Skeletal Geometry and Indices of Bone Strength in Artistic Gymnasts

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Dowthwaite, Jodi N.; Scerpella, Tamara A.

2010-01-01

This review addresses bone geometry and indices of skeletal strength associated with exposure to gymnastic loading during growth. A brief background characterizes artistic gymnastics as a mechanical loading model and outlines densitometric techniques, skeletal outcomes and challenges in assessment of skeletal adaptation. The literature on bone geometric adaptation to gymnastic loading is sparse and consists of results for disparate skeletal sites, maturity phases, gender compositions and assessment methods, complicating synthesis of an overriding view. Furthermore, most studies assess only females, with little information on males and adults. Nonetheless, gymnastic loading during growth appears to yield significant enlargement of total and cortical bone geometry (+10 to 30%) and elevation of trabecular density (+20%) in the forearm, yielding elevated indices of skeletal strength (+20 to +50%). Other sites exhibit more moderate geometric and densitometric adaptations (5 to 15%). Mode of adaptation appears to be site-specific; some sites demonstrate marked periosteal and endosteal expansion, whereas other sites exhibit negligible or moderate periosteal expansion coupled with endocortical contraction. Further research is necessary to address sex-, maturity- and bone tissue-specific adaptation, as well as maintenance of benefits beyond loading cessation. PMID:19949278

The skeletal vascular system - Breathing life into bone tissue.

Science.gov (United States)

Stegen, Steve; Carmeliet, Geert

2017-08-26

During bone development, homeostasis and repair, a dense vascular system provides oxygen and nutrients to highly anabolic skeletal cells. Characteristic for the vascular system in bone is the serial organization of two capillary systems, each typified by specific morphological and physiological features. Especially the arterial capillaries mediate the growth of the bone vascular system, serve as a niche for skeletal and hematopoietic progenitors and couple angiogenesis to osteogenesis. Endothelial cells and osteoprogenitor cells interact not only physically, but also communicate to each other by secretion of growth factors. A vital angiogenic growth factor is vascular endothelial growth factor and its expression in skeletal cells is controlled by osteogenic transcription factors and hypoxia signaling, whereas the secretion of angiocrine factors by endothelial cells is regulated by Notch signaling, blood flow and possibly hypoxia. Bone loss and impaired fracture repair are often associated with reduced and disorganized blood vessel network and therapeutic targeting of the angiogenic response may contribute to enhanced bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents.

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McCormack, Shana E; Chesi, Alessandra; Mitchell, Jonathan A; Roy, Sani M; Cousminer, Diana L; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Mahboubi, Soroosh; Winer, Karen K; Kelly, Andrea; Grant, Struan Fa; Zemel, Babette S

2017-01-01

More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (∼0.33 years, p ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self-report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

Science.gov (United States)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

1995-01-01

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

Science.gov (United States)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

1995-01-01

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

Importance of antiresorptive therapies for patients with bone metastases from solid tumors

International Nuclear Information System (INIS)

Talreja, Draupadi B

2012-01-01

Patients with bone metastases are at risk of skeletal-related events such as pathologic fractures, spinal cord compression, the need for orthopedic surgery to bone, and palliative radiotherapy for severe bone pain. Antiresorptive therapies have demonstrated efficacy for reducing the risk of skeletal-related events and ameliorating bone pain. Despite the well documented clinical benefits of antiresorptive therapies, patient benefits can be limited or compromised by nonadherence with scheduled therapy. Potential reasons for poor compliance include lack of understanding of how antiresorptive therapies work, neglecting the importance of bone health in maintaining quality of life, and being unaware of the potentially debilitating effects of skeletal-related events caused by bone metastases. Indeed, patients may stop therapy after bone pain subsides or discontinue due to generally mild and usually manageable adverse events, leaving them at an increased risk of developing skeletal-related events. In addition, the cost of antiresorptive therapy can be a concern for many patients with cancer. Medical care for patients with cancer requires a coordinated effort between primary care physicians and oncologists. Patients’ medical care teams can be leveraged to help educate them about the importance of adherence to antiresorptive therapy when cancer has metastasized to bone. Because primary care physicians generally have more contact with their patients than oncologists, they are in a unique position to understand patient perceptions and habits that may lead to noncompliance and to help educate patients about the benefits and risks of various antiresorptive therapies in the advanced cancer setting. Therefore, primary care physicians need to be aware of various mechanistic and clinical considerations regarding antiresorptive treatment options

Bone turnover markers and bone scintigraphy in the evaluation of skeletal metastases

International Nuclear Information System (INIS)

Chrapko, B.; Nocun, A.; Golebiewska, R.; Jankowska, H.; Zaorska-Rajca, J.

2005-01-01

The aim of this study was evaluation of the clinical usefulness of bone scintigraphy and of serum bone turnover marker levels in the assessment of skeletal metastases. We investigated 60 patients with suspected skeletal metastases. Serum level of bone-formation marker: amino- terminal propeptide of type I procollagen (PINP) and a bone-degradation marker: carboxy-terminal telopeptide of type I collagen (ICTP) were assessed with radioimmunoassays. Bone MDP- 99m- Tc scans were performed as well. Hot spots were showed in 72% of patients. According to bone scintigraphy the patients were divided in to 3 groups: Group I - without hot spots (n = 16; 26%), Group II up to 10 hot spots (n = 25; 42%) and Group III more that 10 hot spots (n = 19; 32%). Mean serum level of ICTP was significantly higher in Group II than in Group I (p < 0.05), as well as in Group III compared to Group II (p < 0.001) and in Group III compared to Group I (p < 0.001). There is only one significant relationship in PINP levels - between Groups II and III. The levels of bone pathological degradation (ICTP) and bone formation reflect the metastatic disease extent in bone. Serum ICTP level is more useful in staging metastasis. Significantly higher PINP reflects only a much disseminated process. (author)

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

Science.gov (United States)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

1995-01-01

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p anabolic actions of GH.

Bone and bone marrow scintigraphy in the diagnosis of neoplastic involvement of the skeletal system

International Nuclear Information System (INIS)

Sacchi, S.; Marietta, M.; Rinaldi, G.; Torelli, U.; Pantusa, M.; Romani, F.; Zaniol, P.

1987-01-01

Bone and bone marrow scintigraphy has been performed in 16 patients with epithelial tumor or lymphoproliferative diseases and in 22 patients affected by multiple myeloma. The first technique revealed skeletal alterations in 60.5% of all the patients; the second in 42.1%. In 21 cases, however, there was agreement between bone and bone marrow radionuclide imaging, making possible a more accurate etiological diagnosis of the hot areas found in skeletal scintigraphy. In patients with multiple myeloma we found a high correlation between the marrow distribution pattern and the plasmocytoma staging accoding to Durie and Salmon. It is thoght therefore that bone marrow scintigraphy may be useful sice it provides a further diagnostic tool for a better clinical staging of patients with multiple myeloma

Importance of antiresorptive therapies for patients with bone metastases from solid tumors

Directory of Open Access Journals (Sweden)

Talreja DB

2012-09-01

Full Text Available Draupadi B TalrejaDepartment of Medicine, David Geffen School of Medicine at UCLA and Northridge Hospital Medical Center, Northridge, CA, USAAbstract: Patients with bone metastases are at risk of skeletal-related events such as pathologic fractures, spinal cord compression, the need for orthopedic surgery to bone, and palliative radiotherapy for severe bone pain. Antiresorptive therapies have demonstrated efficacy for reducing the risk of skeletal-related events and ameliorating bone pain. Despite the well documented clinical benefits of antiresorptive therapies, patient benefits can be limited or compromised by nonadherence with scheduled therapy. Potential reasons for poor compliance include lack of understanding of how antiresorptive therapies work, neglecting the importance of bone health in maintaining quality of life, and being unaware of the potentially debilitating effects of skeletal-related events caused by bone metastases. Indeed, patients may stop therapy after bone pain subsides or discontinue due to generally mild and usually manageable adverse events, leaving them at an increased risk of developing skeletal-related events. In addition, the cost of antiresorptive therapy can be a concern for many patients with cancer. Medical care for patients with cancer requires a coordinated effort between primary care physicians and oncologists. Patients' medical care teams can be leveraged to help educate them about the importance of adherence to antiresorptive therapy when cancer has metastasized to bone. Because primary care physicians generally have more contact with their patients than oncologists, they are in a unique position to understand patient perceptions and habits that may lead to noncompliance and to help educate patients about the benefits and risks of various antiresorptive therapies in the advanced cancer setting. Therefore, primary care physicians need to be aware of various mechanistic and clinical considerations regarding

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population.

Science.gov (United States)

Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

2015-01-01

Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean Population.

Directory of Open Access Journals (Sweden)

Eun Jin Woo

Full Text Available Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.

Bone scintigraphy in children with obscure skeletal pain

International Nuclear Information System (INIS)

Majd, Massoud

1979-01-01

In a group of 82 children with focal or generalized skeletal pain of obscure etiology, the radionuclide skeletal scintigraphy was the only, or the most informative, clue to the diagnosis of a variety of benign and malignant conditions. It is strongly recommended that any unexplained bone or joint pain in children be evaluated by this non-invasive technique [fr

The chondrocytic journey in endochondral bone growth and skeletal dysplasia.

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Yeung Tsang, Kwok; Wa Tsang, Shun; Chan, Danny; Cheah, Kathryn S E

2014-03-01

The endochondral bones of the skeleton develop from a cartilage template and grow via a process involving a cascade of chondrocyte differentiation steps culminating in formation of a growth plate and the replacement of cartilage by bone. This process of endochondral ossification, driven by the generation of chondrocytes and their subsequent proliferation, differentiation, and production of extracellular matrix constitute a journey, deviation from which inevitably disrupts bone growth and development, and is the basis of human skeletal dysplasias with a wide range of phenotypic severity, from perinatal lethality to progressively deforming. This highly coordinated journey of chondrocyte specification and fate determination is controlled by a myriad of intrinsic and extrinsic factors. SOX9 is the master transcription factor that, in concert with varying partners along the way, directs the different phases of the journey from mesenchymal condensation, chondrogenesis, differentiation, proliferation, and maturation. Extracellular signals, including bone morphogenetic proteins, wingless-related MMTV integration site (WNT), fibroblast growth factor, Indian hedgehog, and parathyroid hormone-related peptide, are all indispensable for growth plate chondrocytes to align and organize into the appropriate columnar architecture and controls their maturation and transition to hypertrophy. Chondrocyte hypertrophy, marked by dramatic volume increase in phases, is controlled by transcription factors SOX9, Runt-related transcription factor, and FOXA2. Hypertrophic chondrocytes mediate the cartilage to bone transition and concomitantly face a live-or-die situation, a subject of much debate. We review recent insights into the coordination of the phases of the chondrocyte journey, and highlight the need for a systems level understanding of the regulatory networks that will facilitate the development of therapeutic approaches for skeletal dysplasia. Copyright © 2014 Wiley Periodicals

Skeletal metastases in pancreatic carcinoma: study by isotopic bone scanning

Energy Technology Data Exchange (ETDEWEB)

Hatfield, D R; Deland, F H; Maruyama, Y

1976-01-01

A review of the literature of 2,155 reported patients with primary carcinoma of the pancreas, revealed 110 cases or 5 percent to have skeletal metastasis by radiographic or autopsy study. A study conducted over a 2 year period disclosed that 1 case of skeletal metastasis was detected by bone scanning in 16 patients with pancreatic carcinoma. This indicates a minimum skeletal metastasis rate of 6 percent. We feel these percentages are low and can be further defined by the more routine employment of the bone scan to evaluate patients with carcinoma of the pancreas. The true figure may be much higher, perhaps as high as 20 percent.

Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

DEFF Research Database (Denmark)

Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.

2003-01-01

OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystopl......OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment......, colocystoplasty, and controls. All animals received antibiotics for 1 week after surgery; half of each group remained on oral antibiotics. Bone-related biochemistry was measured in serum and urine. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT) were used to determine bone...... no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P

Cartilage and bone cells do not participate in skeletal regeneration in Ambystoma mexicanum limbs.

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McCusker, Catherine D; Diaz-Castillo, Carlos; Sosnik, Julian; Q Phan, Anne; Gardiner, David M

2016-08-01

The Mexican Axolotl is one of the few tetrapod species that is capable of regenerating complete skeletal elements in injured adult limbs. Whether the skeleton (bone and cartilage) plays a role in the patterning and contribution to the skeletal regenerate is currently unresolved. We tested the induction of pattern formation, the effect on cell proliferation, and contributions of skeletal tissues (cartilage, bone, and periosteum) to the regenerating axolotl limb. We found that bone tissue grafts from transgenic donors expressing GFP fail to induce pattern formation and do not contribute to the newly regenerated skeleton. Periosteum tissue grafts, on the other hand, have both of these activities. These observations reveal that skeletal tissue does not contribute to the regeneration of skeletal elements; rather, these structures are patterned by and derived from cells of non-skeletal connective tissue origin. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone-seeking radiopharmaceuticals in skeletal malignancy: evolution, not revolution

International Nuclear Information System (INIS)

MacFarlane, D.

2003-01-01

Many advanced malignancies are complicated by skeletal metastases, with attendant pain and disability. External beam radiotherapy is still the most effective treatment for isolated lesions. Bone-seeking radiopharmaceuticals were perceived as a means of delivering radiation to multiple lesions simultaneously. A wide variety of radioisotopes have been used in this endeavor, with myelosuppression being the most significant potential adverse effect. Benefits of treatment are modest, including a transient improvement in pain control and perhaps prolongation of the treatment-free period. This is best demonstrated in prostate cancer with lower responses by skeletal metastases from breast and lung cancers. However, the treatment is yet to produce any improvement in patient survival. Experimental approaches to improve treatment efficacy include combination with cytotoxic therapy, and administration earlier in the course of the disease. Bone seeking radiopharmaceuticals have been used in treatment of advanced osteosarcoma in humans and canines and achieved effective palliation. The myelosuppressive effects of these agents have been exploited in patients with multiple myeloma to assist in attaining myeloablation prior to stem cell transplantation. Development of more potent non-radiolabelled bisphosphonates and recognition of their antitumour effect against several tumours has sparked a recrudescence of interest in their use for bone metastases. Set against these developments, the role of bone-seeking radiopharmaceuticals in skeletal metastases may need to be redefined

The Bone Dysplasia Ontology: integrating genotype and phenotype information in the skeletal dysplasia domain

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Groza Tudor

2012-03-01

Full Text Available Abstract Background Skeletal dysplasias are a rare and heterogeneous group of genetic disorders affecting skeletal development. Patients with skeletal dysplasias suffer from many complex medical issues including degenerative joint disease and neurological complications. Because the data and expertise associated with this field is both sparse and disparate, significant benefits will potentially accrue from the availability of an ontology that provides a shared conceptualisation of the domain knowledge and enables data integration, cross-referencing and advanced reasoning across the relevant but distributed data sources. Results We introduce the design considerations and implementation details of the Bone Dysplasia Ontology. We also describe the different components of the ontology, including a comprehensive and formal representation of the skeletal dysplasia domain as well as the related genotypes and phenotypes. We then briefly describe SKELETOME, a community-driven knowledge curation platform that is underpinned by the Bone Dysplasia Ontology. SKELETOME enables domain experts to use, refine and extend and apply the ontology without any prior ontology engineering experience--to advance the body of knowledge in the skeletal dysplasia field. Conclusions The Bone Dysplasia Ontology represents the most comprehensive structured knowledge source for the skeletal dysplasias domain. It provides the means for integrating and annotating clinical and research data, not only at the generic domain knowledge level, but also at the level of individual patient case studies. It enables links between individual cases and publicly available genotype and phenotype resources based on a community-driven curation process that ensures a shared conceptualisation of the domain knowledge and its continuous incremental evolution.

