate the important role of dental professionals in screening for these systemic conditions, leading to timely and appropriate referrals resulting in early interventions and thus improving overall health.

  16. Coincidence of calcified carotid atheromatous plaque, osteoporosis, and periodontal bone loss in dental panoramic radiographs

    International Nuclear Information System (INIS)

    Ramesh, Aruna; Ganguly, Rumpa; Soroushian, Sheila

    2013-01-01

    This study was performed to assess the correlation of calcified carotid atheromatous plaque (CCAP), the mandibular cortical index, and periodontal bone loss in panoramic radiographs. One hundred eighty-five panoramic radiographs with CCAP and 234 without this finding were evaluated by 3 observers for the presence of osseous changes related to osteoporosis and periodontal bone loss. Chi-squared and Mann-Whitney U tests were used to compare the two groups for an association of CCAP with the mandibular cortical index and periodontal bone loss, respectively. There was a statistically significant coincidence of CCAP and osseous changes related to osteopenia/osteoporosis, with a p-value <0.001. There was no statistically significant coincidence of CCAP and periodontal bone loss. When comparing the 2 groups, 'With CCAP' and 'Without CCAP', there was a statistically significant association with the mean body mass index (BMI), number of remaining teeth, positive history of diabetes mellitus, and vascular accidents. There was no statistically significant association with gender or a history of smoking. This study identified a possible concurrence of CCAP and mandibular cortical changes secondary to osteopenia/osteoporosis in panoramic radiographs. This could demonstrate the important role of dental professionals in screening for these systemic conditions, leading to timely and appropriate referrals resulting in early interventions and thus improving overall health.

  17. Effect of dietary soy isoflavones on bone loss in ovariectomized rats

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research January 2018; 17 (1): 91-96 .... B. M. D. (g/cm. 2. ) group. **. *. Figure 3: Soy isoflavone supplementation suppresses the reduction of BMD (g/cm2) in OVX rats. 1, intact rats; 2, untreated OVX rats; 3–5, OVX rats treated .... Estrogen deficiency associated bone loss in the maxilla: ...

  18. No major effect of estrogen receptor gene polymorphisms on bone mineral density or bone loss in postmenopausal Danish women

    DEFF Research Database (Denmark)

    Bagger, Y Z; Jørgensen, H L; Heegaard, Anne-Marie

    2000-01-01

    The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment......-length polymorphisms of the ER gene with BMD in Danish postmenopausal women, two studies were undertaken: 1) a cross-sectional study of 499 postmenopausal women, where the ER genotypes and alleles were related to BMD of the hip, spine, and lower forearm; and 2) a longitudinal study of 101 postmenopausal women followed...... up for 18 years. In the latter study, late postmenopausal bone loss in the hip and spine was determined over a period of 6 years in women (mean age of 63 to 69 years), and long-term postmenopausal bone loss in the lower forearm was determined over a period of 18 years in women (mean age of 51 to 69...

  19. Site-specific variability in trabecular bone dosimetry: Considerations of energy loss to cortical bone

    International Nuclear Information System (INIS)

    Patton, P.W.; Rajon, D.A.; Shah, A.P.; Jokisch, D.W.; Inglis, B.A.; Bolch, W.E.

    2002-01-01

    With continual advances in radionuclide therapies, increasing emphasis is being placed on improving the patient specificity of dose estimates to marrow tissues. While much work has been focused on determining patient-specific assessments of radionuclide uptake in the skeleton, few studies have been initiated to explore the individual variability of absorbed fraction data for electron and beta-particle sources in various skeletal sites. The most recent values of radionuclide S values used in clinical medicine continue to utilize a formalism in which electrons are transported under a trabecular bone geometry of infinite extent. No provisions are thus made for the fraction of energy lost to the cortical bone cortex of the skeletal site and its surrounding tissues. In the present study, NMR microscopy was performed on trabecular bone samples taken from the femoral head and humeral proximal epiphysis of three subjects: a 51-year male, an 82-year female, and an 86-year female. Following image segmentation and coupling to EGS4, electrons were transported within macrostructural models of the various skeletal sites that explicitly include the spatial extent of the spongiosa, as well as the thickness of the surrounding cortical bone. These energy-dependent profiles of absorbed fractions to marrow tissues were then compared to transport simulations made within an infinite region of spongiosa. Ratios of mean absorbed fraction, as weighted by the beta energy spectra, under both transport methodologies were then assembled for the radionuclides 32 P and 90 Y. These ratios indicate that corrections to existing radionuclide S values for 32 P can vary by as much as 5% for the male, 6% for the 82-year female, and 8% for the 86-year female. For the higher-energy beta spectrum of 90 Y, these same corrections can reach 8%, 10%, and 11%, respectively

  20. Inactivity-induced bone loss is not exacerbated by moderate energy restriction

    Science.gov (United States)

    Heer, M.; Boese, A.; Baecker, N.; Zittermann, A.; Smith, S. M.

    Severe energy restriction leads to decreased bone mineral density (BMD) in postmenopausal women, adolescent females, and in male athletes. Astronauts in space also lose bone mass, and most of them have reduced energy intake (about 25 % below requirements). The aim of our study was to examine if bone loss in space is partly induced by moderate energy restriction. Physiological changes of space flight were simulated by 6 head-down tilt bed rest (HDBR). Nine healthy male subjects (age: 23.6 ± 3.0 years; BMI: 23.0 ± 2.9 kg/m2, mean ± SD) finished four study phases, two of normocaloric nutrition, either ambulatory or HDBR, and two of hypocaloric nutrition, either ambulatory or HDBR. Urine samples (24 h) were analyzed for calcium excretion (UCaV) and bone resorption markers (C-Telopeptide, CTX, and N-Telopeptide, NTX). Serum calcium, parathyroid hormone (PTH) and bone formation markers (Procollagen-I-C-terminal-Peptide, PICP, Procollagen-I-N-terminal-Peptide, PINP, and bone-specific alkaline phosphatase, bAP) were analyzed. No significant changes in serum calcium or PTH were noted either during HDBR or during hypocaloric nutrition. PICP, but not PINP or bAP, decreased significantly during HDBR (normocaloric: pnutrition or both (pnutrition in ambulatory and HDBR phases. In conclusion, moderate energy restriction did not exaggerate bone resorption during HDBR.

  1. Three-dimensional measurement of bone loss at implants in patients with periodontal disease.

    Science.gov (United States)

    Kehl, Marcus; Swierkot, Katrin; Mengel, Reiner

    2011-05-01

    The aim of this prospective study is to evaluate the three-dimensional marginal bone level around implants 5 to 15 years after loading in partially edentulous patients treated for generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAgP). Seventeen patients with GCP and 17 patients with GAgP were treated with a total of 119 implants. Patients were examined clinically on a 3-month recall schedule after insertion of the superstructure, and radiographs were taken at fixed intervals. At the end of the observation period, cone-beam computed tomography was used for the analysis of the circumferential three-dimensional bone level (mesial, distal, buccal, and lingual/palatal) and determination of keratinized mucosa thickness (KMT). In both groups, a significant bone loss at implants was observed buccally (GAgP group: 4.49 ± 2.93 mm; GCP group: 3.57 ± 2.94 mm) with significantly more average bone loss in patients with GAgP (3.00 ± 1.67 mm) compared to in patients with GCP (2.45 ± 1.08 mm). The lowest values for KMT in both groups were found in the anterior mandible (GAgP group: 0.99 ± 1.13 mm; GCP group: 0.82 ± 0.91 mm). There were significant correlations between clinical parameters and bone loss in mandibles of patients with GAgP. The lowest value for KMT in both groups was found in the mandible. Bone loss was observed buccally and was more pronounced in patients with GAgP, with a significant correlation with keratinized mucosa and increased inflammation.

  2. Dietary flavonoid kaempferol inhibits glucocorticoid-induced bone loss by promoting osteoblast survival.

    Science.gov (United States)

    Adhikary, Sulekha; Choudhary, Dharmendra; Ahmad, Naseer; Karvande, Anirudha; Kumar, Avinash; Banala, Venkatesh Teja; Mishra, Prabhat Ranjan; Trivedi, Ritu

    2018-02-13

    Kaempferol, a dietary flavonoid found in fruits and vegetables, has been reported to reverse osteopenic condition in ovariectomized rats. Because kaempferol is endowed with osteogenic activity, the aim of this study was to determine whether it has a beneficial effect on glucocorticoid (GC)-induced bone loss. Adult female rats were divided into four groups as control (vehicle; distilled water), methylprednisolone (MP; 5 mg•kg•d, subcutaneously), MP + kaempferol (5 mg•kg•d, oral), and MP + human parathyroid 1-34 (30 µg/kg, 5 times/wk, subcutaneously) and treated for 4 wk. To study the antagonizing effect of kaempferol on GC-induced inhibition of fracture healing, drill-hole injury was performed on control and GC-treated rats. An oral dose of kaempferol was given for 14 d to observe the effect on callus formation at the site of injury. After treatment, bones were collected for further analysis. GC was associated with a decreased bone mineral density and impaired bone microarchitecture parameters. Consumption of kaempferol induced bone-sparing effects in GC-induced osteopenic condition. Additionally, improved callus formation at site of drill injury in femur diaphysis was observed with kaempferol consumption in animals on GC. Consistent with the in vivo data, kaempferol elicited a higher expression of osteogenic markers in vitro and antagonized the apoptotic effect of dexamethasone on calvarial osteoblasts. These results suggested that kaempferol reduced GC-induced bone loss and enhanced bone regeneration at fractured site, thus emphasizing the positive role of flavonoids on bone health. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Inhibitory Effects of KP-A159, a Thiazolopyridine Derivative, on Osteoclast Differentiation, Function, and Inflammatory Bone Loss via Suppression of RANKL-Induced MAP Kinase Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Hye Jung Ihn

    Full Text Available Abnormally elevated formation and activation of osteoclasts are primary causes for a majority of skeletal diseases. In this study, we found that KP-A159, a newly synthesized thiazolopyridine derivative, inhibited osteoclast differentiation and function in vitro, and inflammatory bone loss in vivo. KP-A159 did not cause a cytotoxic response in bone marrow macrophages (BMMs, but significantly inhibited the formation of multinucleated tartrate-resistant acid phosphatase (TRAP-positive osteoclasts induced by macrophage colony-stimulating factor (M-CSF and receptor activator of nuclear factor-κB ligand (RANKL. KP-A159 also dramatically inhibited the expression of marker genes related to osteoclast differentiation, including TRAP (Acp5, cathepsin K (Ctsk, dendritic cell-specific transmembrane protein (Dcstamp, matrix metallopeptidase 9 (Mmp9, and nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1. Moreover, actin ring and resorption pit formation were inhibited by KP-A159. Analysis of the signaling pathway involved showed that KP-A159 inhibited RANKL-induced activation of extracellular signal-regulated kinase (ERK, c-Jun N-terminal kinase (JNK, and mitogen-activated protein kinase kinase1/2 (MEK1/2. In a mouse inflammatory bone loss model, KP-A159 significantly rescued lipopolysaccharide (LPS-induced bone loss by suppressing osteoclast numbers. Therefore, KP-A159 targets osteoclasts, and may be a potential candidate compound for prevention and/or treatment of inflammatory bone loss.

  4. Comparative Evaluation of the Prevalence of Maxillary Sinus Mucosal Thickening in the Patients with Periodontal Bone Loss: A Digital Panoramic Study

    Directory of Open Access Journals (Sweden)

    S Mirbeigi

    2015-07-01

    Results: Mucosal thickening was significantly correlated with the bone loss and pattern type of the bone loss. Moreover, the prevalence of sinus mucosal thickening was 12.10% in patients with mild bone loss, 27.45% in patients with moderate bone loss, 63.15% in patients with severe bone loss. No statistically significant relationship was detected between Maxillary sinus mucositis with patients’ age and sex (p =0.05. Conclusion: In patients suffering from the bone loss, increased severity of the bone loss can lead to an increase in the prevalence of sinus mucosal thickening. The maxillary sinus mucositis was reported to be more prevalent in the bone loss with a vertical pattern rather than the bone loss with a horizontal pattern. Moreover, based on the results of the present study, the periodontal disease may increase the risk of sinus mucosal thickening.