The mechanism of uptake of bone-seeking isotopes by skeletal metastases

International Nuclear Information System (INIS)

Galasko, C.S.B.

1977-01-01

Although skeletal scintigraphy has become accepted as an extremely useful method of examining the skeleton, particularly for the early detection of skeletal metastases and the assessment of their response to therapy, the underlying pathological changes which allow this use of isotopes are not well understood. This study was undertaken in man and in the experimental animal in an attempt to explain the underlying mechanism for skeletal scintigraphy. Autopsy specimens indicated that tumour invasion of bone, with the possible exception of lymphomata, is associated with a significant increase in new bone production, shown by an increase in the amount of osteoid tissue and particularly immature woven bone. The animal experiments indicated that there are two mechanisms for this new bone formation. These different mechanisms may explain the different radiographic appearances. Irrespective of the mechanism of production, this new bone had a markedly increased avidity for bone-seeking isotopes. When the tumour was successfully irradiated the bone lost its osteoblastic reaction, and the production of immature new bone ceased as did the increased uptake of bone-seeking isotopes. Investigation of the vascularity of the lesion showed that there was an increase in small vessels in the neighbourhood of the tumour. The results of the study suggest that the uptake of isotope occurs in two phases. During the first phase, which occurs very rapidly, large amounts of isotope accumulate in the extracellular fluid following the increased vascularity. In the second slower phase, the isotope is gradually concentrated by the reactive immature new woven bone. (author)

A Modified method for reducing renal injury in zoledronic acid treatment of hypercalcemia and adverse skeletal events

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Jiang Liu

2013-01-01

Full Text Available Aims: In this paper, we have reported a previously undescribed risk factor of deterioration of renal function in zoledronic acid treatment of skeletal metastasis - high serum calcium level. Based on this consideration, a modified method of treatment of hypercalcemia (HCM with zoledronic acid is suggested in this paper. Material and Methods: Bone scan findings of 1090 cancer patients were analyzed, of which 26 had intense renal parenchymal uptake as a result of HCM or bone metastases. Subsequently, a total of 56 bone metastases patients with zoledronic acid treatment were divided into three groups: HCM group who were pre-treated to normal serum calcium level (13 patients, HCM group (19 patients, and normal serum calcium group (24 patients. Results: More patients with intense renal parenchymal uptake were hyperglycemic, statistically significantly (18/26 versus 19/1064, P = 2.1, E-78. No more patients with intense renal parenchymal uptake were associated with bone metastases (14/26 versus 438/1064, P = 0.20. Subsequently, more HCM patients receiving zoledronic acid treatment showed renal injury compared to patients with normal serum calcium level (5/15 versus 2/24, P < 0.05 and HCM patients with pre-treatment to normal serum calcium level (5/15 versus 1/17, P < 0.05. Conclusions: Intense renal parenchymal uptake of bisphosphonates is closely related to HCM rather than to bone metastases in cancer patients. The serum calcium should be measured and reduced to normal level before zoledronic acid is used in managements of adverse skeletal events in order to decrease the risk of renal injury.

Lasting consequences of traumatic events on behavioral and skeletal parameters in a mouse model for post-traumatic stress disorder (PTSD).

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Yu, Hongrun; Watt, Heather; Kesavan, Chandrasekhar; Johnson, Patrick J; Wergedal, Jon E; Mohan, Subburaman

2012-01-01

Post-traumatic stress disorder (PTSD) is an anxiety disorder that not only affects mental health, but may also affect bone health. However, there have been no studies to examine the direct relationship between PTSD and bone. We employed electric shocks in mice to simulate traumatic events that cause PTSD. We also injected the anxiogenic drug FG-7142 prior to electric shocks. Electric shocks created lasting conditioned fear memory in all mice. In young mice, electric shocks elicited not only behavioral response but also skeletal response, and injection of FG-7142 appeared to increase both types of response. For example in behavioral response within the first week, mice shocked alone froze an average of 6.2 sec in 10 sec tests, and mice injected with FG-7142 froze 7.6 sec, both significantly different (PPTSD-like behavior was associated with reduced bone mass acquisition. This is the first study to document evidence that traumatic events induce lasting consequences on both behavior and skeletal growth, and electric shocks coupled with injection of anxiogenic FG-7142 in young mice can be used as a model to study the effect of PTSD-like symptoms on bone development.

The BoneXpert method for automated determination of skeletal maturity

DEFF Research Database (Denmark)

Thodberg, Hans Henrik; Kreiborg, Sven; Juul, Anders

2009-01-01

Bone age rating is associated with a considerable variability from the human interpretation, and this is the motivation for presenting a new method for automated determination of bone age (skeletal maturity). The method, called BoneXpert, reconstructs, from radiographs of the hand, the borders...... component analysis; 3) the consensus bone age concept that defines bone age of each bone as the best estimate of the bone age of the other bones in the hand; 4) a common bone age model for males and females; and 5) the unified modelling of TW and GP bone age. BoneXpert is developed on 1559 images...

Health Resource Utilization Associated with Skeletal-Related Events in Patients with Advanced Prostate Cancer: A European Subgroup Analysis from an Observational, Multinational Study

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Amit Bahl

2014-07-01

Full Text Available This study aimed to increase the understanding of health resource utilization (HRU associated with skeletal-related events (SREs occurring in patients with bone metastases secondary to advanced prostate cancer. A total of 120 patients from Germany, Italy, Spain and the United Kingdom were enrolled in this observational study. They had bone metastases secondary to prostate cancer and had experienced at least one SRE in the 97 days before giving informed consent. HRU data were collected retrospectively for 97 days before enrolment and prospectively for up to 18–21 months. HRU, including the number and duration of inpatient hospitalizations, number of outpatient and emergency department visits and procedures, was independently attributed by investigators to an SRE. Of the 222 SREs included in this analysis, 26% were associated with inpatient stays and the mean duration per SRE was 21.4 days (standard deviation (SD 17.8 days. Overall, 174 SREs (78% required an outpatient visit and the mean number of visits per SRE was 4.6 (SD 4.6. All SREs are associated with substantial HRU. Preventing SREs in patients with advanced prostate cancer and bone metastases may help to reduce the burden to both patients and European healthcare systems.

FDG-PET response of skeletal (bone marrow and bone) involvement after induction chemotherapy in pediatric Hodgkin lymphoma - Are specific response criteria required?

Science.gov (United States)

Georgi, Thomas Walter; Kluge, Regine; Kurch, Lars; Chavdarova, Lidia; Hasenclever, Dirk; Stoevesandt, Dietrich; Pelz, Tanja; Landman-Parker, Judith; Wallace, Hamish; Karlen, Jonas; Fernandez-Teijeiro, Ana; Cepelova, Michaela; Fossa, Alexander; Balwierz, Walentyna; Attarbaschi, Andishe; Ammann, Roland A; Pears, Jane; Hraskova, Andrea; Uyttebroeck, Anne; Beishuizen, Auke; Dieckmann, Karin; Leblanc, Thierry; Daw, Stephen; Baumann, Julia; Körholz, Dieter; Sabri, Osama; Mauz-Körholz, Christine

2018-04-13

Purpose: This study focused on skeletal involvement in FDG-PET (PET) in Hodgkin lymphoma (HL). We aimed at a systematic evaluation of the different types of skeletal involvement and their PET response after two cycles of chemotherapy (PET-2), to answer the question whether the current PET response criterion for skeletal involvement is suitable. A secondary objective was to observe the influence of initial uptake intensity and metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: Initial PET scans (PET-0) of 1068 pediatric HL patients from the EuroNet-PHL-C1 (C1) trial were evaluated by central review for skeletal involvement. Three types of skeletal lesions were distinguished: skeletal lesions detected only in PET (PETonly), bone marrow (BM) lesions confirmed by MRI or BM biopsy and bone lesions. Uptake intensity (measured as qPET value) and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response in PET-2 of skeletal and nodal involvement were compared. Results: 139/1068 (13%) C1 patients showed skeletal involvement (44/139 PETonly patients, 32/139 BM patients and 63/139 bone patients). 101/139 (73%) patients became PET-2 negative in the skeleton while lymph node involvement was PET-2 negative in 94/139 (68%) patients. Highest skeletal PET-2 negative rate was seen in 42/44 (95%) PETonly patients, followed by 22/32 (69%) BM patients and 37/63 (59%) bone patients. Skeletal lesions who became PET-2 negative showed lower median values for initial qPET (2.74) and MTV (2ml) than lesions who remained PET-2 positive (3.84; 7ml). Conclusion: In this study with pediatric HL patients, the complete response rate in PET-2 of skeletal and nodal involvement was similar. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion - comparison with the local skeletal background - is well suited. Initial uptake intensity and MTV of

Total skeletal uptake of diphosphonate in Paget's bone disease and rheumatoid arthritis

International Nuclear Information System (INIS)

Cabrejas, M.J.; Mautclen, C.A.; Fromm, G.

1982-01-01

Sup(99m) Technetium-diphosphonates (99m-Tc-DP) are very satifactory agents to quantify total skeletal uptake (TSU) in normal and pathological conditions. Although the intimate mechanism of skeletal localization of 99m-Tc-DP is not completely understood the test appears to be a very sensitive index of increased bone turnover. TSU can be determined by several methods: urine collection, whole body counter retention and gamma camara body retention studies. The urine collection method seems to be an easy and reliable method, having the advantage that no expensive device is needed. Further studies on the skeletal uptake of 99m-Tc-DP, in normal subjects and pathological conditions, with special emphasis on patients with rheumatoid arthritis, are reported. Correlation of these data with other tests indicating bone turnover, such as cortical bone loss determined by densitometry or urinary hydroxyproline excretion, supports previous reports that the TSU is a useful parameter to evaluate bone metabolism

Natural history of malignant bone disease in hepatocellular carcinoma: final results of a multicenter bone metastasis survey.

Directory of Open Access Journals (Sweden)

Daniele Santini

Full Text Available BACKGROUND: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC. Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs, and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. RESULTS: The median age was 70 years; 172 patients were male (81.5%. The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis; 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%. Most of these lesions were osteolytic (82.4%; 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819. The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005, ECOG performance status (p = 0.002 and treatment with bisphosphonate (p = 0.024 were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE (p = 0.021 and OS (p = 0.001. CONCLUSIONS: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.

Does bone measurement on the radius indicate skeletal status. Concise communication

International Nuclear Information System (INIS)

Mazess, R.B.; Peppler, W.W.; Chesney, R.W.; Lange, T.A.; Lindgren, U.; Smith, E. Jr.

1984-01-01

Single-photon (I-125) absorptiometry was used to measure bone mineral content (BMC) of the distal third of the radius, and dual-photon absorptiometry (Gd-153) was used to measure total-body bone mineral (TBBM), as well as the BMC of major skeletal regions. Measurements were done in normal females, normal males, osteoporotic females, osteoporotic males, and renal patients. The BMC of the radius predicted TBBM well in normal subjects, but was less satisfactory in the patient groups. The spinal BMC was predicted with even lower accuracy from radius measurement. The error in predicting areal density (bone mass per unit projected skeletal area) of the lumbar and thoracic spine from the radius BMC divided by its width was smaller, but the regressions differed significantly among normals, osteoporotics, and renal patients. There was a preferential spinal osteopenia in the osteoporotic group and in about half of the renal patients. Bone measurements on the radius can indicate overall skeletal status in normal subjects and to a lesser degree in patients, but these radius measurements are inaccurate, even on the average, as an indicator of spinal state

[Efficacy of zoledronic acid combined with chemotherapy in treatment of skeletal metastases of non-small cell lung cancer and the bone metabolic markers].

Science.gov (United States)

Hu, Xiao-ye; Zou, Qing-feng; Jin, Chuan; Li, Wei-dong; Chen, Wen-sheng; Ma, Lei

2010-06-01

To evaluate the clinical efficacy of zoledronic acid combined with chemotherapy in the management of skeletal metastasis of non-small cell lung cancer (NSCLC) and investigate the value in urine amino-terminal telopeptide of type I collagen (uNTX) and serum bone specific alkaline phosphatase (sBALP) in monitoring skeletal metastasis of NSCLC. From February, 2007 to January, 2009, 32 NSCLC patients with bone metastases received treatment with zoledronic acid at the dose of 4 mg given every 3 weeks and platinum-based chemotherapy (each cycle lasting for 3 weeks). Before and during the treatments, uNTX and sBALP were measured in these patients using ELISA and precipitation with wheat germ lectin, respectively. The patients were followed up for skeletal-related events (SREs) and status of survival. A significant decrease occurred in the pain scores and analgesic use in the patients after the therapy. SREs were not observed during the treatment. Serum creatinine and calcium levels underwent no significant variation during the treatment. Eleven patients reported 14 possible zoledronic acid-related adverse events. The concentration of uNTX and sBALP in patients with bone metastases was above the upper limit of the normal range. A positive correlation was observed between the levels of the markers and the extent of bone metastases. At the third month, uNTX and sBALP were significantly lowered, but radionuclide whole-body bone imaging showed no obvious changes. Of the 32 patients, 24 had elevated uNTX values, which became normal after the treatment in 15 patients and remained elevated in the other 9 patients. SREs occurred in these two subgroups at the rates of 53% and 89% (P=0.039), respectively. Twenty-six patients had elevated sBALP level, and 16 of them exhibited normal sBALP level after the treatment. The incidences of SREs in the patients with elevated and normal sBALP level were 50% and 90% (P=0.038), respectively. The levels of uNTX/Cr and sBALP were not correlated

Co-existent Paget’s Disease of the Bone, Prostate Carcinoma Skeletal Metastases and Fracture on Skeletal Scintigraphy-Lessons to be Learned

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Luke I Sonoda

2013-08-01

Full Text Available Bone scintigraphy, despite being non-specific, is a very sensitive and simple investigation for patients with active Paget’s disease of the bone. Skeletal metastases and Paget’s disease may co-exist in the elderly patients as both conditions are commonly seen in this age group. Clinical and radiological correlation may help to improve the diagnostic specificity of a bone scintigram. We report a patient in whom concurrent Paget’s disease and a rib fracture became evident only on repeat scintigraphy following successful treatment of prostate carcinoma skeletal metastases.

Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain.

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Gualano, Bruno; Rawson, Eric S; Candow, Darren G; Chilibeck, Philip D

2016-08-01

This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline.