  5. Methoxsalen supplementation attenuates bone loss and inflammatory response in ovariectomized mice.

    Science.gov (United States)

    Ham, Ju Ri; Choi, Ra-Yeong; Yee, Sung-Tae; Hwang, Yun-Ho; Kim, Myung-Joo; Lee, Mi-Kyung

    2017-12-25

    Methoxsalen (MTS) is a natural bioactive compound found in a variety of plants that has many known biofunctions; however, its effects on osteoporosis and related mechanisms are not clear. This study examined whether MTS exhibited preventive effects against postmenopausal osteoporosis. Female C3H/HeN mice were divided into four groups: Sham, ovariectomy (OVX), OVX with MTS (0.02% in diet), and OVX with estradiol (0.03 μg/day, s.c). After 6 weeks, MTS supplementation significantly increased femur bone mineral density and bone surface along with bone surface/total volume. MTS significantly elevated the levels of serum formation markers (estradiol, osteocalcin and bone-alkaline phosphatase) such as estradiol in OVX mice. Tartrate resistant acid phosphatase staining revealed that MTS suppressed osteoclast numbers and formation in femur tissues compared with the OVX group. Supplementation of MTS slightly up-regulated osteoblastogenesis-related genes (Runx-2, osterix, osteocalcin, and Alp) expression, whereas it significantly down-regulated inflammatory genes (Nfκb and Il6) expression in femur tissue compared with the OVX group. These results indicate that MTS supplementation effectively prevented OVX-induced osteoporosis via enhancement of bone formation and suppression of inflammatory response in OVX mice. Our study provides valid scientific information regarding the development and application of MTS as a food ingredient, a food supplement or an alternative agent for preventing postmenopausal osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Loss of bone strength in HLA-B27 transgenic rats is characterized by a high bone turnover and is mainly osteoclast-driven.

    Science.gov (United States)

    Rauner, Martina; Thiele, Sylvia; Fert, Ingrid; Araujo, Luiza M; Layh-Schmitt, Gerlinde; Colbert, Robert A; Hofbauer, Christine; Bernhardt, Ricardo; Bürki, Alexander; Schwiedrzik, Jakob; Zysset, Philippe K; Pietschmann, Peter; Taurog, Joel D; Breban, Maxime; Hofbauer, Lorenz C

    2015-06-01

    Although osteopenia is frequent in spondyloarthritis (SpA), the underlying cellular mechanisms and association with other symptoms are poorly understood. This study aimed to characterize bone loss during disease progression, determine cellular alterations, and assess the contribution of inflammatory bowel disease (IBD) to bone loss in HLA-B27 transgenic rats. Bones of 2-, 6-, and 12-month-old non-transgenic, disease-free HLA-B7 and disease-associated HLA-B27 transgenic rats were examined using peripheral quantitative computed tomography, μCT, and nanoindentation. Cellular characteristics were determined by histomorphometry and ex vivo cultures. The impact of IBD was determined using [21-3 x 283-2]F1 rats, which develop arthritis and spondylitis, but not IBD. HLA-B27 transgenic rats continuously lost bone mass with increasing age and had impaired bone material properties, leading to a 3-fold decrease in bone strength at 12 months of age. Bone turnover was increased in HLA-B27 transgenic rats, as evidenced by a 3-fold increase in bone formation and a 6-fold increase in bone resorption parameters. Enhanced osteoclastic markers were associated with a larger number of precursors in the bone marrow and a stronger osteoclastogenic response to RANKL or TNFα. Further, IBD-free [21-3 x 283-2]F1 rats also displayed decreased total and trabecular bone density. HLA-B27 transgenic rats lose an increasing amount of bone density and strength with progressing age, which is primarily mediated via increased bone remodeling in favor of bone resorption. Moreover, IBD and bone loss seem to be independent features of SpA in HLA-B27 transgenic rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Correlation analysis of alveolar bone loss in buccal/palatal and proximal surfaces in rats

    Directory of Open Access Journals (Sweden)

    Carolina Barrera de Azambuja

    2012-12-01

    Full Text Available The aim was to correlate alveolar bone loss in the buccal/palatal and the mesial/distal surfaces of upper molars in rats. Thirty-three, 60-day-old, male Wistar rats were divided in two groups, one treated with alcohol and the other not treated with alcohol. All rats received silk ligatures on the right upper second molars for 4 weeks. The rats were then euthanized and their maxillae were split and defleshed with sodium hypochlorite (9%. The cemento-enamel junction (CEJ was stained with 1% methylene blue and the alveolar bone loss in the buccal/palatal surfaces was measured linearly in 5 points on standardized digital photographs. Measurement of the proximal sites was performed by sectioning the hemimaxillae, restaining the CEJ and measuring the alveolar bone loss linearly in 3 points. A calibrated and blinded examiner performed all the measurements. Intraclass Correlation Coefficient revealed values of 0.96 and 0.89 for buccal/lingual and proximal surfaces, respectively. The Pearson Correlation Coefficient (r between measurements in buccal/palatal and proximal surfaces was 0.35 and 0.05 for the group treated with alcohol, with and without ligatures, respectively. The best correlations between buccal/palatal and proximal surfaces were observed in animals not treated with alcohol, in sites both with and without ligatures (r = 0.59 and 0.65, respectively. A positive correlation was found between alveolar bone loss in buccal/palatal and proximal surfaces. The correlation is stronger in animals that were not treated with alcohol, in sites without ligatures. Areas with and without ligature-induced periodontal destruction allow detection of alveolar bone loss in buccal/palatal and proximal surfaces.

  8. Toll-Like Receptor 4 Signaling Pathway Mediates Inhalant Organic Dust-Induced Bone Loss.

    Directory of Open Access Journals (Sweden)

    Elizabeth Staab

    Full Text Available Agriculture workers have increased rates of airway and skeletal disease. Inhalant exposure to agricultural organic dust extract (ODE induces bone deterioration in mice; yet, mechanisms underlying lung-bone crosstalk remain unclear. Because Toll-like receptor 2 (TLR2 and TLR4 are important in mediating the airway consequences of ODE, this study investigated their role in regulating bone responses. First, swine facility ODE stimulated wild-type (WT bone marrow macrophages to form osteoclasts, and this finding was inhibited in TLR4 knock-out (KO, but not TLR2 KO cells. Next, using an established intranasal inhalation exposure model, WT, TLR2 KO and TLR4 KO mice were treated daily with ODE or saline for 3 weeks. ODE-induced airway neutrophil influx and cytokine/chemokine release were similarly reduced in TLR2 and TLR4 KO animals as compared to WT mice. Utilizing micro-computed tomography (CT, analysis of tibia showed loss of bone mineral density, volume and deterioration of bone micro-architecture and mechanical strength induced by ODE in WT mice were significantly reduced in TLR4 but not TLR2 KO animals. Bone marrow osteoclast precursor cell populations were analyzed by flow cytometry from exposed animals. In WT animals, exposure to inhalant ODE increased osteoclast precursor cell populations as compared to saline, an effect that was reduced in TLR4 but not TLR2 KO mice. These results show that TLR2 and TLR4 pathways mediate ODE-induced airway inflammation, but bone deterioration consequences following inhalant ODE treatment is strongly dependent upon TLR4. Thus, the TLR4 signaling pathway appears critical in regulating the lung-bone inflammatory axis to microbial component-enriched organic dust exposures.

  9. Arctic Ground Squirrels Limit Bone Loss during the Prolonged Physical Inactivity Associated with Hibernation.

    Science.gov (United States)

    Wojda, Samantha J; Gridley, Richard A; McGee-Lawrence, Meghan E; Drummer, Thomas D; Hess, Ann; Kohl, Franziska; Barnes, Brian M; Donahue, Seth W

    2016-01-01

    Prolonged disuse (e.g., physical inactivity) typically results in increased bone porosity, decreased mineral density, and decreased bone strength, leading to increased fracture risk in many mammals. However, bears, marmots, and two species of ground squirrels have been shown to preserve macrostructural bone properties and bone strength during long seasons of hibernation while they remain mostly inactive. Some small hibernators (e.g., 13-lined ground squirrels) show microstructural bone loss (i.e., osteocytic osteolysis) during hibernation, which is not seen in larger hibernators (e.g., bears and marmots). Arctic ground squirrels (Urocitellus parryii) are intermediate in size between 13-lined ground squirrels and marmots and are perhaps the most extreme rodent hibernator, hibernating for up to 8 mo annually with body temperatures below freezing. The goal of this study was to quantify the effects of hibernation and inactivity on cortical and trabecular bone properties in arctic ground squirrels. Cortical bone geometrical properties (i.e., thickness, cross-sectional area, and moment of inertia) at the midshaft of the femur were not different in animals sampled over the hibernation and active seasons. Femoral ultimate stress tended to be lower in hibernators than in summer animals, but toughness was not affected by hibernation. The area of osteocyte lacunae was not different between active and hibernating animals. There was an increase in osteocytic lacunar porosity in the hibernation group due to increased lacunar density. Trabecular bone volume fraction in the proximal tibia was unexpectedly greater in the hibernation group than in the active group. This study shows that, similar to other hibernators, arctic ground squirrels are able to preserve many bone properties during hibernation despite being physically inactive for up to 8 mo.

  10. Loss of the PGE2 receptor EP1 enhances bone acquisition, which protects against age and ovariectomy-induced impairments in bone strength.

    Science.gov (United States)

    Zhang, Minjie; Feigenson, Marina; Sheu, Tzong-jen; Awad, Hani A; Schwarz, Edward M; Jonason, Jennifer H; Loiselle, Alayna E; O'Keefe, Regis J

    2015-03-01

    PGE2 exerts anabolic and catabolic effects on bone through the discrete actions of four prostanoid receptors (EP1-4). We have previously demonstrated that loss EP1 accelerates fracture repair by enhancing bone formation. In the present study we defined the role of EP1 in bone maintenance and homeostasis during aging and in response to ovariectomy. The femur and L4 vertebrae of wild type (WT) and EP1(-/-) mice were examined at 2-months, 6-months, and 1-year of age, and in WT and EP1(-/-) mice following ovariectomy (OVX) or sham surgery. Bone volume fraction, trabecular architecture and mechanical properties were maintained during aging in EP1(-/-) mice to a greater degree than age-matched WT mice. Moreover, significant increases in bone formation rate (BFR) (+60%) and mineral apposition rate (MAR) (+50%) were observed in EP1(-/-), relative to WT, while no change in osteoclast number and osteoclast surface were observed. Following OVX, loss of EP1 was protective against bone loss in both femur and L4 vertebrae, with increased bone volume/total volume (BV/TV) (+32% in femur) and max load at failure (+10% in femur) relative to WT OVX, likely resulting from the increased bone formation rate that was observed in these mice. Taken together these studies identify inhibition of EP1 as a potential therapeutic approach to suppress bone loss in aged or post-menopausal patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Evaluation of the Stress Induced in Tooth, Periodontal Ligament & Alveolar Bone with Varying Degrees of Bone Loss During Various Types of Orthodontic Tooth Movements.