Paraphyseal changes on bone-age studies predict risk of delayed radiation-associated skeletal complications following total body irradiation

International Nuclear Information System (INIS)

Kitazono Hammell, Mary T.; Edgar, J.C.; Jaramillo, Diego; Bunin, Nancy

2013-01-01

Children undergoing total body irradiation (TBI) often develop delayed skeletal complications. Bone-age studies in these children often reveal subtle paraphyseal changes including physeal widening, metaphyseal irregularity and paraphyseal exostoses. To investigate whether paraphyseal changes on a bone-age study following TBI indicate a predisposition toward developing other radiation-associated skeletal complications. We retrospectively reviewed medical records and bone-age studies of 77 children receiving TBI at our institution between 1995 and 2008 who had at least 2 years of clinical follow-up and one bone-age study after TBI. We graded bone-age studies according to the severity of paraphyseal changes. All documented skeletal complications following TBI were tabulated. Kendall's tau-b was used to examine associations between degree of paraphyseal change and development of a skeletal complication. Kendall's tau analyses showed that physeal widening and metaphyseal irregularity/sclerosis (tau = 0.87, P < 0.001) and paraphyseal exostoses (tau = 0.68, P < 0.001) seen on bone-age studies were significantly positively associated with the development of delayed skeletal complications following TBI. Thirty percent of children with no or mild paraphyseal changes developed a delayed skeletal complication, compared with 58% of children with moderate paraphyseal changes and 90% of children with severe paraphyseal changes. Paraphyseal changes identified on a bone-age study correlate positively with the development of delayed skeletal complications elsewhere in the skeleton following TBI. (orig.)

Skeletal stem cells and their contribution to skeletal fragility

DEFF Research Database (Denmark)

Aldahmash, A.

2016-01-01

Age-related osteoporotic fractures are major health care problem worldwide and are the result of impaired bone formation, decreased bone mass and bone fragility. Bone formation is accomplished by skeletal stem cells (SSC) that are recruited to bone surfaces from bone marrow microenvironment....... This review discusses targeting SSC to enhance bone formation and to abolish age-related bone fragility in the context of using stem cells for treatment of age-related disorders. Recent studies are presented that have demonstrated that SSC exhibit impaired functions during aging due to intrinsic senescence...

Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials.

Science.gov (United States)

Saad, F; Ivanescu, C; Phung, D; Loriot, Y; Abhyankar, S; Beer, T M; Tombal, B; Holmstrom, S

2017-03-01

We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo. Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments. First SREs caused HRQoL deterioration in both trials. Spinal cord compression had the largest impact, with clinically meaningful reductions in seven of nine FACT-P domains in PREVAIL and all three in AFFIRM (mean (95% confidence interval (CI)) change in FACT-P total score -16.95 (-26.47, -7.44) and -9.69 (-16.10, -3.27), respectively). In PREVAIL, first SREs caused clinically meaningful declines in EQ-5D utility index, irrespective of category; spinal cord compression had the largest impact (mean (95% CI) change -0.24 (-0.39, -0.08)). In AFFIRM, FACT-P and FACT-General total scores showed clinically meaningful declines after radiation/surgery to bone. SREs were associated with clinically meaningful functional declines in the daily lives of patients with mCRPC. Spinal cord compression had the largest impact on HRQoL.

The molecular response of bone to growth hormone during skeletal unloading: regional differences

Science.gov (United States)

Bikle, D. D.; Harris, J.; Halloran, B. P.; Currier, P. A.; Tanner, S.; Morey-Holton, E.

1995-01-01

Hind limb elevation of the growing rat provides a good model for the skeletal changes that occur during space flight. In this model the bones of the forelimbs (normally loaded) are used as an internal control for the changes that occur in the unloaded bones of the hind limbs. Previous studies have shown that skeletal unloading of the hind limbs results in a transient reduction of bone formation in the tibia and femur, with no change in the humerus. This fall in bone formation is accompanied by a fall in serum osteocalcin (bone Gla protein, BGP) and bone BGP messenger RNA (mRNA) levels, but a rise in bone insulin-like growth factor-I (IGF-I) protein and mRNA levels and resistance to the skeletal growth-promoting actions of IGF-I. To determine whether skeletal unloading also induced resistance to GH, we evaluated the response of the femur and humerus of sham and hypophysectomized rats, control and hind limb elevated, to GH (two doses), measuring mRNA levels of IGF-I, BGP, rat bone alkaline phosphatase (RAP), and alpha 1(1)-procollagen (coll). Hypophysectomy (HPX) decreased the mRNA levels of IGF-I, BGP, and coll in the femur, but was either less effective or had the opposite effect in the humerus. GH at the higher dose (500 micrograms/day) restored these mRNA levels to or above the sham control values in the femur, but generally had little or no effect on the humerus. RAP mRNA levels were increased by HPX, especially in the femur. The lower dose of GH (50 micrograms/day) inhibited this rise in RAP, whereas the higher dose raised the mRNA levels and resulted in the appearance of additional transcripts not seen in controls. As for the other mRNAs, RAP mRNA in the humerus was less affected by HPX or GH than that in the femur. Hind limb elevation led to an increase in IGF-I, coll, and RAP mRNAs and a reduction in BGP mRNA in the femur and either had no effect or potentiated the response of these mRNAs to GH. We conclude that GH stimulates a number of markers of bone

Pathogenesis and pharmacological treatment of bone pain in skeletal metastases

Energy Technology Data Exchange (ETDEWEB)

Ripamonti, C. [National Cancer Institute, Rehabilitation, Pain Therapy and Palliative Care Division, Milan (Italy); Fulfaro, F. [Societa' per l' Assistenza al Malato Oncologico Terminale, Palermo (Italy)

2001-03-01

Sixty-five percent of patients with advanced cancer present bone metastases and most of them present a rather slow clinical course characterized by pain, mobility deficiencies and skeletal complications such as fractures and spinal cord compression. Metastatic involvement of the bone is one of the most frequent causes of pain in cancer patients and represents one of the firs signs of widespread neoplastic disease. The pain may originate directly from the plastic disease. The pain may originate directly from the bone, from nerve root compression or from muscle spasms in the area of the lesions. The mechanism of metastatic bone pain is mainly somatic (nociceptive) even though, in some cases, neuropathic and visceral stimulations may overlap. The conventional symptomatic treatment of metastatic bone pain requires the use of multidisciplinary therapies such as radiotherapy in association with systemic treatment (hormonotherapy, chemotherapy, radioisotopes) with the support of analgesic therapy. Recently, studies have indicated the use of bisphosphonates in the treatment of pain and in the prevention of skeletal complications in patients with metastatic bone disease. In some patients pharmacological treatment, radiotherapy, radioisotopes administered alone or in association are not able to manage pain adequately. The role of neuroinvasive techniques in treating metastatic bone pain is debated. The clinical conditions of the patient, his life expectancy and quality of life must guide the physician in the choice of the best possible therapy.

Pathogenesis and pharmacological treatment of bone pain in skeletal metastases

International Nuclear Information System (INIS)

Ripamonti, C.; Fulfaro, F.

2001-01-01

Sixty-five percent of patients with advanced cancer present bone metastases and most of them present a rather slow clinical course characterized by pain, mobility deficiencies and skeletal complications such as fractures and spinal cord compression. Metastatic involvement of the bone is one of the most frequent causes of pain in cancer patients and represents one of the firs signs of widespread neoplastic disease. The pain may originate directly from the plastic disease. The pain may originate directly from the bone, from nerve root compression or from muscle spasms in the area of the lesions. The mechanism of metastatic bone pain is mainly somatic (nociceptive) even though, in some cases, neuropathic and visceral stimulations may overlap. The conventional symptomatic treatment of metastatic bone pain requires the use of multidisciplinary therapies such as radiotherapy in association with systemic treatment (hormonotherapy, chemotherapy, radioisotopes) with the support of analgesic therapy. Recently, studies have indicated the use of bisphosphonates in the treatment of pain and in the prevention of skeletal complications in patients with metastatic bone disease. In some patients pharmacological treatment, radiotherapy, radioisotopes administered alone or in association are not able to manage pain adequately. The role of neuroinvasive techniques in treating metastatic bone pain is debated. The clinical conditions of the patient, his life expectancy and quality of life must guide the physician in the choice of the best possible therapy

Skeletal Class III malocclusion with thin symphyseal bone: a case report.

Science.gov (United States)

Hikida, Eriko; Tanikawa, Chihiro

2012-11-01

To describe the management of a severe skeletal Class III patient with thin symphyseal bone and alveolar bone covering the mandibular incisors. A 24 year-old female presented with a skeletal Class III malocclusion characterised by thin alveolar bone in a mildly crowded, mandibular incisor region. Computerised tomography (CT) assisted in the determination of possible tooth movement within the anterior mandibular alveolar bone. The finalised treatment plan aimed to align the maxillary and mandibular dental arches following the extraction of the maxillary right first premolar and the mandibular right permanent lateral incisor. The surgical repositioning of the maxilla and mandible with a LeFort I osteotomy and a bilateral sagittal split osteotomy (BSSO) would follow. After treatment, an acceptable facial profile and a solid intercuspation of the teeth were obtained. Significant root resorption was not observed. The occlusion remained stable with normal overjet and overbite after two years of retention. CT examination provided an assessment of the three-dimensional morphological characteristics of anterior alveolar bone which enabled an evaluation of possible tooth movement.

Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone

International Nuclear Information System (INIS)

Nieuwenhuyse, J.P. van; Clapuyt, P.; Malghem, J.; Everarts, P.; Melin, J.; Pauwels, S.; Brichard, B.; Ninane, J.; Vermylen, C.; Cornu, G.

1996-01-01

Background. The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood. Objective. To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period. Materials and methods. Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984-1993). Results. Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n = 18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/RBS+ abnormalities (n = 10) were most frequently insignificant. Conclusion. In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed. (orig.). With 2 figs., 4 tabs

Introduction to skeletal radiology and bone growth

International Nuclear Information System (INIS)

Rogers, L.F.

1987-01-01

Radiographic examination is the key to the diagnosis of many skeletal abnormalities. It is essential that each bone be examined in its entirety, including the cortex, medullary canal (cancellous bone or spongiosa), and articular ends. The position and alignment of joints are determined. In children, the epiphysis and epiphyseal line or physis must be observed. The adjacent soft tissues are examined. Obliteration of normal soft-tissue lines and the presence of a joint effusion are of particular importance. When disease is present, it is important to determine whether the process is limited to a single bone or joint or whether multiple bones or joints are involved. The distribution of disease is also a consideration. The presence and type of bone destruction and bone production, the appearance of the edges or borders of the lesion, and the presence or absence of cortical expansion and periosteal reaction are also noted. The radiographic findings are then correlated with the clinical history and the age and sex of the patient to arrive at a logical diagnosis. The diagnosis may be firm in some instances; in other cases, a differential diagnosis is offered since the exact diagnosis cannot be determined

The estrogen-related receptors (ERRs): potential targets against bone loss.

Science.gov (United States)

Zhang, Ling; Wong, Jiemin; Vanacker, Jean-Marc

2016-10-01

Bone loss and the resulting skeletal fragility is induced by several pathological or natural conditions, the most prominent of which being aging as well as the decreased levels of circulating estrogens in post-menopause females. To date, most treatments against bone loss aim at preventing excess bone resorption. We here summarize data indicating that the estrogen-related receptors (ERRs) α and γ prevent bone formation. Inhibiting these receptors may thus constitute an anabolic approach by increasing bone formation.

Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I.

Science.gov (United States)

Heppner, Jonathan M; Zaucke, Frank; Clarke, Lorne A

2015-02-01

Progressive skeletal and connective tissue disease represents a significant clinical burden in all of the mucopolysaccharidoses. Despite the introduction of enzyme replacement strategies for many of the mucopolysaccharidoses, symptomatology related to bone and joint disease appears to be recalcitrant to current therapies. In order to address these unmet medical needs a clearer understanding of skeletal and connective tissue disease pathogenesis is required. Historically the pathogenesis of the mucopolysaccharidoses has been assumed to directly relate to progressive storage of glycosaminoglycans. It is now apparent for many lysosomal storage disorders that more complex pathogenic mechanisms underlie patients' clinical symptoms. We have used proteomic and genome wide expression studies in the murine mucopolysaccharidosis I model to identify early pathogenic events occurring in micro-dissected growth plate tissue. Studies were conducted using 3 and 5-week-old mice thus representing a time at which no obvious morphological changes of bone or joints have taken place. An unbiased iTRAQ differential proteomic approach was used to identify candidates followed by validation with multiple reaction monitoring mass spectrometry and immunohistochemistry. These studies reveal significant decreases in six key structural and signaling extracellular matrix proteins; biglycan, fibromodulin, PRELP, type I collagen, lactotransferrin, and SERPINF1. Genome-wide expression studies in embryonic day 13.5 limb cartilage and 5 week growth plate cartilage followed by specific gene candidate qPCR studies in the 5week growth plate identified fourteen significantly deregulated mRNAs (Adamts12, Aspn, Chad, Col2a1, Col9a1, Hapln4, Lum, Matn1, Mmp3, Ogn, Omd, P4ha2, Prelp, and Rab32). The involvement of biglycan, PRELP and fibromodulin; all members of the small leucine repeat proteoglycan family is intriguing, as this protein family is implicated in the pathogenesis of late onset osteoarthritis

Bone thickness of the infrazygomatic crest area in skeletal Class III growing patients: A computed tomographic study

International Nuclear Information System (INIS)

Lee, Hyub Soo; Choi, Hang Moon; Choi, Dong Soon; Jang, Insan; Cha, Bong Kuen

2013-01-01

This study was performed to investigate the bone thickness of the infrazygomatic crest area by computed tomography (CT) for placement of a miniplate as skeletal anchorage for maxillary protraction in skeletal Class III children. CT images of skeletal Class III children (7 boys, 9 girls, mean age: 11.4 years) were taken parallel to the Frankfurt horizontal plane. The bone thickness of the infrazygomatic crest area was measured at 35 locations on the right and left sides, perpendicular to the bone surface. The bone was thickest (5.0 mm) in the upper zygomatic bone and thinnest (1.1 mm) in the anterior wall of the maxillary sinus. Generally, there was a tendency for the bone to be thicker at the superior and lateral area of the zygomatic process of the maxilla. There was no clinically significant difference in bone thickness between the right and left sides; however, it was thicker in male than in female subjects. In the infrazygomatic crest area, the superior and lateral area of the zygomatic process of the maxilla had the most appropriate thickness for placement of a miniplate in growing skeletal Class III children with a retruded maxilla.

Bone thickness of the infrazygomatic crest area in skeletal Class III growing patients: A computed tomographic study

Energy Technology Data Exchange (ETDEWEB)

Lee, Hyub Soo; Choi, Hang Moon; Choi, Dong Soon; Jang, Insan; Cha, Bong Kuen [College of Dentistry and Research Institute of Oral Science, Gangneung-Wonju National University, Gangneung (Korea, Republic of)

2013-12-15

This study was performed to investigate the bone thickness of the infrazygomatic crest area by computed tomography (CT) for placement of a miniplate as skeletal anchorage for maxillary protraction in skeletal Class III children. CT images of skeletal Class III children (7 boys, 9 girls, mean age: 11.4 years) were taken parallel to the Frankfurt horizontal plane. The bone thickness of the infrazygomatic crest area was measured at 35 locations on the right and left sides, perpendicular to the bone surface. The bone was thickest (5.0 mm) in the upper zygomatic bone and thinnest (1.1 mm) in the anterior wall of the maxillary sinus. Generally, there was a tendency for the bone to be thicker at the superior and lateral area of the zygomatic process of the maxilla. There was no clinically significant difference in bone thickness between the right and left sides; however, it was thicker in male than in female subjects. In the infrazygomatic crest area, the superior and lateral area of the zygomatic process of the maxilla had the most appropriate thickness for placement of a miniplate in growing skeletal Class III children with a retruded maxilla.

Value of skeletal scintiscanning in cases of primary bone tumours and tumourous alterations

International Nuclear Information System (INIS)

Sokolowski, U.

1982-01-01

In the course of an investigation on the storage behaviour of primary bone tumours and tumourous bone alterations the skeletal scintigrams of a total of 26 patients were evaluated. Bone scintiscanning was done according to current practice after injection of an average amount of 10mCi sup(99m)Tc-MDP, followed by a semiquantitative evaluation. In all cases of malignant bone tumours there was fond to be increased storage of radionuclide; with benign bone alterations this was so in 70 per cent of cases. To differentiate between benign and malignant tumours respectively inflammatory bone diseases was not as a rule possible; however, the investigation yielded additional information completing the X-ray findings essentially. Thus very high storage of radioactivity was established for all osteosarcomas, whereas benign bone growths exhibited more circumscribed accumulations of activity. Skeletal scintiscanning for diagnostical purposes is particularly informative as to the early detection of bone foci evading X-ray diagnosis, more accurate delimitation of tumourous processes, and course control of tumours tending to degenerate. (orig./MG) [de

Hyoid bone position and head posture comparison in skeletal Class I and Class II subjects: A retrospective cephalometric study

Directory of Open Access Journals (Sweden)

Pawankumar Dnyandeo Tekale

2014-01-01

Full Text Available Objective: The aim of the study was to investigate the hyoid bone position and the head posture using lateral cephalograms in subjects with skeletal Class I and skeletal Class II pattern and to investigate the gender differences. Materials and Methods: The study used lateral cephalograms of 40 subjects (20 skeletal Class I pattern; 20 skeletal Class II pattern. Lateral cephalograms were traced and analyzed for evaluation of the hyoid bone position and the head posture using 34 parameters. Independent sample t-test was performed to compare the differences between the two groups and between genders in each group. Statistical tests were performed using NCSS 2007 software (NCSST, Kaysville, Utah, USA. Results: The linear measurements between the hyoid bone (H and cervical spine (CV2ia, the nasion-sella line, palatal line nasion line, the anterior nasal spine (ANS to perpendicular projection of H on the NLP (NLP- Nasal Linear Projection (H-NLP/ANS as well as the posterior cranial points (Bo, Ar and S points were found to be less in skeletal Class II subjects. The measurement H-CV2ia was found to be less in males with skeletal Class I pattern and H-CV4ia was found to be less in males with skeletal Class II pattern. The natural head posture showed no significant gender differences. Conclusion: The position of hyoid bone was closer to the cervical vertebra horizontally in skeletal Class II subjects when compared with skeletal Class I subjects. In males, the hyoid bone position was closer to the cervical vertebra horizontally both in skeletal Class I and skeletal Class II subjects.

Hydatid disease of bone: a mimic of other skeletal pathologies

International Nuclear Information System (INIS)

Morris, B.S.; Garg, A.; Chavhan, G.B.; Madiwale, C.V.

2002-01-01

Skeletal hydatidosis results from the deposition of the larval form of the Echinococcus, a genus of tapeworm. The incidence of bone disease is extremely low as most larvae are trapped by the liver and lung upon release of the embryo into the portal blood stream. The interpretation of imaging studies can prove very confusing because bone changes evolve with time, and the non-specificity of these findings often leads to a mistaken diagnosis. We present the case of a 35-year-old woman with long-standing pain in the left hip joint in which the findings on CT were thought of as being either tuberculous or neoplastic in nature. The result of a CT-guided biopsy and another done following surgery concurred on an unexpected diagnosis of a hydatid cyst. This case illustrates that in the absence of a high index of suspicion for echinococcal infection, the semblance of imaging findings of hydatid disease in bone to those of other skeletal pathologies can lead to misinterpretation. Copyright (2002) Blackwell Science Pty Ltd

Impact of skeletal unloading on bone formation: Role of systemic and local factors

Science.gov (United States)

Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

Phenotypic Dissection of Bone Mineral Density Reveals Skeletal Site Specificity and Facilitates the Identification of Novel Loci in the Genetic Regulation of Bone Mass Attainment

NARCIS (Netherlands)

J.P. Kemp (John); M.C. Medina-Gomez (Carolina); K. Estrada Gil (Karol); B. St Pourcain (Beate); D.H.M. Heppe (Denise); N.M. Warrington (Nicole); L. Oei (Ling); S.M. Ring (Susan); C.J. Kruithof (Claudia); N.J. Timpson (Nicholas); L.E. Wolber (Lisa); S. Reppe (Sjur); K.M. Gautvik (Kaare); E. Grundberg (Elin); B. Ge (Bing); B.C.J. van der Eerden (Bram); J. van de Peppel (Jeroen); M.A. Hibbs (Matthew); C.L. Ackert-Bicknell (Cheryl); K. Choi (Kunho); D.L. Koller (Daniel); M.J. Econs (Michael); F.M. Williams (Frances); T. Foroud (Tatiana); M.C. Zillikens (Carola); C. Ohlsson (Claes); A. Hofman (Albert); A.G. Uitterlinden (André); G. Davey-Smith (George); V.W.V. Jaddoe (Vincent); J.H. Tobias (Jon); F. Rivadeneira Ramirez (Fernando); D.M. Evans (David)

2014-01-01

textabstractHeritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we

Skeletal muscle fat content is inversely associated with bone strength in young girls.

Science.gov (United States)

Farr, Joshua N; Funk, Janet L; Chen, Zhao; Lisse, Jeffrey R; Blew, Robert M; Lee, Vinson R; Laudermilk, Monica; Lohman, Timothy G; Going, Scott B

2011-09-01

Childhood obesity is an established risk factor for metabolic disease. The influence of obesity on bone development, however, remains controversial and may depend on the pattern of regional fat deposition. Therefore, we examined the associations of regional fat compartments of the calf and thigh with weight-bearing bone parameters in girls. Data from 444 girls aged 9 to 12 years from the Jump-In: Building Better Bones study were analyzed. Peripheral quantitative computed tomography (pQCT) was used to assess bone parameters at metaphyseal and diaphyseal sites of the femur and tibia along with subcutaneous adipose tissue (SAT, mm(2) ) and muscle density (mg/cm(3) ), an index of skeletal muscle fat content. As expected, SAT was positively correlated with total-body fat mass (r = 0.87-0.89, p  .05), except the distal tibia (β = 0.09, p = .03). In conclusion, skeletal muscle fat content of the calf and thigh is inversely associated with weight-bearing bone strength in young girls. Copyright © 2011 American Society for Bone and Mineral Research.

N-terminal pro-C-type natriuretic peptide in serum associated with bone destruction in patients with multiple myeloma

DEFF Research Database (Denmark)

Mylin, Anne K; Goetze, Jens P; Heickendorff, Lene

2015-01-01

AIM: To examine whether N-terminal proCNP concentrations in serum is associated with bone destruction in patients with multiple myeloma. MATERIALS & METHODS: N-terminal proCNP and biochemical bone markers were measured in 153 patients. Radiographic bone disease and skeletal-related events were...

Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent.

Science.gov (United States)

Horiuchi-Suzuki, Kazuko; Konno, Aya; Ueda, Mayumi; Fukuda, Yoko; Nishio, Saori; Hashimoto, Kazuyuki; Saji, Hideo

2004-03-01

In spite of recent advances in bone cellular and molecular biology, there is still a poor correlation between these parameters and data obtained from bone scintigraphy. Diphosphonate derivatives radiolabelled with technetium-99m (Tc-BPs) have long been recognised as bone-seeking agents with an affinity for areas of active mineralisation. However, during clinical trials with a pH-sensitive tumour agent, the pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] showed a noticeable osteotropic character only in bone pathologies (bone metastases, Paget's diseases) and lacked accumulation in normal mature bone. To decipher the osteotropic character of Tc(V)-DMS, a study at the cellular level was considered necessary. Moreover, to learn more about the role of Tc bone agents, acid-base regulation by bone tissue or cells was studied. First, biological parameters in body fluid were measured under systemic acidosis, induced by glucose administration, in normal and Ehrlich ascites tumour (EAT)-bearing mice. Then, in vivo biodistribution studies using Tc(V)-DMS or a conventional Tc-BP agent were carried out. The effect of glucose-mediated acidification on the skeletal distribution of the Tc agents in the mice provided valuable hints regarding the differential mediation of bone cells in skeletal tissue affinity for the agents. Thereafter, in vitro studies on osteoblast and osteoclast cells were performed and the comparative affinity of Tc(V)-DMS and Tc-BP was screened under diverse acidification conditions. Moreover, studies were also carried out on acid-base parameters related to the cellular uptake mechanism. Very specific pH-sensitive Tc(V)-DMS accumulation only in the osteoclastic system was detected, and use of Tc(V)-DMS in the differential detection of osteoblastic and osteoclastic metastases is discussed.

Suspected fetal skeletal malformations or bone diseases: how to explore

International Nuclear Information System (INIS)

Cassart, Marie

2010-01-01

Skeletal dysplasias are a heterogeneous and complex group of conditions that affect bone growth and development and result in various anomalies in shape and size of the skeleton. Although US has proved reliable for the prenatal detection of skeletal abnormalities, the precise diagnosis of a dysplasia is often difficult to make before birth (especially in the absence of a familial history) due to their various phenotypic presentations, the variability in the time at which they manifest and often, the lack of precise molecular diagnosis. In addition to the accuracy of the antenatal diagnosis, it is very important to establish a prognosis. This is a clinically relevant issue as skeletal dysplasias may be associated with severe disability and may even be lethal. We will therefore describe the respective role of two-dimensional (2-D) US, three-dimensional (3-D) US and CT in the antenatal assessment of skeletal malformations. (orig.)

Age-related changes in bone in the dog: calcium homeostasis

International Nuclear Information System (INIS)

Williams, E.A.; Kelly, P.J.

1984-01-01

To explore the changes in the relationship between skeletal and Ca 2+ homeostasis with age, a study was made of 50 dogs divided into four age groups. The skeletal uptake of 85 Sr decreased markedly with age, and the immunoreactive parathyroid hormone (iPTH) level increased. There was a significant correlation between iPTH value and the calculated short-term exchange of Ca in bone. Bone formation and bone resorption decreased with age except that in the oldest group of dogs the resorption increased. The authors suggest that in aging dogs the skeletal exchange of Ca falls to a very low level that decreases the immediate effect of PTH and thus leads to a chronic net increase in circulating PTH. Concomitant with this is an increase in osteoclastic bone resorption and, over a long time, loss of skeletal mass

Skeletal Aging and Osteoporosis Biomechanics and Mechanobiology

CERN Document Server

2013-01-01

The focus of this book is on mechanical aspects of skeletal fragility related to aging and osteoporosis. Topics include: Age-related changes in trabecular structure and strength; age-related changes in cortical material properties; age-related changes in whole-bone structure; predicting bone strength and fracture risk using image-based methods and finite element analysis; animal models of osteoporosis and aging; age-related changes in skeletal mechano responsiveness; exercise and physical interventions for osteoporosis.

Cost-effectiveness Analysis of Denosumab in the Prevention of Skeletal-related Events in Patients with Prostate Cancer in Kazakhstan

Directory of Open Access Journals (Sweden)

Carina Bektur

2014-12-01

Full Text Available Introduction. Bone mass loss (BML is one of the adverse effects of oncological chemotherapy, especially in cases of hormonal types of cancer, such as a prostate cancer (PC. BML is strongly associated with skeletal-related events (SREs, therefore decreasing the quality of patient’s life. Denosumab shows an advantage over zoledronic acid (ZA in delaying the first onset of SREs and subsequent SREs in adults with PC in several phase III clinical trials. Since generic ZA recently became available, the purpose of the present study was to assess the cost-effectiveness of denosumab vs. brand or generic ZA in the prevention of SREs in Kazakhstani patients with PC.Methods. A Markov model was constructed in Tree-Age Pro 2013 software program with 4-week model cycles to analyze the cost-effectiveness of the treatments from the perspective of Ministry of Health (MoH over a 10-year PC cohort. Direct costs (in Kazakhstani monetary units “tenge” in 2014 included costs of drug, SRE (pathologic fracture, surgery to bone, radiation to bone, spinal cord compression, and adverse events treatment. All costs were discounted for 3% per year. Effectiveness was appraised based on the number of SREs. Health states were defined according to SRE occurrence, SRE history, and death. The model assumed that a maximum of 1 SRE could occur in each cycle. Transition probabilities were derived from the relevant phase III trials. Results were present in the incremental total cost per SRE avoided. One-way sensitivity analyses were performed to examine the robustness of the model.Results. Over the 10-year period, denosumab incurred 103,091 tenge higher costs than brand ZA, 677,133 tenge higher costs than generic ZA, and 0.58 fewer SREs per patient with PC. The estimated incremental total direct costs per SRE avoided with the use of denosumab were 177,743 tenge (instead of brand ZA and 1,167,470 tenge (instead of generic ZA. Results were robust to one-way sensitivity analyses

Cone-beam computed tomography evaluation of dental, skeletal, and alveolar bone changes associated with bonded rapid maxillary expansion

Directory of Open Access Journals (Sweden)

Namrata Dogra

2016-01-01

Full Text Available Aims and Objectives: To evaluate skeletal changes in maxilla and its surrounding structures, changes in the maxillary dentition and maxillary alveolar bone changes produced by bonded rapid maxillary expansion (RME using cone-beam computed tomography (CBCT. Materials and Methods: The sample consisted of 10 patients (6 males and 4 females with age range 12 to 15 years treated with bonded RME. CBCT scans were performed at T1 (pretreatment and at T2 (immediately after expansion to evaluate the dental, skeletal, and alveolar bone changes. Results: RME treatment increased the overall skeletal parameters such as interorbital, zygomatic, nasal, and maxillary widths. Significant increases in buccal maxillary width was observed at first premolar, second premolar, and first molar level. There was a significant increase in arch width both on the palatal side and on the buccal side. Significant tipping of right and left maxillary first molars was seen. There were significant reductions in buccal bone plate thickness and increase in palatal bone plate thickness. Conclusions: Total expansion achieved with RME was a combination of dental, skeletal and alveolar bone changes. At the first molar level, 28.45% orthopedic, 16.03% alveolar bone bending, and 55.5% orthodontic changes were observed.

Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases secondary to advanced renal cell carcinoma: application to France, Germany, and the United Kingdom.