    Science.gov (United States)

    Agarwal, Anupam; Mahajan, Shalu; Verma, Santosh; Bhardwaj, Preeti; Sharma, Geeta

    2016-02-01

    The force applied on to a tooth with periodontal bone loss may generate different magnitude and pattern of stresses in the periodontium when compared to a tooth with no bone loss & under the same force system. The intensity of the forces and moment to force ratios needed to be applied during an Orthodontic treatment must be adapted to obtain the same movement as in a tooth with a healthy periodontal support. Evaluation and assessment of the stress distribution during various types of Orthodontic tooth movement on application of Orthodontic force, at various levels of alveolar bone loss; & determination of the most ideal force system producing the Optimum Stress (i.e., stress within optimum range), uniformly (conducive to bodily movement of maxillary canine with varying degrees of bone loss). A human maxillary canine tooth of right side was simulated by means of Finite Element Method (FEM). Five different models were constructed with bone loss ranging from 0mm in model 1, to 8mm in model 5 (progressing at 2mm per model). Ten different loading conditions were applied on these models and the stress generated was charted at various occluso-gingival levels and surfaces around the tooth. The evaluation and assessment of the stress distribution during various types of Orthodontic tooth movement on application of Orthodontic force, at various levels of alveolar bone loss was done. The results showed that there was a high positive correlation between the increase in bone loss & the stress generated, suggesting an elevation in the stress with advancing bone loss. Additionally, the type of tooth movement was found to be changed with bone loss. During the determination of ideal force system it was found that the centre of resistance of the canine migrated apically with bone loss and an increase in the moment to force ratio (Mc:F) was required to control the root position in these cases. A high positive correlation exists between the increase in bone loss and the stress

  12. Marginal bone loss and dental implant failure may be increased in smokers.

    Science.gov (United States)

    Veitz-Keenan, Analia

    2016-03-01

    An electronic search was performed in PubMed, Web of Science and the Cochrane Central Register of Controlled Trials up to February 2015. References of included studies were also searched. No language restrictions were applied. Study selection: Prospective, retrospective and randomised clinical trials that compared marginal bone loss and failure rates between smokers and non-smokers. Implant failure was considered as total loss of the implant. Studies with patients who had periodontal disease prior to treatment or who had metabolic diseases were excluded. Two reviewers were involved in the research and screening process and disagreements were resolved by discussion. The quality of the studies was analysed using the Newcastle-Ottawa scale for non-randomised clinical trials. Data extracted from the studies included, when available: follow up period, number of subjects, smoking status, number of implants placed, implant system, implant length and diameter, healing period, antibiotics and mouth-rinse use, marginal bone loss, failure rate and drop-outs. For binary outcomes (implant failure) the estimate of the intervention effect was expressed in the form of an odds ratio (OR) with the confidence interval (CI) of 95%. For continuous outcomes (marginal bone loss) the average and standard deviation (SD) were used to calculate the standardised mean difference with a 95% CI. Meta-analysis was performed for studies with similar outcomes, I(2) a statistical test was used to express the heterogeneity among the studies. Publication bias was explored as well. A total of 15 observational studies were included in the review. The number of participants ranged from 60 to 1727 and the average age was 52.5 years. The follow-up period ranged from eight to 240 months. The total number of implants placed was 5840 in smokers and 14,683 in non-smokers. The Branemak system, (Noble Biocare AB, Goteborg, Sweden), was the most commonly used implant system. There was a statistically significant

  13. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals.

    Science.gov (United States)

    Strause, L; Saltman, P; Smith, K T; Bracker, M; Andon, M B

    1994-07-01

    The effects of calcium supplementation (as calcium citrate malate, 1000 mg elemental Ca/d) with and without the addition of zinc (15.0 mg/d), manganese (5.0 mg/d) and copper (2.5 mg/d) on spinal bone loss (L2-L4 vertebrae) was evaluated in healthy older postmenopausal women (n = 59, mean age 66 y) in a 2-y, double-blind, placebo-controlled trial. Changes (mean +/- SEM) in bone density were -3.53 +/- 1.24% (placebo), -1.89 +/- 1.40% (trace minerals only), -1.25 +/- 1.46% (calcium only) and 1.48 +/- 1.40% (calcium plus trace minerals). Bone loss relative to base-line value was significant (P = 0.0061) in the placebo group but not in the groups receiving trace minerals alone, calcium alone, or calcium plus trace minerals. The only significant group difference occurred between the placebo group and the group receiving calcium plus trace minerals (P = 0.0099). These data suggest that bone loss in calcium-supplemented, older postmenopausal women can be further arrested by concomitant increases in trace mineral intake.

  14. Alveolar bone loss associated to periodontal disease in lead intoxicated rats under environmental hypoxia.

    Science.gov (United States)

    Terrizzi, Antonela R; Fernandez-Solari, Javier; Lee, Ching M; Bozzini, Clarisa; Mandalunis, Patricia M; Elverdin, Juan C; Conti, María Ines; Martínez, María Pilar

    2013-10-01

    Previously reported studies from this laboratory revealed that rats chronically intoxicated with lead (Pb) under hypoxic conditions (HX) impaired growth parameters and induced damages on femoral and mandibular bones predisposing to fractures. We also described periodontal inflammatory processes under such experimental conditions. Periodontitis is characterised by inflammation of supporting tissues of the teeth that result in alveolar bone loss. The existence of populations living at high altitudes and exposed to lead contamination aimed us to establish the macroscopic, biochemical and histological parameters consistent with a periodontal disease in the same rat model with or without experimental periodontitis (EP). Sixty female rats were divided into: Control; Pb (1000ppm of lead acetate in drinking water); HX (506mbar) and PbHX (both treatments simultaneously). EP was induced by placing ligatures around the molars of half of the rats during the 14 days previous to the autopsy. Hemi-mandibles were extracted to evaluate bone loss by histomorphometrical techniques. TNFα plasmatic concentration was greater (plead intoxication under hypoxic environment enhanced not only alveolar bone loss but also systemic and oral tissues inflammatory parameters, which could aggravate the physiopathological alterations produced by periodontal disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Protective effect of low-dose risedronate against osteocyte apoptosis and bone loss in ovariectomized rats.

    Directory of Open Access Journals (Sweden)

    Tingjun Ye

    Full Text Available Osteocyte apoptosis is the first reaction to estrogen depletion, thereby stimulating osteoclastic bone resorption resulting in bone loss. We investigated the effects of two different risedronate (RIS doses (high and low on osteocyte apoptosis, osteoclast activity and bone loss in ovariectomized rats. Forty rats with ovariectomy (OVX and sham ovariectomy (SHAM were divided into 4 groups: 1 SHAM rats treated with saline (SHAM; 2 OVX rats treated with saline (OVX; 3 OVX rats treated with low-dose RIS (OVX-LR, 0.08 μg/kg/day; 4 OVX rats treated with high-dose RIS (OVX-HR, 0.8 μg/kg/day. All animals were sacrificed 90 days after surgery for the examinations of osteocyte apoptosis by caspase-3 staining, osteoclast activity by TRAP staining and bone volume by micro-CT scanning in lumbar vertebral cancellous bone. Both low and high dose RIS significantly reduced caspase-3 positive osteocytes, empty lacunae and TRAP positive osteoclasts in OVX rats. Although the difference in caspase-3 positive osteocytes was not significant between the OVX-LR and OVX-HR groups, numerically these cells were significantly more prevalent in OVX-HR (not OVX-LR group than in SHAM group. TRAP positive osteoclasts were significantly higher in OVX-LR group than in SHAM or OVX-HR group. There was no significant difference in bone volume among the OVX-LR, OVX-HR and SHAM groups, but lower in OVX group alone. However, significant increase in trabecular thickness only occurred in OVX-LR group. We conclude that both low and high dose RIS significantly inhibit osteocyte apoptosis and osteoclast activity in OVX rats, but the low-dose RIS has weaker effect on osteoclast activity. However, low-dose RIS preserves cancellous bone mass and microarchitecture as well as high-dose RIS after estrogen depletion.

  16. Vertical fracture and marginal bone loss of internal-connection implants: a finite element analysis.

    Science.gov (United States)

    Jimbo, Ryo; Halldin, Anders; Janda, Martin; Wennerberg, Ann; Vandeweghe, Stefan

    2013-01-01

    Marginal bone loss around implants is of great concern, and its cause may be multifactorial. Recently, clinical cases presenting marginal bone loss, in most cases accompanied by vertical fracture of internal-connection implants in the buccolingual direction, have been reported, in which unfavorable stress distribution is one possible cause of marginal bone resorption. The purpose of the current study was to characterize this type of marginal bone loss and implant fracture by conducting a finite element analysis (FEA). Clinical and radiographic evaluations showed that the prostheses of all reported cases had implant-level setups and were directly screwed to the internal implants. Intriguingly, all vertical fractures reported were in the buccolingual direction. Therefore, to characterize the specific implant fractures, FEA was conducted with misfit models created for two different setups, abutment-level and implant-level, both with screw-retained prostheses. The models were subjected to initial misfits of 0 μm (representing perfect fit), 50 μm, 100 μm, 150 μm, or 200 μm, and vertical loading was then applied. FEA revealed that, for the implant-level setup, excessive stress at the neck of the implant gradually increased in the buccolingual direction as the misfit increased. This result was not seen for the abutment-level setup. A broad maximum stress distribution was evident for the implant-level setup but not for the abutment-level setup. Broad distribution of excessive stress in the FEA correlated to the clinical cases, and marginal bone loss in these cases may be associated with mechanical alterations. To avoid unnecessary complications, selection of an abutment-level setup is strongly suggested.

  17. Contemporary noise-induced hearing loss (NIHL) prevention.

    Science.gov (United States)

    Sułkowski, Wiesław; Owczarek, Kalina; Olszewski, Jurek

    2017-08-31

    Hearing impairment caused by noise, traditionally called - depending on the duration of exposure - acute or chronic acoustic trauma, includes, in addition to presbyacusis, the most common adult population of hearing impaired. In Poland - according to the report of the Central Statistical Office (GUS, 2011), the number of workers employed in NDN exceeded the noise level (85 dB) is about 200 thousand, the highest in the mining, metal and metal products production, textiles and wood production. According to the Regulation of the Council of Ministers of on June 30, 2009, on the list of occupational diseases (Journal of Laws No. 132, item 1115), it is defined as "bilateral permanent hearing loss of the cochlear or sensory-nerve type, expressed as an increase in hearing threshold of at least 45 dB in the ear better heard, calculated as an arithmetic mean for frequencies 1,2 and 3 kHz. Hearing impairments also occur in the military and police during field training and in combat where the source of acoustic injuries are firearms and pulse-inducing explosions (as in some industries) with high C peak levels (Lc peak) Time to rise to a maximum of <1 ms. The prevalence of loud music listening, particularly by personal stereo players, is also affecting children and adolescents with audiometric hearing loss, according to the World Health Organization (WHO) estimates of around 15-20%. The preventive action strategy is defined by the European Union legislation and the national implementing legislation that reduces or eliminates the risk and reduces (if not eliminated), taking into account available technical and organizational solutions to minimize the risk of hearing damage. If you can not reduce the noise levels with technical and organizational methods, you need individual hearing protectors. Ear protectors may be equipped with electronic systems with active noise reduction (which can improve low and medium frequency performance), adjustable attenuation (improves speech

  18. Weight loss in the prevention and treatment of diabetes.

    Science.gov (United States)

    Delahanty, Linda M

    2017-11-01

    The American Diabetes Association nutrition and lifestyle recommendations for prediabetes and type 2 diabetes focus on losing 7% of body weight and increasing physical activity to at least 150minperweek. This emphasis is largely based on results of the Diabetes Prevention Program (DPP) and Look AHEAD (Action for Health in Diabetes) clinical trials. DPP demonstrated that a lifestyle intervention aimed at 7% weight loss and 150min of activity per week reduced diabetes incidence by 58% after 2.8years of follow-up and resulted in sustained improvements in hemoglobinA1c, blood pressure and lipid levels. After 15years of follow-up, DPP's lifestyle intervention sustained a 27% risk reduction in progression to diabetes. Look AHEAD's lifestyle intervention significantly reduced hemoglobinA1c, blood pressure, triglycerides, and the amount and costs of medications needed to treat these conditions when compared with diabetes support and education. Other clinical and psychological benefits achieved with lifestyle intervention were greater reductions in c-reactive protein, less self-reported retinopathy, reduced risk of nephropathy, less sexual dysfunction, decreased incidence of urinary incontinence and fatty liver, remission of sleep apnea, better physical functioning, less knee pain, more remission of diabetes, reduced incidence of depression, less body image dissatisfaction and improved quality-of-life. A number of DPP translation studies have demonstrated weight losses of 4 to 7% at 6month and 1year follow-up which has led to Medicare coverage for CDC recognized DPP lifestyle programs starting in April 2018. Translation studies of Look AHEAD using a variety of delivery formats are underway. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Cadmium-induced bone loss: Increased susceptibility in female beagles after ovariectomy

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, M.H.; Sacco-Gibson, N.A.; Peterson, D.P.