Science.gov (United States)

Botteman, M F; Meijboom, M; Foley, I; Stephens, J M; Chen, Y M; Kaura, S

2011-12-01

The use of zoledronic acid (ZOL) has recently been shown to significantly reduce the risk of new skeletal-related events (SREs) in renal cell carcinoma (RCC) patients with bone metastases. The present exploratory study assessed the cost-effectiveness of ZOL in this population, adopting a French, German, and United Kingdom (UK) government payer perspective. This cost-effectiveness model was based on a post hoc retrospective analysis of a subset of patients with RCC who were included in a larger randomized clinical trial of patients with bone metastases secondary to a variety of cancers. In the trial, patients were randomized to receive ZOL (n = 27) or placebo (n = 19) with concomitant antineoplastic therapy every 3 weeks for 9 months (core study) plus 12 months during a study extension. Since the trial did not collect costs or data on the quality-adjusted life years (QALYs) of the patients, these outcomes had to be assumed via modeling exercises. The costs of SREs were estimated using hospital DRG tariffs. These estimates were supplemented with literature-based costs where possible. Drug, administration, and supply costs were obtained from published and internet sources. Consistent with similar economic analyses, patients were assumed to experience quality of life decrements lasting 1 month for each SRE. Uncertainty surrounding outcomes was addressed via multivariate sensitivity analyses. Patients receiving ZOL experienced 1.07 fewer SREs than patients on placebo. Patients on ZOL experienced a gain in discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (-€ 4,196 in France, - € 3,880 in Germany, and -€ 3,355 in the UK). After taking into consideration the drug therapy costs, ZOL saved € 1,358, € 1,223, and € 719 in France, Germany, and the UK, respectively. In the multivariate sensitivity analyses, therapy with ZOL saved costs in 67

Biology of Bone: The Vasculature of the Skeletal System.

Science.gov (United States)

Watson, Emma C; Adams, Ralf H

2017-09-11

Blood vessels are essential for the distribution of oxygen, nutrients, and immune cells, as well as the removal of waste products. In addition to this conventional role as a versatile conduit system, the endothelial cells forming the innermost layer of the vessel wall also possess important signaling capabilities and can control growth, patterning, homeostasis, and regeneration of the surrounding organ. In the skeletal system, blood vessels regulate developmental and regenerative bone formation as well as hematopoiesis by providing vascular niches for hematopoietic stem cells. Here we provide an overview of blood vessel architecture, growth and properties in the healthy, aging, and diseased skeletal system. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Age-related changes in the global skeletal uptake of technetium-99m methylene diphosphonate in healthy women

International Nuclear Information System (INIS)

Carnevale, V.; Frusciante, V.; Scillitani, A.; Modoni, S.; Pileri, M.; Chiodini, I.; Dicembrino, F.; Romagnoli, E.; Minisola, S.

1996-01-01

A short-term evaluation of global skeletal uptake (GSU) of technetium-99m methylene diphosphonate (MDP) was performed in 40 healthy female subjects with a wide age range in order to investigate the clinical performance of the technique and to detect the age-related changes in bone turnover. The results obtained were compared with measurements of the main biochemical markers of skeletal metabolism. We found that GSU increases progressively with age, independently of concomitant changes in renal function; significant correlations with biochemical markers of bone formation were also found. Therefore, the method appears to provide useful information concerning the bone turnover rate, and is also applicable to elderly people owing to its simplicity. (orig.). With 4 figs., 2 tabs

MT1-MMP and type II collagen specify skeletal stem cells and their bone and cartilage progeny

DEFF Research Database (Denmark)

Szabova, L.; Yamada, S.S.; Wimer, H.

2009-01-01

-expressing cells of the skeleton rescues not only diminished chondrocyte proliferation, but surprisingly, also results in amelioration of the severe skeletal dysplasia associated with MT1-MMP deficiency through enhanced bone formation. Consistent with this increased bone formation, type II collagen was identified...... from nontransgenic MT1-MMP-deficient littermates. These observations show that type II collagen is not stringently confined to the chondrocyte but is expressed in skeletal stem/progenitor cells (able to regenerate bone, cartilage, myelosupportive stroma, marrow adipocytes) and in the chondrogenic...

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis.

Science.gov (United States)

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D; Davies, John E; Stanford, William L

2016-05-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance--replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. ©AlphaMed Press.

Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

DEFF Research Database (Denmark)

Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.

2003-01-01

OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystopl......OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment...... mass ex vivo.RESULTS: Most (90%) of the rats survived the study period (8 months); six rats died from bowel obstruction at the level of the entero-anastomosis and four had to be killed because of persistent severe diarrhoea. Vital intestinal mucosa was found in all augmented bladders. There were...... no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P

Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

Science.gov (United States)

Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

2018-01-01

There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

Two Cases of Sternal 'Cold' Lesions on Bone Imaging in the Metastatic Skeletal Disease

Energy Technology Data Exchange (ETDEWEB)

Park, Hyung Gun; Seo, Bong Kwan; Lee, Hoon Yong; Lee, Myung Chul; Choi, Sung Jae; Kim, Noe Kyeong; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1983-09-15

Traditionally, a positive bone scan shows single or multiple areas of increased uptake in them metastatic skeletal disease. The occurrence of 'cold' lytic-like or photon-deficient lesions in bone imaging is probably uncommon. Photon-deficient focus or cold lesion of the sternum was demonstrated on {sup 99m}Tc-MDP bone imaging in 2 individuals with acute myeloid leukemia and primary hepatoma, respectively.

Role of Thyroid Hormones in Skeletal Development and Bone Maintenance.

Science.gov (United States)

Bassett, J H Duncan; Williams, Graham R

2016-04-01

The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art.

The diagnostic value of PSA, cPSA and bone scintigraphy for early skeletal metastasis of prostate cancer

International Nuclear Information System (INIS)

Xue Zhongguang

2007-01-01

Objective: To evaluate the value of prostate specific antigen (PSA), complexed prostate specific antigen (cPSA) and bone scintigraphic imaging in diagnosis of early skeletal metastasis of prostate cancer. Methods: 152 patients (74 with prostate cancer, 78 with benign prostate disease) and 90 controls were examined for the serum concentrations of PSA and cPSA. At the same time, the 74 patients with PCa were examined with bone scintigraphy. The cPSA/PSA ratio was calculated. Results: Serum PSA, cPSA levels and cPSA/PSA ratio of patients with prostate cancer were significantly higher than those in benign prostate patients and controls. In addition, the serum PSA, cPSA levels and cPSA/PSA ratio in prostate cancer patients with skeletal metastasis were remarkably higher than those in patients without skeletal metastasis, and the differences were significant (P 20 μg/L, cPSA>10 μg/L, cPSA/PSA>0.80, there is a high probability that skeletal metastasis of prostate cancer would be present and bone scintigraphy should be performed. (authors)

The role of the SIBLING, Bone Sialoprotein in skeletal biology - Contribution of mouse experimental genetics.

Science.gov (United States)

Bouleftour, Wafa; Juignet, Laura; Bouet, Guenaelle; Granito, Renata Neves; Vanden-Bossche, Arnaud; Laroche, Norbert; Aubin, Jane E; Lafage-Proust, Marie-Hélène; Vico, Laurence; Malaval, Luc

2016-01-01

Bone Sialoprotein (BSP) is a member of the "Small Integrin-Binding Ligand N-linked Glycoproteins" (SIBLING) extracellular matrix protein family of mineralized tissues. BSP has been less studied than other SIBLING proteins such as Osteopontin (OPN), which is coexpressed with it in several skeletal cell types. Here we review the contribution of genetically engineered mice (BSP gene knockout and overexpression) to the understanding of the role of BSP in the bone organ. The studies made so far highlight the role of BSP in skeletal mineralization, as well as its importance for proper osteoblast and osteoclast differentiation and activity, most prominently in primary/repair bone. The absence of BSP also affects the local environment of the bone tissue, in particular hematopoiesis and vascularization. Interestingly, lack of BSP induces an overexpression of OPN, and the cognate protein could be responsible for some aspects of the BSP gene knockout skeletal phenotype, while replacing BSP for some of its functions. Such interplay between the partly overlapping functions of SIBLING proteins, as well as the network of cross-regulations in which they are involved should now be the focus of further work. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Trabecular bone score as a skeletal fragility index in acromegaly patients.

Science.gov (United States)

Hong, A R; Kim, J H; Kim, S W; Kim, S Y; Shin, C S

2016-03-01

Lumbar spine trabecular bone score (TBS) was significantly decreased in active acromegaly patients. TBS may be useful to assess the skeletal fragility in acromegaly in which bone mineral density (BMD) is not sufficient to represent bone strength and explain the high incidence of fragility fractures in acromegaly patients. Although the data on BMD are controversial, patients with acromegaly have an increased risk of fragility fracture. We examined the lumbar spine TBS to explain the skeletal deterioration in acromegaly patients. We included 14 men and 19 women acromegaly patients who underwent dual-energy X-ray absorptiometry at the time of diagnosis from 2000 to 2014 at Seoul National University Hospital. Ninety-nine age-, sex- and body mass index-matched controls were recruited. Biochemical parameters, lumbar spine TBS, and BMD at all sites were measured. Gonadal status was evaluated at diagnosis. Lumbar spine TBS was lower in acromegaly patients than in controls in both genders (1.345 ± 0.121 vs. 1.427 ± 0.087, P = 0.005 in men; 1.356 ± 0.082 vs. 1.431 ± 0.071, P = 0.001 in women). In contrast, BMD at all sites did not differ between the two groups. Hypogonadal acromegaly patients (men, n = 9; women, n = 12) had lower TBS values compared with controls both in men and women (all P acromegaly patients, lumbar spine TBS was lower than in women controls only (P = 0.041). Skeletal microarchitecture was deteriorated in acromegaly patients as assessed by TBS, which seems to be a consequence of growth hormone excess as well as hypogonadism, especially in women.

Skeletal stem cell and bone implant interactions are enhanced by LASER titanium modification

Energy Technology Data Exchange (ETDEWEB)

Sisti, Karin E., E-mail: karinellensisti@gmail.com [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Federal University of Mato Grosso do Sul (UFMS), Campo Grande (Brazil); Andrés, María C. de; Johnston, David [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Almeida-Filho, Edson; Guastaldi, Antonio C. [Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Oreffo, Richard O.C. [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom)

2016-05-06

Purpose: To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs{sup 1}). Methods: Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1{sup +} hSSC{sup 1} function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb{sup 2}), ii) machined Ti surface group in osteogenic media (Mo{sup 3}), iii) LASER-modified Ti group in basal media (Lb{sup 4}) and, iv) LASER-modified Ti group in osteogenic media (Lo{sup 5}). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP{sup 6}) specific activity), live/dead immunostaining (Cell Tracker Green (CTG{sup 7})/Ethidium Homodimer-1 (EH-1{sup 8})), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype. Results: Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs{sup 1} on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP{sup 6} specific activity on the hSSCs{sup 1}-seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP{sup 6} and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated. Conclusions: LASER-modified Ti surfaces modify the behaviour of hSSCs.{sup 1} In particular, SSC{sup 1} adhesion, osteogenic gene expression, cell

Skeletal fluorosis in relation to drinking water in rural areas of West Azerbaijan, Iran.

Science.gov (United States)

Mohammadi, Ali Akbar; Yousefi, Mahmood; Yaseri, Mehdi; Jalilzadeh, Mohsen; Mahvi, Amir Hossein

2017-12-11

Skeletal fluorosis resulting from high fluoride level in drinking water is a major public health problem. The present study evaluated the association between exposures to drinking water fluoride and skeletal fluorosis in 5 villages of Poldasht County, Iran. All the data and information on the prevalence of bone diseases were obtained from the Health Record Department, Poldasht Health Centre. To obtain the odds ratio of bone disease problem in different risk factors, when considering the cluster effect of rural area, logistic regression in a multilevel model was used. Results showed that skeletal fluorosis of people who live in areas with high fluoride concentration is 18.1% higher than that of individuals who live in areas with low fluoride concentration. Skeletal fluorosis (54.5%) was observed in the age group of 71 years and above, and was more commonly found in females than males. According to Unadjusted, individuals who consume ≤3 unit milk and dairy products per week have almost the same level of bone diseases as compared to those that consume more than 3 units. This study indicated that, skeletal fluorosis is a general health problem in these rural areas because the results revealed that high percentage of the studied population had symptoms of skeletal fluorosis.

Comparison of whole body MR diffusion weighted imaging and skeletal scintigraphy in detecting bone metastasis

International Nuclear Information System (INIS)

Xu Xian; Ma Lin; Zhang Jinshan; Cai Youquan; Cheng Liuquan; Guo Xinggao; Xu Baixuan

2008-01-01

Objective: To evaluate the application of whole body MR diffusion weighted imaging (DWI) in the detection of bone metastasis using skeletal scintigraphy as the reference. Methods: Forty-two healthy volunteers and 38 patients with malignant tumors were enrolled in our study. All the patients received MR examination and skeletal scintigraphy within one week. MR examination was performed on GE signa 3.0T MR scanner using a build-in body coil. The skeletal system was divided into eight regions and the images of the whole body MR DWI and skeletal scintigraphy were reviewed to compare the two modalities patient by patient and region by region. The images were reviewed separately by two radiologists and two nuclear medicine physicians, who were blinded to the results of another imaging modality. Results: A total of 169 metastatic lesions in 69 regions of 30 patients were detected by whole body MR DWI while 156 lesions in 68 regions of 29 patients were identified by skeletal scintigraphy. There were two cases negative in scintigraphy but positive in whole body MR DWI and one case positive in scintigraphy only. There were eight lesions negative in scintigraphy but positive in whole body MR DWI, mainly located in the spine, pelvis and femur. Seven lesions were only detected by scintigraphy, mainly located in the skull, sternum, clavicle and scapula. Conclusion: The whole body MR DWI reveals excellent consistency with skeletal scintigraphy regarding bone metastasis, and the two modalities are complementary for each other. (authors)

Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system.

Science.gov (United States)

Gutch, Manish; Philip, Rajeev; Philip, Renjit; Toms, Ajit; Saran, Sanjay; Gupta, K K

2013-10-01

Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

Science.gov (United States)

Hinton, Pamela S

2016-08-01

Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

Age-related changes in vertebral and iliac crest 3D bone microstructure--differences and similarities.

Science.gov (United States)

Thomsen, J S; Jensen, M V; Niklassen, A S; Ebbesen, E N; Brüel, A

2015-01-01

Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes. The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between the bone microstructure at these skeletal sites. Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19-96 years) and 39 men (23-95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified. For both women and men, bone volume per total volume (BV/TV), connectivity density (CD), and trabecular number (Tb.N) decreased significantly, while structure model index (SMI) and trabecular separation (Tb.Sp) increased significantly with age at either skeletal site. Vertebral trabecular thickness (Tb.Th) was independent of age for both women and men, while iliac Tb.Th decreased significantly with age for men, but not for women. In general, the vertebral and iliac age-related changes were similar. The 95th percentile of the Tb.Th distribution increased significantly with age for women but was independent of age for men at the vertebral body, while it was independent of age for either sex at the iliac crest. The Tb.Th probability density functions at the two skeletal sites became significantly more similar with age for women, but not for men. The microstructural parameters at the iliac crest and the vertebral bodies were only moderately correlated from r = 0.38 for SMI in women to r = 0.75 for Tb.Sp in men. Age-related changes in vertebral and iliac bone microstructure were in general similar. The iliac

Prospective study of serial 18F-FDG PET and 18F-fluoride (18F-NaF) PET to predict time to skeletal related events, time-to-progression, and survival in patients with bone-dominant metastatic breast cancer.

Science.gov (United States)

Peterson, Lanell M; O'Sullivan, Janet; Wu, Qian Vicky; Novakova-Jiresova, Alena; Jenkins, Isaac; Lee, Jean H; Shields, Andrew; Montgomery, Susan; Linden, Hannah M; Gralow, Julie R; Gadi, Vijayakrishna K; Muzi, Mark; Kinahan, Paul E; Mankoff, David A; Specht, Jennifer M

2018-05-10

Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial 18 F-FDG PET was predictive of time to skeletal related events (tSRE) and time-to-progression (TTP). 18 F-NaF PET improves bone metastasis detection compared to bone scans. We prospectively tested 18 F-FDG PET and 18 F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (BD MBC). Methods: Patients with BD MBC were imaged with 18 F-FDG PET and 18 F-NaF PET prior to starting new therapy (scan1) and again at a range of times centered around approximately 4 months later (scan2). SUV max and SULpeak were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and 18 F-FDG PET and 18 F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) criteria were also applied. Survival curves for mPERCIST compared response categories of Complete Response+Partial Response+Stable Disease versus Progressive Disease (CR+PR+SD vs PD) for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher FDG SULpeak at scan2 predicted shorter time to tSRE ( P = PET mPERCIST, tSRE and TTP were longer in responders (CR, PR, or stable) compared to non-responders (PD) ( P = 0.007, 0.028 respectively), with a trend toward improved survival ( P = 0.1). An increase in the uptake between scans of up to 5 lesions by 18 F-NaF PET was associated with longer OS ( P = 0.027). Conclusion: Changes in 18 F-FDG PET parameters during therapy are predictive of tSRE and TTP, but not OS. mPERCIST evaluation in bone lesions may be useful in assessing response to therapy and is worthy of evaluation in multicenter, prospective trials. Serial 18 F-NaF PET was associated with OS, but was not useful for predicting TTP or tSRE in BD MBC

A clinical study evaluating bone mineral mass in the radius during skeletal growth

International Nuclear Information System (INIS)

Hagino, Hiroshi

1989-01-01

Using 125-I single photon absorptiometry, bone mineral measurements were performed on 206 healthy Japanese children (2 to 19 years of age). Bone mineral content (BMC), bone width (BW) and BMC/BW values were determined for the radius at distal 1/6 site (metaphysis) and distal 1/3 site (diaphysis). BMC/BW values at both sites correlated well with body height and weight. Bone mass in the diaphysis (distal 1/3 site) increased linearly during the 2-19 years of skeletal growth, but bone mass in the metaphysis (1/6 site) increased steeply during the pubertal period. In children receiving glucocorticoid therapy, bone mass was reduced in proportion to the duration of drug administration. In children under anticonvulsant therapy, the yearly increse in bone mass was significantly low especially in those patients with poor physical activity levels. Bone mineral decrease in the radius occurred in the children with hypopituitalism, hypothyroidism (cretinism), hyperthyroidism and Turner's syndrome. (author)

Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system

Directory of Open Access Journals (Sweden)

Manish Gutch

2013-01-01

Full Text Available Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

Concise review: bridging the gap: bone regeneration using skeletal stem cell-based strategies-where are we now?

DEFF Research Database (Denmark)

Dawson, Jonathan I; Kanczler, Janos; Kassem, Moustapha

2014-01-01

Skeletal stem cells confer to bone its innate capacity for regeneration and repair. Bone regeneration strategies seek to harness and enhance this regenerative capacity for the replacement of tissue damaged or lost through congenital defects, trauma, functional/esthetic problems, and a broad range...... for musculoskeletal regeneration. Stem Cells 2014;32:35-44...... of diseases associated with an increasingly aged population. This review describes the state of the field and current steps to translate and apply skeletal stem cell biology in the clinic and the problems therein. Challenges are described along with key strategies including the isolation and ex vivo expansion...

A Comparison of Hand Wrist Bone Analysis with Two Different Cervical Vertebral Analysis in Measuring Skeletal Maturation

OpenAIRE

Pichai, Saravanan; Rajesh, M; Reddy, Naveen; Adusumilli, Gopinath; Reddy, Jayaprakash; Joshi, Bhavana

2014-01-01

Background: Skeletal maturation is an integral part of individual pattern of growth and development and is a continuous process. Peak growth velocity in standing height is the most valid representation of the rate of overall skeletal growth. Ossification changes of hand wrist and cervical vertebrae are the reliable indicators of growth status of individual. The objective of this study was to compare skeletal maturation as measured by hand wrist bone analysis and cervical vertebral analysis. M...

Low-Dose, Ionizing Radiation and Age-Related Changes in Skeletal Microarchitecture

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Joshua S. Alwood

2012-01-01

Full Text Available Osteoporosis can profoundly affect the aged as a consequence of progressive bone loss; high-dose ionizing radiation can cause similar changes, although less is known about lower doses (≤100 cGy. We hypothesized that exposure to relatively low doses of gamma radiation accelerates structural changes characteristic of skeletal aging. Mice (C57BL/6J-10 wk old, male were irradiated (total body; 0-sham, 1, 10 or 100 cGy 137Cs and tissues harvested on the day of irradiation, 1 or 4 months later. Microcomputed tomography was used to quantify microarchitecture of high turnover, cancellous bone. Irradiation at 100 cGy caused transient microarchitectural changes over one month that were only evident at longer times in controls (4 months. Ex vivo bone cell differentiation from the marrow was unaffected by gamma radiation. In conclusion, acute ionizing gamma irradiation at 100 cGy (but not at 1 cGy or 10 cGy exacerbated microarchitectural changes normally found during progressive, postpubertal aging prior to the onset of age-related osteoporosis.

Bone morphogenetic protein-induced heterotopic bone formation: What have we learned from the history of a half century?

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Takenobu Katagiri, PhD

2015-05-01

Full Text Available Bone morphogenetic protein (BMP was originally discovered by Marshall Urist a half century ago following the observation of a unique activity that induced heterotopic bone formation in skeletal muscle tissue. The molecular mechanisms underlying the induction of heterotopic bone formation in skeletal muscle by BMPs were elucidated through the purification and molecular cloning of BMPs and identification of their functional receptors and downstream effectors, as well as from genetic disorders related to BMP activity. BMPs are important regulators of not only skeletal development and regeneration but also the homeostasis of normal skeletal muscle mass. There is still much to learn about the physiology and pathology at the interface of BMPs and skeletal muscle.

[Morphological analysis of alveolar bone of anterior mandible in high-angle skeletal class II and class III malocclusions assessed with cone-beam computed tomography].

Science.gov (United States)

Ma, J; Jiang, J H

2018-02-18

To evaluate the difference of features of alveolar bone support under lower anterior teeth between high-angle adults with skeletal class II malocclusions and high-angle adults presenting skeletal class III malocclusions by using cone-beam computed tomography (CBCT). Patients who had taken the images of CBCT were selected from the Peking University School and Hospital of Stomatology between October 2015 and August 2017. The CBCT archives from 62 high-angle adult cases without orthodontic treatment were divided into two groups based on their sagittal jaw relationships: skeletal class II and skeletal class III. vertical bone level (VBL), alveolar bone area (ABA), and the width of alveolar bone were measured respectively at the 2 mm, 4 mm, 6 mm below the cemento-enamel junction (CEJ) level and at the apical level. After that, independent samples t-tests were conducted for statistical comparisons. The ABA of the mandibular alveolar bone in the area of lower anterior teeth was significantly thinner in the patients of skeletal class III than those of skeletal class II, especially in terms of the apical ABA, total ABA on the labial and lingual sides and the ABA at 6 mm below CEJ level on the lingual side (Pclass III than those of skeletal class II, especially regarding the apical level on the labial and lingual side and at the level of 4 mm, 6 mm below CEJ level on the lingual side (Pclass III adult patients with high-angle when compared with the sample of high-angle skeletal class II adult cases. We recommend orthodontists to be more cautious in treatment of high-angle skeletal class III patients, especially pay attention to control the torque of lower anterior teeth during forward and backward movement, in case that the apical root might be absorbed or fenestration happen in the area of lower anterior teeth.

Age-related variation in limb bone diaphyseal structure among Inuit foragers from Point Hope, northern Alaska.

Science.gov (United States)

Wallace, I J; Nesbitt, A; Mongle, C; Gould, E S; Grine, F E

2014-01-01

Age-related deterioration of limb bone diaphyseal structure is documented among precontact Inuit foragers from northern Alaska. These findings challenge the concept that bone loss and fracture susceptibility among modern Inuit stem from their transition away from a physically demanding traditional lifestyle toward a more sedentary Western lifestyle. Skeletal fragility is rare among foragers and other traditional-living societies, likely due to their high physical activity levels. Among modern Inuit, however, severe bone loss and fractures are apparently common. This is possibly because of recent Western influences and increasing sedentism. To determine whether compromised bone structure and strength among the Inuit are indeed aberrant for a traditional-living group, data were collected on age-related variation in limb bone diaphyseal structure from a group predating Western influences. Skeletons of 184 adults were analyzed from the Point Hope archaeological site. Mid-diaphyseal structure was measured in the humerus, radius, ulna, femur, and tibia using CT. Structural differences were assessed between young, middle-aged, and old individuals. In all bones examined, both females and males exhibited significant age-related reductions in bone quantity. With few exceptions, total bone (periosteal) area did not significantly increase between young and old age in either sex, nor did geometric components of bending rigidity (second moments of area). While the physically demanding lifestyles of certain traditional-living groups may protect against bone loss and fracture susceptibility, this is not the case among the Inuit. It remains possible, however, that Western characteristics of the modern Inuit lifestyle exacerbate age-related skeletal deterioration.

Sex-specific patterns in cortical and trabecular bone microstructure in the Kirsten Skeletal Collection, South Africa.

Science.gov (United States)

Beresheim, Amy C; Pfeiffer, Susan K; Grynpas, Marc D; Alblas, Amanda

2018-02-07

The purpose of this study was to provide bone histomorphometric reference data for South Africans of the Western Cape who likely dealt with health issues under the apartheid regime. The 206 adult individuals ( n female = 75, n male = 131, mean = 47.9 ± 15.8 years) from the Kirsten Skeletal Collection, U. Stellenbosch, lived in the Cape Town metropole from the late 1960s to the mid-1990s. To study age-related changes in cortical and trabecular bone microstructure, photomontages of mid-thoracic rib cross-sections were quantitatively examined. Variables include relative cortical area (Rt.Ct.Ar), osteon population density (OPD), osteon area (On.Ar), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp). All cortical variables demonstrated significant relationships with age in both sexes, with women showing stronger overall age associations. Peak bone mass was compromised in some men, possibly reflecting poor nutritional quality and/or substance abuse issues throughout adolescence and early adulthood. In women, greater predicted decrements in On.Ar and Rt.Ct.Ar suggest a structural disadvantage with age, consistent with postmenopausal bone loss. Age-related patterns in trabecular bone microarchitecture are variable and difficult to explain. Except for Tb.Th, there are no statistically significant relationships with age in women. Men demonstrate significant negative correlations between BV/TV, Tb.N, and age, and a significant positive correlation between Tb.Sp and age. This research highlights sex-specific differences in patterns of age-related bone loss, and provides context for discussion of contemporary South African bone health. While the study sample demonstrates indicators of poor bone quality, osteoporosis research continues to be under-prioritized in South Africa. © 2018 Wiley Periodicals, Inc.

Isolation and culture of primary osteocytes from the long bones of skeletally mature and aged mice

Science.gov (United States)

Stern, Amber Rath; Stern, Matthew M.; Van Dyke, Mark E.; Jähn, Katharina; Prideaux, Matthew; Bonewald, Lynda F.

2013-01-01

The purpose of this work was to establish a methodology to enable the isolation and study of osteocytes from skeletally mature young (4-month-old) and old (22-month-old) mice. The location of osteocytes deep within bone is ideal for their function as mechanosensors. However, this location makes the observation and study of osteocytes in vivo technically difficult. Osteocytes were isolated from murine long bones through a process of extended collagenase digestions combined with EDTA-based decalcification. A tissue homogenizer was used to reduce the remaining bone fragments to a suspension of bone particles, which were placed in culture to yield an outgrowth of osteocyte-like cells. All of the cells obtained from this outgrowth that displayed an osteocyte-like morphology stained positive for the osteocyte marker E11/GP38.[Q1] The osteocyte phenotype was further confirmed by a lack of staining for alkaline phosphatase and the absence of collagen1a1 expression. The outgrowth of osteocytes also expressed additional osteocyte-specific genes such as Sost and Mepe. This technique facilitates the isolation of osteocytes from skeletally mature bone. This novel enabling methodology should prove useful in advancing our understanding of the roles mature osteocytes play in bone health and disease. PMID:22668415

Radiographic assessment of skeletal maturation stages for orthodontic patients: hand-wrist bones or cervical vertebrae?

Science.gov (United States)

Lai, Eddie Hsiang-Hua; Liu, Jen-Pei; Chang, Jenny Zwei-Chieng; Tsai, Shih-Jaw; Yao, Chung-Chen Jane; Chen, Mu-Hsiung; Chen, Yi-Jane; Lin, Chun-Pin

2008-04-01

The skeletal maturation status of a growing patient can influence the selection of orthodontic treatment procedures. Either lateral cephalometric or hand-wrist radiography can be used to assess skeletal development. In this study, we examined the correlation between the maturation stages of cervical vertebrae and hand-wrist bones in Taiwanese individuals. The study group consisted of 330 male and 379 female subjects ranging in age from 8 to 18 years. A total of 709 hand-wrist and 709 lateral cephalometric radiographs were analyzed. Hand-wrist maturation stages were assessed using National Taiwan University Hospital Skeletal Maturation Index (NTUH-SMI). Cervical vertebral maturation stages were determined by the latest Cervical Vertebral Maturation Stage (CVMS) Index. Spearman's rank correlation was used to correlate the respective maturation stages assessed from the hand-wrist bones and the cervical vertebrae. The values of Spearman's rank correlation were 0.910 for males and 0.937 for females, respectively. These data confirmed a strong and significant correlation between CVMS and NTUH-SMI systems (p less than 0.001). After comparison of the mean ages of subjects in different stages of CVMS and NTU-SMI systems, we found that CVMS I corresponded to NTUH-SMI stages 1 and 2, CVMS II to NTUH-SMI stage 3, CVMS III to NTUHSMI stage 4, CVMS IV to NTUH-SMI stage 5, CVMS V to NTUH-SMI stages 6, 7 and 8, and CVMS VI to NTUH-SMI stage 9. Our results indicate that cervical vertebral maturation stages can be used to replace hand-wrist bone maturation stages for evaluation of skeletal maturity in Taiwanese individuals.

Bone turnover markers are correlated with total skeletal uptake of 99mTc-methylene diphosphonate (99mTc-MDP)

International Nuclear Information System (INIS)

Lenora, Janaka; Norrgren, Kristina; Thorsson, Ola; Wollmer, Per; Obrant, Karl J; Ivaska, Kaisa K

2009-01-01

Skeletal uptake of 99m Tc labelled methylene diphosphonate ( 99m Tc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99m Tc-MDP. 22 postmenopausal women (52–80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99m Tc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC). The median TSU of 99m Tc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density. In conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99m Tc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption

Exercise Preserves Physical Function in Prostate Cancer Patients with Bone Metastases.