    1991-01-01

    Bone resorption, as measured by release of bone {sup 45}Ca, was significantly increased in elderly female beagles within 96 h of exposure to 15 mg/L Cd in drinking water. The {sup 45}Ca response was greater in ovariecotomized (OV) animals than in sham-operated (SO) controls and was not mediated by changes in calciotropic hormone concentrations. Mean blood Cd concentrations were 3--8 {mu}g/L during the earliest bone resorption response and 13--15 {mu}g/L at the end of the study. During 7 mo of Cd exposure, bone mineral densities decreased most in the OV animals exposed to Cd: {minus}15.4 {plus minus} 4.3% for the tibia distal end and {minus}7.2 {plus minus} 1.2% for the lumbar vertebrae (L2-L4) (mean {plus minus} SE, n=4). Results indicate that Cd may act directly on bone and that postmenopausal women exposed to Cd in industry or via cigarette smoke may be at increased risk of Cd-induced bone loss. 21 refs., 4 figs.

  20. A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

    DEFF Research Database (Denmark)

    Andreasen, Christina Møller; Ding, Ming; Overgaard, Søren

    2015-01-01

    Large animals as sheep are often used as models for human osteoporosis. Our aim was therefore to determine how glucocorticoid treatment of ovariectomised sheep affects the cancellous bone, determining the cellular events within the bone remodelling process that contributes to their bone loss...... in the mononuclear reversal cells colonising the surfaces. In conclusion, glucocorticoid treatment of ovariectomised sheep induced a significant bone loss, caused by an arrest of the reversal phase, resulting in an uncoupling of the bone formation and resorption during the reversal phase, as recently demonstrated....... Twenty female sheep were assigned for two groups; an untreated control group and an ovariectomised group treated with glucocorticoids (0.6mg/kg/day, 5 times weekly) for 7months. At 7months the glucocorticoid-treated ovariectomised sheep showed a significant change in the bone microstructure revealed...

  1. Retrospective analysis of survival rates and marginal bone loss on short implants in the mandible.

    Science.gov (United States)

    Draenert, Florian G; Sagheb, Keyvan; Baumgardt, Katharina; Kämmerer, Peer W

    2012-09-01

    Short implants have become an interesting alternative to bone augmentation in dental implantology. Design of shorter implants and longer surveillance times are a current research issue. The goal of this study was to show the survival rates of short implants below 9 mm in the partly edentulous mandibular premolar and molar regions with fixed prosthetics. Marginal vertical and 2D bone loss was evaluated additionally. Different implant designs are orientationally evaluated. A total of 247 dental implants with fixed prosthetics (crowns and bridges) in the premolar and molar region of the mandible were evaluated; 47 implants were 9 mm or shorter. Patient data were evaluated to acquire implant survival rates, implant diameter, gender and age. Panoramic X-rays were analysed for marginal bone loss. Average surveillance time was 1327 days. Cumulative survival rate (CSR) of short implants was 98% (1 implants lost) compared to 94% in the longer implants group without significance. Thirty-five of the short implants were Astratech (0 losses) and 12 were Camlog Screw Line Promote Plus (1 loss). Early vertical and two-dimensional marginal bone loss was not significantly different in short and regular length implant group with an average of 0.6 mm and 0.7 mm(2) in short implants over the observation period. Within the limitations of this study, we conclude that short implants with a length of 9 mm or less have equal survival rates compared with longer implants over the observation period of 1-3 years. © 2011 John Wiley & Sons A/S.

  2. Targeting the lateral but not the third ventricle induces bone loss in ewe: an experimental approach to generate an improved large animal model of osteoporosis.

    Science.gov (United States)

    Oheim, Ralf; Beil, Frank Timo; Barvencik, Florian; Egermann, Marcus; Amling, Michael; Clarke, Iain J; Pogoda, Pia

    2012-03-01

    Osteoporosis is a chronic disease characterized by bone loss and increased skeletal fragility. Large animal models are required for preclinical testing of new therapeutic approaches. We have recently demonstrated that continuous intracerebroventricular (ICV) application of leptin into the lateral ventricle (LV) induces bone loss in ewe. On the basis of these findings, we reasoned that the third ventricle (TV) is an even better target because of its closer location to the hypothalamus that mediates leptin effects on bone. Corriedale sheep were randomly mixed to four groups of four ewe each: control entire (control), ovarectomy plus ICV application of cerebrospinal fluid (OVX), OVX plus ICV application of leptin into the LV (leptin-LV); and ICV application of leptin into the TV (leptin-TV). After 3 months, histomorphometric characterization and bone turnover parameters were analyzed. Highly significant loss of trabecular bone was observed only in leptin-LV group. Increased osteoclast indices and urinary cross-lap excretion were observed in OVX and leptin-TV group. In contrast, serum parameters of osteoblast activity were only significantly decreased in leptin-LV group. Autopsy of ewe brain showed fibrosis around the stainless steel cannula in leptin-TV group. ICV application of leptin into the LV strongly reduces bone formation and leads to a highly significant trabecular bone loss in ewe. In contrast, ICV application of leptin into the TV is technically more demanding and results are unpredictable, because the required use of stainless steel cannula induces peri-implant fibrosis that might prevent leptin to enter the cerebrospinal fluid.

  3. Childhood Hearing Health: Educating for Prevention of Hearing Loss

    Directory of Open Access Journals (Sweden)

    Lacerda, Adriana Bender Moreira

    2014-09-01

    Full Text Available Introduction The presence of noise in our society has attracted the attention of health professionals, including speech-language pathologists, who have been charged along with educators with developing hearing conservation programs in schools. Objective To describe the results of three strategies for awareness and hearing preservation in first to fourth grades in public elementary schools. Methods The level of environmental noise in classrooms was assessed, and 638 elementary school students from first to fourth grades, 5 to 10 years of age, were audiologically evaluated. After the evaluations, educational activities were presented to children and educators. Results The noise level in the classroom ranged from 71.8 to 94.8 A-weighted decibels. The environment of the classroom was found to promote sound reverberation, which hinders communication. Thirty-two students (5.1% presented hearing alterations. Conclusion The application of strategies for a hearing conservation program at the school showed that noise is present in the room, and hearing loss, sometimes silent, affects schoolchildren. Students and teachers were aware that hearing problems can be prevented. Avoiding exposure to noise and improving the acoustics in classrooms are essential.

  4. Childhood Hearing Health: Educating for Prevention of Hearing Loss

    Science.gov (United States)

    Lacerda, Adriana Bender Moreira; Gonçalves, Claudia Giglio de Oliveira; Lacerda, Giselle; Lobato, Diolén Conceição Barros; Santos, Luciana; Moreira, Aline Carlezzo; Ribas, Angela

    2014-01-01

    Introduction The presence of noise in our society has attracted the attention of health professionals, including speech-language pathologists, who have been charged along with educators with developing hearing conservation programs in schools. Objective To describe the results of three strategies for awareness and hearing preservation in first to fourth grades in public elementary schools. Methods The level of environmental noise in classrooms was assessed, and 638 elementary school students from first to fourth grades, 5 to 10 years of age, were audiologically evaluated. After the evaluations, educational activities were presented to children and educators. Results The noise level in the classroom ranged from 71.8 to 94.8 A-weighted decibels. The environment of the classroom was found to promote sound reverberation, which hinders communication. Thirty-two students (5.1%) presented hearing alterations. Conclusion The application of strategies for a hearing conservation program at the school showed that noise is present in the room, and hearing loss, sometimes silent, affects schoolchildren. Students and teachers were aware that hearing problems can be prevented. Avoiding exposure to noise and improving the acoustics in classrooms are essential. PMID:25992146

  5. Monitoring of Bone Loss Biomarkers in Human Sweat: A Non-Invasive, Time Efficient Means of Monitoring Bone Resorption Markers under Micro and Partial Gravity Loading Conditions

    Data.gov (United States)

    National Aeronautics and Space Administration — The overall goal of this project was to validate the concept that the rate and extent of unloading-induced bone loss in humans can be assessed by monitoring the...

  6. Inadequate Loading Stimulus on ISS Results in Bone and Muscle Loss

    Science.gov (United States)

    Rice, A. J.; Genc, K. O.; Maender, C. C.; Gopalakrishnan, R.; Kuklis, M. M.; Cavanagh, P. R.

    2011-01-01

    INTRODUCTION Exercise has been the primary countermeasure to combat musculoskeletal changes during International Space Station (ISS) missions. However, these countermeasures have not been successful in preventing loss of bone mineral density (BMD) or muscle volume in crew members. METHODS We examined lower extremity loading during typical days on-orbit and on Earth for four ISS crew members. In-shoe forces were monitored using force-measuring insoles placed inside the shoes. BMD (by DXA), muscle volumes (by MRI), and strength were measured before and after long-duration spaceflight (181 +/- 15 days). RESULTS The peak forces measured during ISS activity were significantly less than those measured in 1g for the same activities. Typical single-leg loads on-orbit during walking and running were 0.89 +/- 0.17 body weights (BW) and 1.28 +/- 0.18 BW compared to 1.18 +/- 0.11 BW and 2.36 +/- .22 BW in 1g, respectively [2]. Crew members were only loaded for an average of 43.17 +/- 14.96 min a day while performing exercise on-orbit even though 146.8 min were assigned for exercise each day. Areal BMD decreased in the femoral neck and total hip by 0.71 +/- 0.34% and 0.81 +/- 0.21% per month, respectively. Changes in muscle volume were observed in the lower extremity (-10 to -16% calf; -4 to -7% thigh) but there were no changes in the upper extremity (+0.4 to -0.8%). Decrements in isometric and isokinetic strength at the knee (range: -10.4 to -24.1%), ankle (range: -4 to -22.3%), and elbow (range: -7.5 to - 16.7%) were also observed. Knee extension endurance tests showed an overall decline in total work (-14%) but an increased resistance to fatigue post-flight. DISCUSSION AND CONCLUSIONS Our findings support the conclusion that the measured exercise durations and/or loading stimuli were insufficient to protect bone and muscle health.

  7. The Role of Mechanical Stimulation in Recovery of Bone Loss-High versus Low Magnitude and Frequency of Force.

    Science.gov (United States)

    Nagaraja, Mamta Patel; Jo, Hanjoong

    2014-04-02

    Musculoskeletal pathologies associated with decreased bone mass, including osteoporosis and disuse-induced bone loss, affect millions of Americans annually. Microgravity-induced bone loss presents a similar concern for astronauts during space missions. Many pharmaceutical treatments have slowed osteoporosis, and recent data shows promise for countermeasures for bone loss observed in astronauts. Additionally, high magnitude and low frequency impact such as running has been recognized to increase bone and muscle mass under normal but not microgravity conditions. However, a low magnitude and high frequency (LMHF) mechanical load experienced in activities such as postural control, has also been shown to be anabolic to bone. While several clinical trials have demonstrated that LMHF mechanical loading normalizes bone loss in vivo, the target tissues and cells of the mechanical load and underlying mechanisms mediating the responses are unknown. In this review, we provide an overview of bone adaptation under a variety of loading profiles and the potential for a low magnitude loading as a way to counteract bone loss as experienced by astronauts.

  8. Severe Bone Loss as Part of the Life History Strategy of Bowhead Whales.

    Directory of Open Access Journals (Sweden)

    John C George

    Full Text Available The evolution of baleen constituted a major evolutionary change that made it possible for baleen whales to reach enormous body sizes while filter feeding on tiny organisms and migrating over tremendous distances. Bowhead whales (Balaena mysticetus live in the Arctic where the annual cycle of increasing and decreasing ice cover affects their habitat, prey, and migration. During the nursing period, bowheads grow rapidly; but between weaning and approximately year 5, bowhead whales display sustained baleen and head growth while limiting growth in the rest of their bodies. During this period, they withdraw resources from the skeleton, in particular the ribs, which may lose 40% of bone mass. Such dramatic changes in bones of immature mammals are rare, although fossil cetaceans between 40 and 50 million years ago show an array of rib specializations that include bone loss and are usually interpreted as related to buoyancy control.

  9. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Grubbe, M-C; Thomsen, Jesper Skovhus; Nyengaard, J R

    2014-01-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind...... limb. Sixty female Wistar rats, 14 weeks old, were divided into the following groups: baseline, controls, BTX, BTX+GH, and GH. GH was given at a dosage of 5 mg/kg/d for 4 weeks. Compared with controls, BTX resulted in lower periosteal bone formation rate (BFR/BS,-79%, Pbone mineral density (a......BMD, -13%, Pbone volume (BV/TV, -26%, Pbone strength (-12%, P

  10. Evaluation of pharmaceuticals with a novel 50-hour animal model of bone loss.

    Science.gov (United States)

    Tomimori, Yoshiya; Mori, Kaoru; Koide, Masanori; Nakamichi, Yuko; Ninomiya, Tadashi; Udagawa, Nobuyuki; Yasuda, Hisataka

    2009-07-01

    Osteoporosis remains a major public health problem through its associated fragility fractures. Several animal models for the study of osteoporotic bone loss, such as ovariectomy (OVX) and denervation, require surgical skills and several weeks to establish. Osteoclast differentiation and activation is mediated by RANKL. Here we report the establishment of a novel and rapid bone loss model by the administration of soluble RANKL (sRANKL) to mice. Mice were injected intraperitoneally with sRANKL and used to evaluate existing anti-osteoporosis drugs. sRANKL decreased BMD within 50 h in a dose-dependent manner. The marked decrease in femoral trabecular BMD shown by pQCT and the 3D images obtained by microCT were indistinguishable from those observed in the OVX model. Histomorphometry showed that osteoclastic activity was significantly increased in the sRANKL-injected mice. In addition, serum biochemical markers of bone turnover such as Ca, C-telopeptide of type 1 collagen (CTX), and TRACP5b were also significantly increased in the sRANKL-injected mice in a dose-dependent manner. Bisphosphonates (BPs), selective estrogen receptor modulators (SERMs), and PTH are commonly used for the treatment of osteoporosis. We successfully evaluated the effects of anti-bone-resorbing agents such as BPs, a SERM, and anti-RANKL-neutralizing antibody on bone resorption in a couple of weeks. We also evaluated the effects of PTH on bone formation in 2 wk. A combination of sRANKL injections and OVX made it possible to evaluate a SERM. The sRANKL model is the simplest, fastest, and easiest of all osteoporosis models and could be useful in the evaluation of drug candidates for osteoporosis.

  11. Increased risk for bone loss in women with systemic sclerosis: a comparative study with rheumatoid arthritis.

    Science.gov (United States)

    Kilic, Gamze; Kilic, Erkan; Akgul, Ozgur; Ozgocmen, Salih

    2016-04-01

    To assess bone mass in women with systemic sclerosis (SSc) in comparison to age and sex-matched patients with rheumatoid arthritis (RA), and to evaluate factors influencing bone mineral density (BMD). Patients were consecutively recruited and assessed for BMD at the lumbar spine and hip by dual-energy X-ray absorptiometry (DEXA) using a densitometer. In SSc, the extent of skin involvement, modified Rodnan skin thickness score (mRSS) and Medsger disease severity index were assessed. Forty-three patients with SSc and 38 age-matched patients with RA were included. There was no difference in BMD measurements between patients with diffuse or limited SSc. Patients with SSc had similar risk factors associated with osteoporosis (OP) or low bone mass except for low body mass index (BMI) and low vitamin D levels compared to patients with RA. Lumbar spinal BMD and T score were similar between groups. Total hip and femoral neck BMD and T score at femoral neck and total hip were significantly lower in patient with SSc versus RA. There was significant association between mRSS, Medsger severity score (peripheral vascular involvement and skin) and femoral BMD. There is an increased risk for bone loss in patients with SSc and the risk of OP is associated with disease severity, prolonged menopause and disease duration. The complex pathophysiology of bone metabolism as well as complex pathogenesis of the SSc pose some difficulty reaching clear-cut conclusions on the causal relationship between SSc and bone loss. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  12. Piperine inhibit inflammation, alveolar bone loss and collagen fibers breakdown in a rat periodontitis model.

    Science.gov (United States)

    Dong, Y; Huihui, Z; Li, C

    2015-12-01

    Piperine exhibits anti-inflammatory activity, and has a long history of medicinal use. The objective of this study was to investigate the protective effects of piperine on inflammation, alveolar bone and collagen fibers in experimental periodontitis. We evaluated the related expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-8 and MMP-13 to enhance insight into these effects. Thirty-two Wistar rats were divided into four groups of eight animals each: control group, periodontitis group, periodontitis plus 50 mg/kg piperine group and periodontitis plus 100 mg/kg piperine group. Histopathologic changes were detected by hematoxylin and eosin staining. Alveolar bone loss and trabecula microstructures were evaluated by micro-computed tomography. Changes in collagen fibers were assessed by picrosirius red staining. Western blot analysis was conducted to determine the levels of IL-1β, TNF-α, MMP-8 and MMP-13. Piperine clearly inhibited alveolar bone loss and reformed trabecula microstructures in a dose-dependent manner. Histological staining showed that piperine significantly reduced the infiltration of inflammation in soft tissues. Both doses of piperine limited the fractions of degraded areas in collagen fibers. Piperine (100 mg/kg) significantly downregulated the expressions of IL-1β, MMP-8 and MMP-13 in periodontitis, but not that of TNF-α. Piperine displays significantly protective effects on inflammation, alveolar bone loss, bone microstructures and collagen fiber degradation in experimental periodontitis. The effects may be ascribed to its inhibitory activity on the expressions of IL-1β, MMP-8 and MMP-13. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling

    Directory of Open Access Journals (Sweden)

    F.A. Pereira

    2007-04-01

    Full Text Available Data about the impact of bariatric surgery (BS and subsequent weight loss on bone are limited. The objective of the present study was to determine bone mineral density (BMD, bone remodeling metabolites and hormones that influence bone trophism in premenopausal women submitted to BS 9.8 months, on average, before the study (OGg, N = 16. The data were compared to those obtained for women of normal weight (CG, N = 11 and for obese women (OG, N = 12. Eight patients in each group were monitored for one year, with the determination of BMD, of serum calcium, phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D, insulin-like growth factor-I (IGF-I and osteocalcin, and of urinary calcium and deoxypyridinoline. The biochemical determinations were repeated every three months in the longitudinal study and BMD was measured at the end of the study. Parathyroid hormone levels were similar in the three groups. IGF-I levels (CG = 332 ± 62 vs OG = 230 ± 37 vs OGg = 128 ± 19 ng/mL were significantly lower in the operated patients compared to the non-operated obese women. Only OGg patients presented a significant fall in BMD of 6.2% at L1-L4, of 10.2% in the femoral neck, and of 5.1% in the forearm. These results suggest that the weight loss induced by BS is associated with a significant loss of bone mass even at sites that are not influenced by weight overload, with hormonal factors such as IGF-I being associated with this process.

  14. α₂-Antiplasmin is involved in bone loss induced by ovariectomy in mice.

    Science.gov (United States)

    Shiomi, Akihito; Kawao, Naoyuki; Yano, Masato; Okada, Kiyotaka; Tamura, Yukinori; Okumoto, Katsumi; Matsuo, Osamu; Akagi, Masao; Kaji, Hiroshi

    2015-10-01

    The mechanism of postmenopausal osteoporosis is not fully understood. α2-Antiplasmin (α2-AP) is the primary inhibitor of plasmin in the fibrinolytic system, but is known to have activities beyond fibrinolysis. However, its role in bone metabolism and the pathogenesis of osteoporosis remains unknown. In the current study, we therefore examined the effects of α2-AP deficiency on ovariectomy (OVX)-induced bone loss by using wild-type and α2-AP-deficient mice. Quantitative computed tomography analysis revealed that α2-AP deficiency blunted OVX-induced trabecular bone loss in mice. Moreover, α2-AP deficiency significantly blunted serum levels of bone-specific alkaline phosphatase, cross-linked C-telopeptide of type I collagen, and interleukin (IL)-1β elevated by OVX. α2-AP treatment elevated the levels of IL-1β and tumor necrosis factor (TNF)-α mRNA in RAW 264.7 cells, although it suppressed osteoclast formation induced by receptor activator of nuclear factor-κB ligand. α2-AP treatment activated ERK1/2 and p38 MAP kinase pathways in RAW 264.7 cells, and these MAP kinase inhibitors antagonized the levels of IL-1β mRNA elevated by α2-AP. The data demonstrate that α2-AP is linked to bone loss due to OVX, through a mechanism that depends in part on the production of IL-1β and TNF-α in monocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Crestal bone loss and periimplant inflammatory parameters around zirconia implants: A systematic review.

    Science.gov (United States)

    Vohra, Fahim; Al-Kheraif, Abdul Aziz; Ab Ghani, Siti Mariam; Abu Hassan, Mohamed Ibrahim; Alnassar, Talal; Javed, Fawad

    2015-09-01

    Zirconia implants have been used for oral rehabilitation; however, evidence of their ability to maintain crestal bone and periimplant soft tissue health is not clear. The purpose of this systematic review was to evaluate crestal bone loss (CBL) around zirconia dental implants and clinical periimplant inflammatory parameters. The focus question addressed was, "Do zirconia implants maintain crestal bone levels and periimplant soft tissue health?" Databases were searched for articles from 1977 through September 2014 with different combinations of the following MeSH terms: "dental implants," "zirconium," "alveolar bone loss," "periodontal attachment loss," "periodontal pocket," "periodontal index." Letters to the editor, case reports, commentaries, review articles, and articles published in languages other than English were excluded. Thirteen clinical studies were included. In 8 of the studies, the CBL around zirconia implants was comparable between baseline and follow-up. In the other 5 studies, the CBL around zirconia implants was significantly higher at follow-up. Among the studies that used titanium implants as controls, 2 studies showed significantly higher CBL around zirconia implants, and in 1 study, the CBL around zirconia and titanium implants was comparable. The reported implant survival rates for zirconia implants ranged between 67.6% and 100%. Eleven studies selectively reported the periimplant inflammatory parameters. Because of the variations in study design and methodology, it was difficult to reach a consensus regarding the efficacy of zirconia implants in maintaining crestal bone levels and periimplant soft tissue health. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  16. Pyogenic granuloma associated with periodontal abscess and bone loss - A rare case report

    Directory of Open Access Journals (Sweden)

    Bhrugesh J Panseriya

    2011-01-01

    Full Text Available A diverse group of the pathologic process can produce the enlargement of soft tissues in the oral cavity and often present a diagnostic challenge. This soft tissue enlargement may represent a variation of the normal anatomic structure, inflammatory reaction, cyst, neoplasm, and developmental anomalies. A group of reactive hyperplasias, which develop in response to chronic recurring tissue injury that stimulates an excessive tissue repair response. The pyogenic granuloma (PG is a reactive enlargement that is an inflammatory response to local irritation such as calculus, a fractured tooth, rough dental restoration, and foreign materials or hormonal (pregnancy tumor and rarely associated with bone loss. This paper presents a rare case of PG associated with periodontal abscess and bone loss in a 30-year-old male.