Science.gov (United States)

Galvão, Daniel A; Taaffe, Dennis R; Spry, Nigel; Cormie, Prue; Joseph, David; Chambers, Suzanne K; Chee, Raphael; Peddle-McIntyre, Carolyn J; Hart, Nicolas H; Baumann, Freerk T; Denham, James; Baker, Michael; Newton, Robert U

2018-03-01

The presence of bone metastases has excluded participation of cancer patients in exercise interventions and is a relative contraindication to supervised exercise in the community setting because of concerns of fragility fracture. We examined the efficacy and safety of a modular multimodal exercise program in prostate cancer patients with bone metastases. Between 2012 and 2015, 57 prostate cancer patients (70.0 ± 8.4 yr; body mass index, 28.7 ± 4.0 kg·m) with bone metastases (pelvis, 75.4%; femur, 40.4%; rib/thoracic spine, 66.7%; lumbar spine, 43.9%; humerus, 24.6%; other sites, 70.2%) were randomized to multimodal supervised aerobic, resistance, and flexibility exercises undertaken thrice weekly (EX; n = 28) or usual care (CON; n = 29) for 3 months. Physical function subscale of the Medical Outcomes Study Short-Form 36 was the primary end point as an indicator of patient-rated physical functioning. Secondary end points included objective measures of physical function, lower body muscle strength, body composition, and fatigue. Safety was assessed by recording the incidence and severity of any adverse events, skeletal complications, and bone pain throughout the intervention. There was a significant difference between groups for self-reported physical functioning (3.2 points; 95% confidence interval, 0.4-6.0 points; P = 0.028) and lower body muscle strength (6.6 kg; 95% confidence interval, 0.6-12.7; P = 0.033) at 3 months favoring EX. However, there was no difference between groups for lean mass (P = 0.584), fat mass (P = 0.598), or fatigue (P = 0.964). There were no exercise-related adverse events or skeletal fractures and no differences in bone pain between EX and CON (P = 0.507). Multimodal modular exercise in prostate cancer patients with bone metastases led to self-reported improvements in physical function and objectively measured lower body muscle strength with no skeletal complications or increased bone pain. ACTRN12611001158954.

A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration

Directory of Open Access Journals (Sweden)

Bruce Milthorpe

2013-04-01

Full Text Available A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP and transforming growth factor beta (TGF-β exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use.

A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration

Science.gov (United States)

Green, David W.; Padula, Matthew P.; Santos, Jerran; Chou, Joshua; Milthorpe, Bruce; Ben-Nissan, Besim

2013-01-01

A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP) and transforming growth factor beta (TGF-β) exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use. PMID:23574983

Effects of Cremation on Fetal Bones.

Science.gov (United States)

Zana, Michela; Magli, Francesca; Mazzucchi, Alessandra; Castoldi, Elisa; Gibelli, Daniele; Caccia, Giulia; Cornacchia, Francesca; Gaudio, Daniel A; Mattia, Mirko; Cattaneo, Cristina

2017-09-01

The charring process is a weak point of anthropological analysis as it changes bone morphology and reduces information obtainable, specially in fetuses. This experiment aims at verifying the conservation of fetal bones after cremation. A total of 3138 fetuses of unknown sex and age were used, deriving from legal and therapeutic abortions from different hospitals of Milan. Cremations took place in modern crematoria. Nine cremation events were analyzed, each ranging from 57 to 915 simultaneously cremated fetuses. During the cremations, 4356 skeletal remains were recovered, 3756 of which (86.2%) were morphologically distinguishable. All types of fetal skeletal elements were found, with the exception of some cranial bones. Only 3.4% of individuals could be detected after the cremation process, because of the prevalence of abortions under 12 lunar weeks. All fire alterations were observed and the results were statistically analyzed. This pilot study confirmed the possibility of preservation of fetal skeletal elements after cremation. © 2017 American Academy of Forensic Sciences.

Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading.

Directory of Open Access Journals (Sweden)

Jason A Bleedorn

Full Text Available Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK, phosphatidylinositol 3-kinase (PI3K/protein kinase B (Akt, and mammalian target of rapamycin (mTOR. However, anabolic signaling responses to bone loading using a whole animal in vivo model have not been studied in detail. Therefore, we examined mechanically-induced signaling events at five time points from 0 to 24 hours after loading using the rat in vivo ulna end-loading model. Western blot analysis of bone for MAPK's, PI3K/Akt, and mTOR signaling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR to estimate gene expression of calcitonin gene-related protein alpha (CGRP-α, brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, c-jun, and c-fos in dorsal root ganglion (DRG of the brachial intumescence were performed. There was a significant increase in signaling through MAPK's including extracellular signal-related kinase (ERK and c-Jun N-terminal kinase (JNK in loaded limbs at 15 minutes after mechanical loading. Ulna loading did not significantly influence expression of the genes of interest in DRG neurons. Bone signaling and DRG gene expression from the loaded and contralateral limbs was correlated (SR>0.40, P<0.05. However, bone signaling did not correlate with expression of the genes of interest in DRG neurons. These results suggest that signaling through the MAPK pathway may be involved in load-induced bone formation in vivo. Further characterization of the

A comparison of hand wrist bone analysis with two different cervical vertebral analysis in measuring skeletal maturation.

Science.gov (United States)

Pichai, Saravanan; Rajesh, M; Reddy, Naveen; Adusumilli, Gopinath; Reddy, Jayaprakash; Joshi, Bhavana

2014-09-01

Skeletal maturation is an integral part of individual pattern of growth and development and is a continuous process. Peak growth velocity in standing height is the most valid representation of the rate of overall skeletal growth. Ossification changes of hand wrist and cervical vertebrae are the reliable indicators of growth status of individual. The objective of this study was to compare skeletal maturation as measured by hand wrist bone analysis and cervical vertebral analysis. Hand wrist radiographs and lateral cephalograms of 72 subjects aged between 7 and 16 years both male and female from the patients visiting Department of Orthodontics and Dentofacial Orthopedics, R.V. Dental College and Hospital. The 9 stages were reduced to 5 stages to compare with cervical vertebral maturation stage by Baccetti et al. The Bjork, Grave and Brown stages were reduced to six intervals to compare with cervical vertebral maturational index (CVMI) staging by Hassel and Farman. These measurements were then compared with the hand wrist bone analysis, and the results were statistically analyzed using the Mann-Whitney test. There was no significant difference between the hand wrist analysis and the two different cervical vertebral analyses for assessing skeletal maturation. There was no significant difference between the two cervical vertebral analyses, but the CVMI method, which is visual method is less time consuming. Vertebral analysis on a lateral cephalogram is as valid as the hand wrist bone analysis with the advantage of reducing the radiation exposure of growing subjects.

Unusual facies, arthrogryposis, advanced skeletal maturation and unique bone changes. A new congenital malformation syndrome

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Jequier, S.; Kozlowski, K.

1987-07-01

Two strikingly similar infant siblings showed the following pattern of anomalies: unusual cranio-facial appearance, arthrogryposis, advanced bone age of the hips and unique skeletal X-ray abnormalities. They represent a previously unrecognised, fatal malformation syndrome.

Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial.

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Loriot, Yohann; Miller, Kurt; Sternberg, Cora N; Fizazi, Karim; De Bono, Johann S; Chowdhury, Simon; Higano, Celestia S; Noonberg, Sarah; Holmstrom, Stefan; Mansbach, Harry; Perabo, Frank G; Phung, De; Ivanescu, Cristina; Skaltsa, Konstantina; Beer, Tomasz M; Tombal, Bertrand

2015-05-01

Enzalutamide significantly increased overall survival and radiographic progression-free survival compared with placebo in the PREVAIL trial of asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer. We report the effect of enzalutamide on health-related quality of life (HRQoL), pain, and skeletal-related events observed during this trial. In this phase 3, double-blind trial, patients were randomly assigned (1:1) to receive enzalutamide 160 mg/day (n=872) or placebo (n=845) orally. HRQoL was assessed at baseline and during treatment using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D questionnaires. Pain status was assessed at screening, baseline, week 13, and week 25 with the Brief Pain Inventory Short Form (BPI-SF). The primary analysis of HRQoL data used a mixed-effects model to test the difference between least square means change from baseline at week 61. We assessed change from baseline, percentage improvement, and time to deterioration in HRQoL and pain, the proportion of patients with a skeletal-related event, and time to first skeletal-related event. Analysis was done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01212991. Median treatment duration was 16·6 months (IQR 10·1-21·1) in the enzalutamide group and 4·6 months (2·8-9·7) in the placebo group. The mixed-effects model analyses showed significant treatment differences in change from baseline to week 61 with enzalutamide compared with placebo for most FACT-P endpoints and EQ-5D visual analogue scale. Median time to deterioration in FACT-P total score was 11·3 months (95% CI 11·1-13·9) in the enzalutamide group and 5·6 months (5·5-5·6) in the placebo groups (hazard ratio [HR] 0·62 [95% CI 0·54-0·72]; p<0·0001). A significantly greater proportion of patients in the enzalutamide group than in the placebo group reported clinically meaningful

Treatment of Bone Metastases with Radium-223 in Patients with Castration Resistant Prostate Cancer (CRPC): Alternative or Complementary to Innovative Molecular Therapies?

International Nuclear Information System (INIS)

Bombardieri, Emilio

2013-01-01

The skeletal metastatic disease is a real clinical problem. Approximately 70% of patients with prostate or breast cancer and 35% of those with advanced lung, thyroid, and kidney cancers will develop skeletal metastases, which cause considerable morbidity. Several options are available for treatment, to be used either alone or in various combinations: hormones in case of hormone-sensitive tumours, chemotherapy, biphosphonates, external beam radiation therapy, surgery (in pathologic or impending fracture), bone-seeking radiopharmceuticals, and also molecular therapies. Focusing our attention to patients with prostate cancer, 50% of patients with bone metastases develop skeletal related events (SREs) such as: severe pain, pathologic fractures, spinal compression syndrome, malignant hypercalcemia, bone marrow suppression. All these SREs require adequate therapy since generally determine several functional impairments and worsen the prognosis. It is well known that skeletal complications reduce the quality of life affecting different aspects, physical, functional end emotional. SREs are associated also with lower survival

Generalized skeletal pathology: Results of radionuclide studies

International Nuclear Information System (INIS)

Fueger, G.F.; Aigner, R.

1987-01-01

Generalized pathological changes may involve the skeleton systematically (bone tissue, bone marrow) or at multiple sites involving destruction or infiltration. Appropriate radionuclide studies include total-body bone or bone marrow scintigraphy, absorptiometry (osteodensitometry) and the 24 h whole-body retention measurement. Established radioindicators are 99m-Tc-(hydroxy)methylendiphosphonate (HMDP or MDP) and 99m-Tc-human serumalbumin-nanocolloid. Absorptiometry of the forearm, extended by computer-assisted transaxial tomography, may be expected to prove as the most efficient method of bone density measurement. The 24 h whole-body retention measurement is useful for the diagnosis and follow-up of metabolic and endocrine osteopathies, if the very same osteotropic 99m-Tc-chelate is used. Whole-body bone scintigraphy today is one of the most important radionuclide studies for diagnosis and follow-up of skeletal metastases. Scintigraphy provides evidence of skeletal metastases several months earlier than radiological examinations. In about 40 percent of patients with cancer of the prostate, scintigraphy provided positive findings of skeletal metastases in the absence of both pain and increased levels of phosphatase. In patients with a history of malignancy, 60 percent of solitary findings on skeletal scintigraphy are metastases. The frequency of false negative findings obtained by whole-body skeletal scintigraphy are metastases. The frequency of false negative findings obtained by whole-body skeletal scintigraphy ranges from 2 to 4%. Compared to skeletal scintigraphy, bone marrow scintigraphy frequently yields significant additional findings in cases of plasmocytoma, histiocytoma, lymphoma and haemoblastoses. (orig.) [de

An expression relating breaking stress and density of trabecular bone

DEFF Research Database (Denmark)

Rajapakse, C.S.; Thomsen, J.S.; Ortiz, J.S.E.

2004-01-01

Bone mineral density (BMD) is the principal diagnostic tool used in clinical settings to diagnose and monitor osteoporosis. Experimental studies on ex vivo bone samples from multiple skeletal locations have been used to propose that their breaking stress bears a power-law relationship to volumetric...

Skeletal Stem Cells: Origins, Functions and Uncertainties.

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Mohamed, Fatma F; Franceschi, Renny T

2017-12-01

The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

A Comparison of Hand Wrist Bone Analysis with Two Different Cervical Vertebral Analysis in Measuring Skeletal Maturation

Science.gov (United States)

Pichai, Saravanan; Rajesh, M; Reddy, Naveen; Adusumilli, Gopinath; Reddy, Jayaprakash; Joshi, Bhavana

2014-01-01

Background: Skeletal maturation is an integral part of individual pattern of growth and development and is a continuous process. Peak growth velocity in standing height is the most valid representation of the rate of overall skeletal growth. Ossification changes of hand wrist and cervical vertebrae are the reliable indicators of growth status of individual. The objective of this study was to compare skeletal maturation as measured by hand wrist bone analysis and cervical vertebral analysis. Materials and Methods: Hand wrist radiographs and lateral cephalograms of 72 subjects aged between 7 and 16 years both male and female from the patients visiting Department of Orthodontics and Dentofacial Orthopedics, R.V. Dental College and Hospital. The 9 stages were reduced to 5 stages to compare with cervical vertebral maturation stage by Baccetti et al. The Bjork, Grave and Brown stages were reduced to six intervals to compare with cervical vertebral maturational index (CVMI) staging by Hassel and Farman. These measurements were then compared with the hand wrist bone analysis, and the results were statistically analyzed using the Mann–Whitney test. Results: There was no significant difference between the hand wrist analysis and the two different cervical vertebral analyses for assessing skeletal maturation. There was no significant difference between the two cervical vertebral analyses, but the CVMI method, which is visual method is less time consuming. Conclusion: Vertebral analysis on a lateral cephalogram is as valid as the hand wrist bone analysis with the advantage of reducing the radiation exposure of growing subjects. PMID:25395791

Multiple myeloma: radiology or bone scanning

International Nuclear Information System (INIS)

Leonard, R.C.F.; Owen, J.P.; Proctor, S.J.; Hamilton, P.J.