  17. Bone Loss in the Acute Stage Following Burn Injury - Original Investigation

    Directory of Open Access Journals (Sweden)

    Berrin Leblebici

    2007-06-01

    Full Text Available Aim: The purpose of this study was to determine whether a bone loss occurs during acute period following burn injury or not, and to investigate the effects of various parameters on it. Materials and Methods: This study was conducted on 19 patients, ages between 20 and 50, who had a burn injury with more than %20 of Total Body Surface Area (TBSA. We recorded the patients’ burn cause, localization, percantage, ambulation and functional status. At the end of the first month, we measured bone mıneral densıty of total L1-L4 vertebrae, left distal forearm, left total femur, in all patients. A Z score less than –1 was accepted to be the indicator of bone loss. Results: The mean age of the patients (14 male and 5 female was 33.09±11.61. We found a Z score less then -1 in 68.4% of left distal forearm, 21.1% of left total femur and 36.8% of total L1-L4 vertabrae measurements. There were no significant correlations between TBSA, Functional Ambulatıon Scale and Functional Independence Measure, and Z scores. Conclusion: There is a reduction in Bone Mineral Density in patıents wıth moderate/severe burn ınjuries in the acute period which is not correlated wıth neither TBSA nor functional status. (From the World of Osteoporosis 2007;13:33-6

  18. Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long-Duration Space Flight

    Science.gov (United States)

    Sibonga, Jean; Amin, Shreyasee

    2010-01-01

    AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk. compare data from crew members ("observed") with what would be "expected" from Rochester Bone Health Study. AIM 2: To provide a summary of current evidence available on potential risk factors for bone loss, recovery & fracture following long-duration space flight. integrative review of all data pre, in-, and post-flight across disciplines (cardiovascular, nutrition, muscle, etc.) and their relation to bone loss and recovery

  19. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

    Science.gov (United States)

    2013-09-01

    Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT : Bone loss that results from age- related and post- menopausal osteoporosis , and...5 References……………………………………………………………………………. 10 4 Introduction Osteoporosis , both age- related and post- menopausal ...a novel and highly innovative therapeutic approach to age- related osteoporosis . Body On July 27, 2012 we requested a 6 month extension without

  20. Evaluation of the Survival Rate and Bone Loss of Implants with Various Lengths

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    AR. Rokn

    2006-12-01

    Full Text Available Statement of Problem: The replacement of missing teeth with implant-associated restorations has become a widely used treatment modality in recent years. The length of dental implants may be a critical factor in achieving and maintaining osseointegration.Purpose: The aim of this study was to evaluate the survival rate and bone loss of dental implants with different lengthsMaterials and Methods: A retrospective cohort study was performed on 60 ITI-system implants, evenly distributed into three groups including 8, 10 and 12 mm high implants in the posterior segments of both jaws. Demographic information, oral hygiene,cigarette smoking, implant length, duration of implant placement (at least 24 months,bleeding on probing index and pocket probing depth were recorded for all participants.Bone loss was calculated using pre- and post-operative panoramic radiographs.Results: The mean rate of bone loss was different among the three groups and were found to be 0.21 (0.45, 0.3 (0.41 and 0.43 (0.55 mm in the 8, 10, and 12 mm high implants, respectively. Neither mean bone loss nor bleeding on probing index showed significant differences with implant length. A significant correlation was found between implant length and pocket probing depth (P<0.0001.Conclusion: The results of this study suggest that both short (8 mm high and long (10 or 12 mm high implants may be used with nearly equal success rates in the posterior segments of the jaws.

  1. Impact of cannabis sativa (marijuana) smoke on alveolar bone loss: a histometric study in rats.

    Science.gov (United States)

    Nogueira-Filho, Getulio R; Todescan, Sylvia; Shah, Adnan; Rosa, Bruno T; Tunes, Urbino da R; Cesar Neto, Joao B

    2011-11-01

    Cannabis sativa (marijuana) can interfere with bone physiopathology because of its effect on osteoblast and osteoclast activity. However, its impact on periodontal tissues is still controversial. The present study evaluates whether marijuana smoke affects bone loss (BL) on ligature-induced periodontitis in rats. Thirty male Wistar rats were used in the study. A ligature was placed around one of the mandible first molars (ligated teeth) of each animal, and they were then randomly assigned to one of two groups: control (n = 15) or marijuana smoke inhalation ([MSI] for 8 minutes per day; n = 15). Urine samples were obtained to detect the presence of tetrahydrocannabinol. After 30 days, the animals were sacrificed and decalcified sections of the furcation area were obtained and evaluated according to the following histometric parameters: bone area (BA), bone density (BD), and BL. Tetrahydrocannabinol was positive in urine samples only for the rats of the MSI group. Non-significant differences were observed for unligated teeth from both groups regarding BL, BA, and BD (P >0.05). However, intragroup analysis showed that all ligated teeth presented BL and a lower BA and BD compared to unligated teeth (P <0.05). The intergroup evaluation of the ligated teeth showed that the MSI group presented higher BL and lower BD (P <0.05) compared to ligated teeth from the control group. Considering the limitations of this animal study, cannabis smoke may impact alveolar bone by increasing BL resulting from ligature-induced periodontitis.

  2. Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

    Science.gov (United States)

    Reumann, Marie K; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Stephen B; Lukashova, Lyudmila; Boskey, Adele L; Mayer-Kuckuk, Philipp

    2011-10-01

    Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Reduction of Dietary Acid Load as a Potential Countermeasure for Bone Loss Associated with Spaceflight

    Science.gov (United States)

    Zwart, S. R.; Watts, S. M.; Sams, C. F.; Whitson, P. A.; Smith, S. M.

    2006-01-01

    In several studies we tested the concepts that diet can alter acid-base balance and that reducing the dietary acid load has a positive effect on maintenance of bone. In study 1, (n = 11, 60-90 d bed rest), the renal acid load of the diet was estimated from its chemical composition, and was positively correlated with urinary markers of bone resorption (P less than 0.05); that is, the greater the acid load, the greater the excretion of bone resorption markers. In study 2, in males (n = 8, 30 d bed rest), an estimate of the ratio of nonvolatile acid precursors to base precursors in the diet was positively correlated (P less than 0.05) with markers of bone resorption. In study 3, for 28 d subjects received either a placebo (n = 6) or an essential amino acid supplement (n = 7) that included methionine, a known acid precursor. During bed rest (28 d), urinary calcium was greater than baseline levels in the supplemented group but not the control group (P less than 0.05), and in the supplemented group, urinary pH decreased (P less than 0.05). In study 4, less bone resorption occurred in space crew members who received potassium citrate (n = 6) during spaceflight of 4-6 months than in crew members who received placebo or were not in the study (n = 8) (P less than 0.05). Reducing acid load has the potential to mitigate increased bone resorption during spaceflight, and may serve as a bone loss countermeasure.

  4. Bone loss at implants and teeth in the same segment of the dentition in partially dentate subjects.

    Science.gov (United States)

    Cecchinato, Denis; Marino, Massimiliano; Lindhe, Jan

    2017-05-01

    Some studies have indicated that marginal bone loss at implants and at teeth are similar, while results from other studies showed that implants lost more bone than teeth in the same dentition. To determine the amount of progressive marginal bone loss that had occurred at implants and teeth in the same segment of the dentition following implant placement in partially dentate subjects. A total of 217 patients with a total of 573 implants and 318 teeth present in the same segments of the dentition were included. Radiographs were available from 1 year (baseline) and ≥3 years after loading. The mean bone loss that occurred between the two examinations was at implants 0.42 ± 0.68 mm and at teeth 0.44 ± 0.52 mm. Thirty-eight subjects (18%) had ≥1 implant exhibiting >1 mm bone loss. Bone loss at the 148 implants in this category of patients was 1.30 ± 1.04 mm with a corresponding loss at the 69 teeth of 0.53 ± 0.62 mm. Eighteen subjects (8%) had ≥1 tooth that exhibited >1 mm bone loss. The mean amount of bone loss in this sample was 1.37 ± 0.87 mm (38 teeth) and 0.29 ± 0.31 mm (56 implants). This study showed that marginal bone loss at implants and teeth in many partially dentate subjects might be independent phenomena. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Effects of Weight Loss on Lean Mass, Strength, Bone, and Aerobic Capacity.

    Science.gov (United States)

    Weiss, Edward P; Jordan, Richard C; Frese, Ethel M; Albert, Stewart G; Villareal, Dennis T

    2017-01-01

    This study aimed to evaluate the hypothesis that exercise attenuates the reductions in lean mass, muscle strength, bone mineral density, and V˙O2max that accompany modest weight loss induced by calorie restriction (CR). Overweight, sedentary women and men (n = 52, 45-65 yr) were randomized to 6%-8% weight loss by using CR, endurance exercise training (EX), or both (CREX). The CR and the CREX groups underwent counseling to reduce energy intake by 20% and 10%, respectively. The EX and the CREX groups exercised 7.4 ± 0.5 and 4.4 ± 0.5 h·wk, respectively. Before and after 16.8 ± 1.1 wk of weight loss, lean mass and bone mineral density were measured with dual-energy x-ray absorptiometry, strength was measured with dynamometry, and aerobic capacity (V˙O2max) was measured with indirect calorimetry during maximal-intensity treadmill exercise. Weight loss was ~7% in all groups. Decreases in whole-body (~2%, P = 0.003) and lower extremity (~4%, P weight loss, these reductions were attenuated in the CREX group (~1%, P = 0.44 and ~2%, P = 0.05, respectively) and absent in the EX group. Absolute aerobic capacity decreased ~6% in the CR group (P = 0.04), was unchanged in the CREX group (P = 0.28), and increased ~15% in the EX group (P weight loss (~7%) induced by 20% CR in overweight women and men decreases lean mass and reduces absolute V˙O2max. Exercise protects against these effects. Although the CR-induced changes might be considered physiologically appropriate for a reduced body weight, exercise preserves and/or improves these parameters during weight loss, which likely improves physical function. These findings support the notion of using exercise as an important component of weight loss programs.

  6. Management of severe periacetabular bone loss combined with pelvic discontinuity in revision hip arthroplasty.

    Science.gov (United States)

    Friedrich, Max J; Schmolders, Jan; Michel, Robert D; Randau, Thomas M; Wimmer, Matthias D; Kohlhof, Hendrik; Wirtz, Dieter C; Gravius, Sascha

    2014-12-01

    Revision of failed total hip arthroplasty with massive acetabular bone loss resulting in pelvic discontinuity represents a rare but challenging problem. The objective of this study was to present short to mid-term results of revision total hip arthroplasty with a custom-made acetabular implant in a consecutive series of patients with pelvic discontinuity. We retrospectively reviewed 18 consecutive patients with massive acetabular bone loss (Paprosky Type 3B) resulting in pelvic discontinuity reconstructed with revision total hip arthroplasty using a custom-made acetabular component. The prosthesis was created on the basis of a thin-cut 1-mm computed tomography (CT) scan of the pelvis. Initial stability of the implant was obtained by screw fixation. Harris hip score and sequential radiographs were used to evaluate the clinical and radiographic results. At an average follow up of 30 months (range 17-62 months) 16 of 18 (88.9%) custom-made implants were considered radiographically stable without signs of acetabular migration of more than 2 mm in the horizontal or vertical direction, implant rotation or screw breakage. Complications included two periprosthetic joint infections treated with explantation of the implant. Three patients had recurrent dislocations postoperatively. The mean Harris hip score improved from 28 ± 12 points preoperatively to 69 ± 13 points at the time of last follow up. Treatment of acetabular bone loss and pelvic discontinuity with a custom-made acetabular component can provide a durable solution with good clinical and radiographic results.

  7. 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.

  8. 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.

  9. Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside—a Comprehensive Review

    NARCIS (Netherlands)

    C.H. Alves (Celso Henrique); E. Farrell (Eric); M. Vis (M.); E.M. Colin (Edgar); E.W. Lubberts (Erik)

    2016-01-01

    textabstractThroughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast

  10. 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...... activity at the time of investigation. By contrast, BMDARM was decreased in patients with active disease. BMD in any of the three measured locations was not directly correlated to duration of the disease. However, the bone mass in the appendicular skeleton was already decreased within the first two years...... to clinical improvement, which may counteract the expected negative effect of these drugs on bone in rheumatoid arthritis....

  11. Dietary Supplement Attenuates Radiation-Induced Osteoclastogenic and Oxidative Stress-Related Responses and Protects Adult Mice from Radiation-Induced Bone Loss

    Science.gov (United States)

    Globus, Ruth; Schreurs, Ann-Sofie; Tahimic, Candice; Shirazi-Fard, Yasaman; Alwood, Joshua; Shahnazari, Mohammed; Halloran, Bernard

    2015-01-01

    Our central hypothesis is that oxidative stress plays a key role in cell dysfunction and progressive bone loss caused by radiation exposure during spaceflight. In animal studies, excess free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. We previously reported that exposure to low or high-LET radiation rapidly increases expression levels of pro-osteoclastogenic and oxidative stress-related genes in bone and marrow, followed by pathological changes in skeletal structure. To screen various antioxidants for radioprotective effects on bone, 4 month old, male C57Bl6/J mice were treated with a dietary antioxidant cocktail, injectable alpha-lipoic acid, or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs total body radiation and one day later marrow cells were collected and the relevant genes analyzed for expression levels. Of the candidates tested, DP was most effective in reducing bone resorption-related gene expression. Microcomputed tomography revealed that DP also prevented the radiation-induced deterioration of skeletal microarchitecture, as indicated by percent bone volume, trabecular spacing and trabecular number. DP had similar protective effects on skeletal structure after sequential exposure to protons (0.5 Gy, 150MeV/n) and 56Fe 0.5Gy, 600 MeV/n). When cultured ex vivo under osteogenic conditions, bone marrow-derived cells from DP-fed animals exhibited increased colony numbers compared to control diet-fed animals. These findings suggest that DP exerted pro-osteogenic effects apart from previously identified anti-resorptive actions, which may contribute to radioprotection of skeletal tissue. In conclusion, a diet enriched in certain types of antioxidants and polyphenols such as DP may be useful as an intervention to protect tissues from degenerative effects of ionizing radiation.

  12. Frequent complications and severe bone loss associated with the repiphysis expandable distal femoral prosthesis.

    Science.gov (United States)

    Cipriano, Cara A; Gruzinova, Irina S; Frank, Rachel M; Gitelis, Steven; Virkus, Walter W

    2015-03-01

    The treatment of choice for distal femur malignancies in skeletally immature patients remains controversial. An expandable endoprosthesis device (Repiphysis Limb Salvage System; Wright Medical Technology, Arlington, TN, USA) allows for limb preservation and noninvasive lengthening but has been associated with significant complications; however, the extent and implications of bone loss associated with this implant have not been reported. Our goals were to report (1) the 2-year minimum clinical outcomes after placement of the Repiphysis expandable prosthesis for pediatric distal femur malignancies; (2) the complications associated with this prosthesis; (3) the failure rate of this prosthesis; and (4) the revision alternatives available for salvage procedures. Between 2002 and 2010, one surgeon (SG) treated all skeletally immature patients (mean age, 10.1 years; range, 4.7-13.6 years) with distal femoral osteosarcoma using a Repiphysis expandable prosthesis. Of the 12 patients who met these criteria, two were excluded for death from disease before 2 years, and mean followup for the remaining 10 was 72 months (range, 26-119 months). Medical records were retrospectively reviewed for complications and clinical outcomes, as assessed by the Musculoskeletal Tumor Society (MSTS) scoring system. Radiographs at final followup were reviewed for bone loss and analyzed by the two senior authors (SG, WWV) to determine reconstruction options available for future revisions. MSTS scores averaged 67%, and we observed 37 implant-related complications requiring a total of 15 reoperations. Six patients underwent implant revisions with aseptic loosening being the predominant mode of failure; ultimately, four of these were converted to adult modular oncology prostheses, and two underwent total femoral replacements. Bone loss in this series was severe in terms of femoral length, cortical thinning, and metadiaphyseal compromise, and most patients will not have sufficient bone stock to permit

  13. Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene.

    Science.gov (United States)

    Shukla, Priyanka; Mansoori, Mohd Nizam; Kakaji, Manisha; Shukla, Manoj; Gupta, Sushil Kumar; Singh, Divya

    2017-03-17

    A growing understanding of the bone remodeling process suggests that inflammation significantly contributes to the pathogenesis of osteoporosis. T cells and various cytokines contribute majorly to the estrogen deficiency-induced bone loss. Recent studies have identified the IL-12 cytokine family as consisting of pro-inflammatory IL-12 and IL-23 and the anti-inflammatory IL-27 and IL-35 cytokines. IL-27 exerts protective effects in autoimmune diseases like experimental autoimmune encephalomyelitis; however, its role in the pathogenesis of osteoporosis remains to be determined. In this report, we study the effect of IL-27 supplementation on ovariectomized estrogen-deficient mice on various immune and skeletal parameters. IL-27 treatment in ovariectomized mice suppressed Th17 cell differentiation by inhibiting transcription factor RORγt. Supplementation of IL-27 activates Egr-2 to induce IL-10 producing Tr1 cells. IL-27 treatment prevented the loss of trabecular micro-architecture and preserved cortical bone parameters. IL-27 also inhibited osteoblast apoptosis through increased Egr-2 expression, which induces anti-apoptotic factors like MCL-1. IL-27 suppressed osteoclastogenesis in an Egr-2-dependent manner that up-regulates Id2, the repressor of the receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis. Additionally, these results were corroborated in female osteoporotic subjects where we found decreased serum IL-27 levels along with reduced Egr-2 expression. Our study forms a strong basis for using humanized IL-27 toward the treatment of post-menopausal osteoporosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Deer bone extract prevents against scopolamine-induced memory impairment in mice.

    Science.gov (United States)

    Du, Chun Nan; Min, A Young; Kim, Hyun Jeong; Shin, Suk Kyung; Yu, Ha Ni; Sohn, Eun Jeong; Ahn, Chang-Won; Jung, Sung Ug; Park, Soo-Hyun; Kim, Mee Ree

    2015-02-01

    Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aβ1-42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine.

  15. Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Raul Hernandes Bortolin

    Full Text Available Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM, and T1DM plus zinc supplementation (T1DMS. Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young's modulus, and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic

  16. Metaphyseal and diaphyseal bone loss in the tibia following transient muscle paralysis are spatiotemporally distinct resorption events.

    Science.gov (United States)

    Ausk, Brandon J; Huber, Philippe; Srinivasan, Sundar; Bain, Steven D; Kwon, Ronald Y; McNamara, Erin A; Poliachik, Sandra L; Sybrowsky, Christian L; Gross, Ted S

    2013-12-01

    When the skeleton is catabolically challenged, there is great variability in the timing and extent of bone resorption observed at cancellous and cortical bone sites. It remains unclear whether this resorptive heterogeneity, which is often evident within a single bone, arises from increased permissiveness of specific sites to bone resorption or localized resorptive events of varied robustness. To explore this question, we used the mouse model of calf paralysis induced bone loss, which results in metaphyseal and diaphyseal bone resorption of different timing and magnitude. Given this phenotypic pattern of resorption, we hypothesized that bone loss in the proximal tibia metaphysis and diaphysis occurs through resorption events that are spatially and temporally distinct. To test this hypothesis, we undertook three complimentary in vivo/μCT imaging studies. Specifically, we defined spatiotemporal variations in endocortical bone resorption during the 3weeks following calf paralysis, applied a novel image registration approach to determine the location where bone resorption initiates within the proximal tibia metaphysis, and explored the role of varied basal osteoclast activity on the magnitude of bone loss initiation in the metaphysis using μCT based bone resorption parameters. A differential response of metaphyseal and diaphyseal bone resorption was observed throughout each study. Acute endocortical bone loss following muscle paralysis occurred almost exclusively within the metaphyseal compartment (96.5% of total endocortical bone loss within 6days). Using our trabecular image registration approach, we further resolved the initiation of metaphyseal bone loss to a focused region of significant basal osteoclast function (0.03mm(3)) adjacent to the growth plate. This correlative observation of paralysis induced bone loss mediated by basal growth plate cell dynamics was supported by the acute metaphyseal osteoclastic response of 5-week vs. 13-month-old mice. Specifically

  17. Racial differences in bone loss and relation to menopause among HIV-infected and uninfected women.

    Science.gov (United States)

    Sharma, Anjali; Flom, Peter L; Rosen, Clifford J; Schoenbaum, Ellie E

    2015-08-01

    To characterize changes in bone mineral density (BMD) according to race among HIV-infected and uninfected women, and to evaluate the relationship between race and menopause-related bone loss. Dual X-ray absorptiometry measured BMD on study entry and a minimum of 18 months later in 246 HIV-infected and 219 HIV-uninfected women in the Menopause Study. Linear regression analyses determined percent annual BMD change at the total hip (TH), femoral neck (FN), and lumbar spine (LS) after adjusting for potential confounders. Race-stratified and HIV-infected subgroup analyses were performed. At baseline, mean age was 45 years, 19% of women were postmenopausal. HIV-infected women were more likely to be black (58% vs. 38%), and had lower BMI and less cigarette exposure when compared to HIV-uninfected women. Women who were perimenopausal at baseline and postmenopausal at follow-up had the greatest TH bone loss (-1.68%/yr, p change at the FN and TH. In race-stratified analyses, HIV infection was associated with TH BMD loss in non-black women. Black women experienced greater menopause-associated decline in TH BMD compared with non-black women. The association of HIV and BMD differs strikingly by race, as do the effects of the menopausal transition on bone. Determining the extent to which the effect of HIV on fracture risk varies by race will be crucial to identify HIV-infected women at greatest risk for osteoporotic fracture, particularly as they enter menopause. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The efficiency of voluntary incentive policies for preventing biodiversity loss

    Science.gov (United States)

    David J. Lewis; Andrew J. Plantinga; Erik Nelson; Stephen. Polasky

    2011-01-01

    Habitat loss is a primary cause of loss of biodiversity but conserving habitat for species presents challenges. Land parcels differ in their ability to produce returns for landowners and landowners may have private information about the value of the land to them. Land parcels also differ in the type and quality of habitat and the spatial pattern of land use across...

  19. Is there loss of vibration amplitude across the snap coupling of the bone-anchored hearing aid?

    Science.gov (United States)

    Majdalawieh, Osama; Van Wijhe, Rene G; Bance, Manohar

    2006-04-01

    There is loss of vibration transmission across the snap coupling connecting the Bone-Anchored Hearing Aid transducer to the implanted abutment on the head. The only nonrigid part of the Bone-Anchored Hearing Aid system is the connection between the output of the transducer and the abutment. Vibration losses across the coupling have not been previously measured. If a loss is found, a change in design could improve the efficiency of the Bone-Anchored Hearing Aid. This would be very helpful in borderline cases in which the Bone-Anchored Hearing Aid does not have enough power to achieve adequate hearing threshold levels. A laser Doppler vibrometer was used to measure vibrations on the output stem and four points on the abutment of the Bone-Anchored Hearing Aid. The Bone-Anchored Hearing Aid was coupled to a dry skull through a plexiglas bite bar screwed to the skull. The impedance load was varied by fixing the skull. A control loose coupling was measured. Five Bone-Anchored Hearing Aid Compacts were measured. There was little loss across the Bone-Anchored Hearing Aid snap coupling. At frequencies above 500 Hz, there was no more than 5-dB loss at any frequency. Changing the impedance load by fixing the skull did not change the loss across the coupling. The snap coupling is an efficient means of transmitting vibrations to the skull. There is little loss of vibration attenuation across it. Increases in functional Bone-Anchored Hearing Aid amplification gain cannot be achieved by further optimizing this interface.

  20. A comparison of the reliability and validity of bone stock loss classification systems used for revision hip surgery.

    Science.gov (United States)

    Gozzard, Charles; Blom, Ashley; Taylor, A; Smith, Evert; Learmonth, Ian

    2003-08-01

    Three femoral (Paprosky, American Academy of Orthopaedic Surgeons [AAOS], and Endo-Klinik) and 2 acetabular (Paprosky, AAOS) bone stock loss classification systems were evaluated for reliability. Four observers (2 consultants, 2 registrars) graded the bone loss in 25 patients using preoperative radiographs. Grading was repeated after a minimum of 2 weeks. Interobserver and intraobserver reliability was investigated. The kappa statistic was used to assess levels of agreement. Intraobserver agreement ranged from poor to good. Interobserver agreement ranged from fair to moderate. The validity of the Paprosky classification system was evaluated, comparing preoperative bone stock loss assessment with intraoperative findings. Agreement levels of moderate (femoral classification system) to good (acetabular classification system) were achieved. Bone stock loss classification systems are shown to be inconsistent and unreliable.

  1. Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study

    NARCIS (Netherlands)

    A.E. Hak (Liesbeth); H.A.P. Pols (Huib); A.M. van Hemert (Bert); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2000-01-01

    textabstractofferosclerosis and osteoporosis are major causes of morbidity and mortality in postmenopausal women and have been suggested to be associated. No study has examined whether progression of atherosclerotic calcification is associated with bone loss. In the

  2. Post-traumatic bone mineral loss in tibial shaft fractures treated with a weight-bearing brace.

    Science.gov (United States)

    Andersson, S M; Nilsson, B E

    1979-12-01

    The bone mineral content in the upper ends of the tibia and the fibula was measured in 27 patients with tibial shaft fracture. The loss of bone mineral associated with the fracture did not differ between patients who were allowed weight-bearing in a functional below-knee brace and patients treated with a long leg plaster cast without weight-bearing.

  3. A Radiographic Comparison of Progressive and Conventional Loading on Crestal Bone Loss and Density in Single Implants

    Directory of Open Access Journals (Sweden)

    Majid Sorouri

    2013-01-01

    Full Text Available Objectives: Crestal bone loss is a biologic complication in implant dentistry. The aim of this study was to compare the effect of progressive and conventional loading on crestal bone height and bone density around single osseointegrated implants in posterior maxilla by a longitudinal radiographic assessment technique.Materials and methods: Twenty micro thread implants were placed in 10 patients (two implants per patient. One of the two implants of each patient was assigned to progressive and the other to conventional loading groups. Eight weeks after surgery, conventional implants were restored with a metal ceramic crown and progressive group underwent a progressive loading protocol. The progressive loading group takes different temporary acrylic crowns at 2, 4 and 6 months. After eight months, acrylic crowns were replaced with metal ceramic crown. Computer radiography of both progressive and conventional implants was taken at 2, 4, 6, and 12 months. Image analysis was performed to measure height of crestal bone loss and bone density.Results: The mean values of crestal bone loss at month 12 were 0.11 (0.19 mm for progressively and 0.36 (0.36 mm for conventionally loaded implants, with a statistically significant difference (P 0.05.Conclusion: Progressive group showed less crestal bone loss in single osseointegrated implant than conventional group. Bone density around progressively loaded implants showed increase in crestal, middle and apica

  4. Loss of functional NADPH oxidase-2 protects against alcohol-induced bone resorption in female p47phox-/- mice

    Science.gov (United States)

    In bone, oxidant signaling through NADPH oxidase (NOX)-derived reactive oxygen species (ROS) is an important stimulus for osteoclast differentiation and activity. We have previously demonstrated that chronic alcohol abuse produces bone loss through NOX-dependent mechanisms. In the current study, s...

  5. Retaining Residual Ovarian Tissue following Ovarian Failure Has Limited Influence on Bone Loss in Aged Mice

    Directory of Open Access Journals (Sweden)

    Zelieann R. Craig

    2010-01-01

    Full Text Available Previous work showed that retaining residual ovarian tissue protects young mice from accelerated bone loss following ovarian failure. The present study was designed to determine whether this protection is also present in aged animals. Aged (9–12 months C57BL/6Hsd female mice were divided into: CON (vehicle, VCD (160 mg/kg; 15d, or OVX (ovariectomized. Lumbar BMD was monitored by DXA and μCT used to assess vertebral microarchitecture. BMD was not different between VCD and CON at any time point but was lower (P<.05 than baseline, starting 1 month after ovarian failure in VCD and OVX mice. Following μCT analysis there were no differences between CON and VCD, but OVX mice had lower bone volume fraction, trabecular thickness, and a trend for decreased connectivity density. These findings provide evidence that retention of residual ovarian tissue may protect aged follicle-depleted mice from accelerated bone loss to a lesser extent than that observed in young mice.

  6. Bone-anchored hearing aids in conductive and mixed hearing losses: why do patients reject them?

    Science.gov (United States)

    Siau, Richard T K; Dhillon, Baljeet; Siau, Derrick; Green, Kevin M J

    2016-10-01

    This study aimed to report the bone-anchored hearing aid uptake rate and the reasons for their rejection by patients with conductive and mixed hearing losses. A retrospective review was performed of 113 consecutive patients with unilateral or bilateral conductive or mixed hearing loss referred to the Greater Manchester bone-anchored hearing aid (BAHA) programme between September 2008 and August 2011. 98 (86.7 %) patients were deemed audiologically suitable for BAHA implantation. Of these, 38 (38.8 %) had BAHA implanted; 60 (61.2 %) patients declined. Of those who declined, 27 (45 %) cited anxiety over surgery, 18 (30 %) cited cosmetic reasons, 16 (26.7 %) perceived limited benefit from the device and six (10 %) preferred conventional hearing aids. Our study highlights a 38.8 % BAHA uptake rate in audiologically suitable patients. The main reasons cited for rejection of BAHA were anxiety over surgery and cosmetic concerns. It is important that clinicians address these early during consultation with prospective BAHA recipients and avoid rushing to implant these patients with a bone-anchored hearing aid.

  7. Fermented soybeans by Rhizopus oligosporus reduce femoral bone loss in ovariectomized rats.

    Science.gov (United States)

    Yoo, Hyun-Wook; Chang, Moon-Jeong; Kim, Sun-Hee

    2014-10-01

    Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ovx) old rats as a model of menopause. In the pilot test, a total of 24 seven-week-old female Sprague-Dawley (SD) rats were fed one of three diets for a period of four weeks: casein, unfermented soybean product, or fermented soybean product by R. oligosporus. In the ovx rat model, 20-week-old SD rats weighing 260-290 g underwent either sham-operation (n = 10) or bilateral ovariectomy (n = 30) and were then fed the AIN-93M diet for one week. Thereafter, rats were fed sham-casein, ovx-casein, ovx-soybean, or ovx-fermented soybean diet for five weeks. After decapitation, femoral bones were isolated and preserved in 9% formalin for assessment of bone mineral density (BMD), bone mineral content (BMC), and bone-breaking strength (BBS). Ovx rats showed significantly increased weight gain and decreased uterine wet weight. Of particular interest, ovx rats fed fermented soybeans showed increased uterine wet weights compared to control rats. Fermented soybean diet caused a significant increase in plasma 17-β estradiol concentrations in young rats, and 17-β estradiol levels were enhanced in ovx rats to match those of sham-operated ones. Significantly lower femoral BMD and BMC were observed in ovx rats compared to sham-operated controls, whereas bone areas did not differ statistically among the groups. In addition, BBS tended to be increased in ovx rats fed soybeans and fermented soybeans. Supplementation of fermented soybeans could have preventive and therapeutic effects against osteoporosis in postmenopausal

  8. Relationship Between Osteoporosis and Marginal Bone Loss in Osseointegrated Implants: A 2-Year Retrospective Study.

    Science.gov (United States)

    Corcuera-Flores, José R; Alonso-Domínguez, Ana M; Serrera-Figallo, M Ángeles; Torres-Lagares, Daniel; Castellanos-Cosano, Lizett; Machuca-Portillo, Guillermo

    2016-01-01

    Fitting implants in osteoporotic patients has traditionally been controversial, and there is little scientific evidence relating osteoporosis to marginal bone loss (MBL). The aims of this study are as follows: 1) to evaluate the possibility of a correlation between osteoporosis, as measured by the mandibular cortical index (MCI), and MBL and 2) to assess how various systemic diseases, periodontitis, and placement of implants in regenerated bone are correlated with MBL and MCI. This retrospective study examines 212 implants inserted in 67 patients. To take a possible cluster failure into account, an implant for each patient was selected (n = 67 implants). MBL was assessed. Osteoporosis was evaluated using the MCI. Both MBL and MCI were assessed from panoramic radiographs. χ(2) test was performed (Haberman post hoc test). Significance was P implant (N = 212) was evaluated, a significant association was found between the presence of osteoporosis and MCI (P implants in regenerated sites (P periodontitis (P implants (one per patient, n = 67), significant differences appear to relate only to the MBL with the placement of implants in regenerated bone sites (P periodontitis and especially the placement of implants at sites of bone regeneration.

  9. Bone-anchored hearing aids and unilateral sensorineural hearing loss: why do patients reject them?

    Science.gov (United States)

    Siau, D; Dhillon, B; Andrews, R; Green, K M J

    2015-04-01

    This study aimed to report the bone-anchored hearing aid uptake and the reasons for their rejection by unilateral sensorineural deafness patients. A retrospective review of 90 consecutive unilateral sensorineural deafness patients referred to the Greater Manchester Bone-Anchored Hearing Aid Programme between September 2008 and August 2011 was performed. In all, 79 (87.8 per cent) were deemed audiologically suitable: 24 (30.3 per cent) eventually had a bone-anchored hearing aid implanted and 55 (69.6 per cent) patients declined. Of those who declined, 26 (47.3 per cent) cited perceived limited benefits, 18 (32.7 per cent) cited reservations regarding surgery, 13 (23.6 per cent) preferred a wireless contralateral routing of sound device and 12 (21.8 per cent) cited cosmetic reasons. In all, 32 (40.5 per cent) suitable patients eventually chose the wireless contralateral routing of sound device. The uptake rate was 30 per cent for audiologically suitable patients. Almost half of suitable patients did not perceive a sufficient benefit to proceed to device implantation and a significant proportion rejected it. It is therefore important that clinicians do not to rush to implant all unilateral sensorineural hearing loss patients with a bone-anchored hearing aid.

  10. Project Healthy Bones: An Osteoporosis Prevention Program for Older Adults.

    Science.gov (United States)

    Klotzbach-Shimomura, Kathleen

    2001-01-01

    Project Healthy Bones is a 24-week exercise and education program for older women and men at risk for or who have osteoporosis. The exercise component is designed to improve strength, balance, and flexibility. The education curriculum stresses the importance of exercise, nutrition, safety, drug therapy, and lifestyle factors. (SK)

  11. Weight-loss-associated changes in bone mineral density and bone turnover after partial weight regain with or without aerobic exercise in obese women.

    Science.gov (United States)

    Hinton, P S; Rector, R S; Linden, M A; Warner, S O; Dellsperger, K C; Chockalingam, A; Whaley-Connell, A T; Liu, Y; Thomas, T R

    2012-05-01

    Moderate, long-term weight loss results in the loss of bone mass in overweight or obese premenopausal women. However, whether these changes persist during weight maintenance or regain remains to be determined. Overweight or obese (body mass index: 25.8-42.5 kg/m(2)) women (n=40) with at least two risk factors for the metabolic syndrome participated in this 12-month study that examined the effects of prescribed weight loss and regain, with or without exercise, on bone turnover and on bone mineral density (BMD) in a subset of participants (n=24). During the first 6 month, participants lost ≈ 10% of their initial body weight via energy restriction and supervised aerobic exercise. Following weight loss, participants were randomly assigned to either an exercise or a no exercise treatment for the regain (+50% of weight lost) phase. A one-way (time) repeated measures one-factor analysis of variance (RMANOVA) tested the effects of weight loss on BMD and bone turnover, and a two-way RMANOVA (time, exercise) was used to examine the effects of exercise during weight regain. Hip (P=0.007) and lumbar spine (P=0.05) BMD decreased with weight loss, and remained reduced after weight regain with or without exercise. Likewise, the weight-loss-associated increases in osteocalcin (Pexercise. The