1981-01-01

A comparative study of radionuclide bone scanning and skeletal radiology in patients with multiple myeloma revealed four principal findings: (i) There were no cases of negative bone scans with positive skeletal radiographs. (ii) Lytic bone lesions were seriously underestimated by bone scans. (iii) Bone scans tended to pick up lesions in ribs missed on the skeletal surveys. (iv) Patients with bone pain were more likely to have positive bone scans and skeletal radiographs than asymptomatic patients. (author)

1H MR spectroscopy of skeletal muscle, liver and bone marrow

International Nuclear Information System (INIS)

Machann, Juergen; Stefan, Norbert; Schick, Fritz

2008-01-01

Proton magnetic resonance spectroscopy ( 1 H MRS) offers interesting metabolic information even from organs outside the brain. In the first part, applications in skeletal muscle for determination of intramyocellular lipids (IMCL), which are involved in the pathogenesis of insulin resistance, are described. Peculiarities of spectral pattern are discussed and studies for short-term regulation of IMCL, as dietary intervention, exercise and fasting are presented. The second part deals with quantification of small amounts of lipids in the liver (hepatic lipids, HL), which is also of increasing interest in the field of diabetes research. Recommendations for correct assessment of spectra in this 'moving organ' are given and the importance of HL is described by examples of a cohort at increased risk for type 2 diabetes. Regulation of HL is described on the basis of a few studies. The third part concentrates on spectral characterization of bone marrow. Peripheral bone marrow of adults consists mainly of fat, while central marrow regions in the pelvis, spinal column and breast bone (and the peripheral bone marrow of children as well) contribute to blood formation and show a variable composition of adipocytes (fat cells), interstitial fluid and water containing precursor cells for erythrocytes, leucocytes and thrombocytes. Adapted 1 H spectroscopic techniques allow a semi-quantitative analysis of bone marrow composition

Skeletal MR imaging: Correlation with skeletal scintigraphy

International Nuclear Information System (INIS)

Colletti, P.M.; Raval, J.K.; Ford, P.V.; Benson, R.C.; Kerr, R.M.; Boswell, W.D.; Siegel, M.E.; Ralls, P.W.

1987-01-01

Skeletal MR images bone marrow while skeletal scintigraphy uses bone metabolism to demonstrate abnormalities. The purpose of this paper is to correlate these MR and scintigraphic findings. T1 and T2 MR images at 0.5 T were correlated with planar bone scintigraphy (RN) using Tc-99m MDP in 56 patients. Of 23 cases with suspected spinal metastases, 19 were positive by MR imaging, 16 by RN. Individual lesions were shown better by MR imaging in five and by RN in two. These two cases had scoliosis, a potential difficulty with MR imaging. In 14 cases of suspected avascular necrosis (AVN), MR imaging was positive in 13 while RN was positive in ten. One negative case by RN had bilateral AVN by MR imaging. Four skull lesions shown easily by RN were seen only in retrospect on MR images. MR imaging is advantageous in evaluating bones with predominant marrow such as vertebrae or the femoral head, while RN is superior in areas primarily composed of cortical bone such as the skull

Mechanisms of internal emitter skeletal toxicity

International Nuclear Information System (INIS)

Jee, W.S.S.

1985-01-01

The purpose of this program is to determine the mechanisms for the induction of skeletal cancers in dogs and man by α-emitting bone-seeking radionuclides from the nuclear fuel cycle. The role of microdistribution of radium-226 and plutonium-239, bone metabolism, bone cell turnover, and localized bone cell dosimetry in bone can induction will be determined. The osteogenic cell dose will be measured in dogs to develop better quantitative dose response information. Skeletal carcinogenesis models will be developed by correlating the local dosimetry, tumor site and incidence, age-dependent skeletal biology (bone morphometry, bone cell at risk, bone cell turnover, residence time and fate, remodeling rate, growth pattern and rate, hormonal influences, manipulation of bone cell populations of the bone modeling and remodeling systems, etc.). The authors will test the hypothesis that the frequency of osteosarcomas is proportional to the average dose delivered to cells at risk. They will also attempt to explain experimentally found toxicity ratios between volume- and bone surface-seeking radionuclides on the basis of radiation dose ratios

Clinical study evaluating bone mineral mass in the radius during skeletal growth. Single photon absorptiometry

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Hagino, Hiroshi

1989-01-01

Using 125-I single photon absorptiometry, bone mineral measurements were performed on 206 healthy Japanese children (2 to 19 years of age). Bone mineral content (BMC), bone width (BW) and BMC/BW values were determined for the radius at distal 1/6 site (metaphysis) and distal 1/3 site (diaphysis). BMC/BW values at both sites correlated well with body height and weight. Bone mass in the diaphysis (distal 1/3 site) increased linearly during the 2-19 years of skeletal growth, but bone mass in the metaphysis (1/6 site) increased steeply during the pubertal period. In children receiving glucocorticoid therapy, bone mass was reduced in proportion to the duration of drug administration. In children under anticonvulsant therapy, the yearly increse in bone mass was significantly low especially in those patients with poor physical activity levels. Bone mineral decrease in the radius occurred in the children with hypopituitalism, hypothyroidism (cretinism), hyperthyroidism and Turner's syndrome.

The Central Nervous System and Bone Metabolism: An Evolving Story.

Science.gov (United States)

Dimitri, Paul; Rosen, Cliff

2017-05-01

Our understanding of the control of skeletal metabolism has undergone a dynamic shift in the last two decades, primarily driven by our understanding of energy metabolism. Evidence demonstrating that leptin not only influences bone cells directly, but that it also plays a pivotal role in controlling bone mass centrally, opened up an investigative process that has changed the way in which skeletal metabolism is now perceived. Other central regulators of bone metabolism have since been identified including neuropeptide Y (NPY), serotonin, endocannabinoids, cocaine- and amphetamine-regulated transcript (CART), adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast differentiation, proliferation and function. The sympathetic nervous system was originally identified as the predominant efferent pathway mediating central signalling to control skeleton metabolism, in part regulated through circadian genes. More recent evidence points to a role of the parasympathetic nervous system in the control of skeletal metabolism either through muscarinic influence of sympathetic nerves in the brain or directly via nicotinic receptors on osteoclasts, thus providing evidence for broader autonomic skeletal regulation. Sensory innervation of bone has also received focus again widening our understanding of the complex neuronal regulation of bone mass. Whilst scientific advance in this field of bone metabolism has been rapid, progress is still required to understand how these model systems work in relation to the multiple confounders influencing skeletal metabolism, and the relative balance in these neuronal systems required for skeletal growth and development in childhood and maintaining skeletal integrity in adulthood.

Rapid-throughput skeletal phenotyping of 100 knockout mice identifies 9 new genes that determine bone strength.

Directory of Open Access Journals (Sweden)

J H Duncan Bassett

Full Text Available Osteoporosis is a common polygenic disease and global healthcare priority but its genetic basis remains largely unknown. We report a high-throughput multi-parameter phenotype screen to identify functionally significant skeletal phenotypes in mice generated by the Wellcome Trust Sanger Institute Mouse Genetics Project and discover novel genes that may be involved in the pathogenesis of osteoporosis. The integrated use of primary phenotype data with quantitative x-ray microradiography, micro-computed tomography, statistical approaches and biomechanical testing in 100 unselected knockout mouse strains identified nine new genetic determinants of bone mass and strength. These nine new genes include five whose deletion results in low bone mass and four whose deletion results in high bone mass. None of the nine genes have been implicated previously in skeletal disorders and detailed analysis of the biomechanical consequences of their deletion revealed a novel functional classification of bone structure and strength. The organ-specific and disease-focused strategy described in this study can be applied to any biological system or tractable polygenic disease, thus providing a general basis to define gene function in a system-specific manner. Application of the approach to diseases affecting other physiological systems will help to realize the full potential of the International Mouse Phenotyping Consortium.

Comparison of radiological changes in humans and beagles with skeletal deposits of radium

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Morgan, J P [Univ. of California, Davis; Pool, R R; Kirsh, I E

1983-01-01

At the Laboratory for Energy-related Health Research at the University of California, Davis, semimonthly injections of /sup 226/Ra were given to a group of beagle dogs, and periodic skeletal radiography followed, as well as histological studies of the bones. At the Center for Human Radiobiology measurements were made of radium body content in 2259 occupationally or otherwise exposed persons. Of these, 1768 had skeletal radiography (one or more times). In humans, the radiographic changes were, in decreasing order of frequency, osteolytic cortical and cancellous bone destruction, bone sclerosis, pathological fracture, and avascular necrosis of bone. In beagles, osteolytic destruction and pathological fractures were common, avascular necrosis was not observed, but there was frequently cortical thickening and new-bone formation in cancellous bone. In both population groups, there was a high incidence of bone sarcoma. In the beagles, one high-dosage group numbering 38 dogs had 49 malignant bone tumors. Among the 2259 measured persons, there were 60 who had bone sarcoma, and 29 who had cancer of the mastoids or paranasal sinuses. No significant skeletal effects have been diagnosed radiologically in persons with systemic intakes of /sup 226/Ra or /sup 228/Ra below about 10 ..mu..Ci or with skeletal doses below about 100 rad. In humans, the lowest skeletal dose at which a bone sarcoma has been diagnosed is 890 rad, and the lowest intake associated with a bone sarcoma is 96 ..integral..Ci /sup 226/Ra or about 1.7 ..mu..Ci per kg body weight.

The skeletal endocannabinoid system: clinical and experimental insights.

Science.gov (United States)

Raphael, Bitya; Gabet, Yankel

2016-05-01

Recently, there has been a rapidly growing interest in the role of cannabinoids in the regulation of skeletal remodeling and bone mass, addressed in basic, translational and clinical research. Since the first publications in 2005, there are more than 1000 publications addressing the skeletal endocannabinoid system. This review focuses on the roles of the endocannabinoid system in skeletal biology via the cannabinoid receptors CB1, CB2 and others. Endocannabinoids play important roles in bone formation, bone resorption and skeletal growth, and are sometimes age, gender, species and strain dependent. Controversies in the literature and potential therapeutic approaches targeting the endocannabinoid system in skeletal disorders are also discussed.

Comparison of interradicular distances and cortical bone thickness in Thai patients with class I and class II skeletal patterns using cone-beam computed tomography

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Khumsarn, Nattida [Dental Division of Lamphun Hospital, Lamphun (Thailand); Patanaporn, Virush; Janhom, Apirum; Jotikasthira, Dhirawat [Faculty of Dentistry, Chiang Mai University, Chiang Mai (Thailand)

2016-06-15

This study evaluated and compared interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns, using cone-beam computed tomography (CBCT). Pretreatment CBCT images of 24 Thai orthodontic patients with Class I and Class II skeletal patterns were included in the study. Three measurements were chosen for investigation: the mesiodistal distance between the roots, the width of the buccolingual alveolar process, and buccal cortical bone thickness. All distances were recorded at five different levels from the cementoenamel junction (CEJ). Descriptive statistical analysis and t-tests were performed, with the significance level for all tests set at p<0.05. Patients with a Class II skeletal pattern showed significantly greater maxillary mesiodistal distances (between the first and second premolars) and widths of the buccolingual alveolar process (between the first and second molars) than Class I skeletal pattern patients at 10 mm above the CEJ. The maxillary buccal cortical bone thicknesses between the second premolar and first molar at 8 mm above the CEJ in Class II patients were likewise significantly greater than in Class I patients. Patients with a Class I skeletal pattern showed significantly wider mandibular buccolingual alveolar processes than did Class II patients (between the first and second molars) at 4, 6, and 8 mm below the CEJ. In both the maxilla and mandible, the mesiodistal distances, the width of the buccolingual alveolar process, and buccal cortical bone thickness tended to increase from the CEJ to the apex in both Class I and Class II skeletal patterns.

Comparison of interradicular distances and cortical bone thickness in Thai patients with class I and class II skeletal patterns using cone-beam computed tomography

International Nuclear Information System (INIS)

Khumsarn, Nattida; Patanaporn, Virush; Janhom, Apirum; Jotikasthira, Dhirawat

2016-01-01

This study evaluated and compared interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns, using cone-beam computed tomography (CBCT). Pretreatment CBCT images of 24 Thai orthodontic patients with Class I and Class II skeletal patterns were included in the study. Three measurements were chosen for investigation: the mesiodistal distance between the roots, the width of the buccolingual alveolar process, and buccal cortical bone thickness. All distances were recorded at five different levels from the cementoenamel junction (CEJ). Descriptive statistical analysis and t-tests were performed, with the significance level for all tests set at p<0.05. Patients with a Class II skeletal pattern showed significantly greater maxillary mesiodistal distances (between the first and second premolars) and widths of the buccolingual alveolar process (between the first and second molars) than Class I skeletal pattern patients at 10 mm above the CEJ. The maxillary buccal cortical bone thicknesses between the second premolar and first molar at 8 mm above the CEJ in Class II patients were likewise significantly greater than in Class I patients. Patients with a Class I skeletal pattern showed significantly wider mandibular buccolingual alveolar processes than did Class II patients (between the first and second molars) at 4, 6, and 8 mm below the CEJ. In both the maxilla and mandible, the mesiodistal distances, the width of the buccolingual alveolar process, and buccal cortical bone thickness tended to increase from the CEJ to the apex in both Class I and Class II skeletal patterns

Adaptation of the Skeletal System during Long-duration Spaceflight

Science.gov (United States)

Sibonga, Jean D.; Cavanagh, Peter R.; Lang, Thomas F.; LeBlanc, Adrian D.; Schneider, Victor S.; Shackelford, Linda C.; Smith, Scott M.; Vico, Laurence

2008-01-01

exceeds spaceflight exposure but for which the restoration of whole bone strength remains an open issue and may involve structural alteration; and 4. Display risk factors for bone loss -- such as the negative calcium balance and down-regulated calcium-regulating hormones in response to bone atrophy -- that can be compounded by the constraints of conducting mission operations (inability to provide essential nutrients and vitamins). The full characterization of the skeletal response to mechanical unloading in space is not complete. In particular, countermeasures used to date have been inadequate and it is not yet known whether more appropriate countermeasures can prevent the changes in bone that have been found in previous flights, knowledge gaps related to the effects of prolonged (greater than or equal to 6 months) space exposure and to partial gravity environments are substantial, and longitudinal measurements on crew members after spaceflight are required to assess the full impact on skeletal recovery.

Determinants of relative skeletal maturity in South African children.

Science.gov (United States)

Hawley, Nicola L; Rousham, Emily K; Johnson, William; Norris, Shane A; Pettifor, John M; Cameron, Noël

2012-01-01

The variation of skeletal maturity about chronological age is a sensitive indicator of population health. Age appropriate or advanced skeletal maturity is a reflection of adequate environmental and social conditions, whereas delayed maturation suggests inadequate conditions for optimal development. There remains a paucity of data, however, to indicate which specific biological and environmental factors are associated with advancement or delay in skeletal maturity. The present study utilises longitudinal data from the South African Birth to Twenty (Bt20) study to indentify predictors of relative skeletal maturity (RSM) in early adolescence. A total of 244 black South African children (n=131 male) were included in this analysis. Skeletal maturity at age 9/10 years was assessed using the Tanner and Whitehouse III RUS technique. Longitudinal data on growth, socio-economic position and pubertal development were entered into sex-specific multivariable general linear regression models with relative skeletal maturity (skeletal age-chronological age) as the outcome. At 9/10 years of age males showed an average of 0.66 years delay in skeletal maturation relative to chronological age. Females showed an average of 1.00 year delay relative to chronological age. In males, being taller at 2 years (pdetermining the rate of skeletal maturation during childhood independently of current stature. Copyright © 2011 Elsevier Inc. All rights reserved.

BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction.

Science.gov (United States)

Friedman, C D; Costantino, P D; Takagi, S; Chow, L C

1998-01-01

BoneSource-hydroxyapatite cement is a new self-setting calcium phosphate cement biomaterial. Its unique and innovative physical chemistry coupled with enhanced biocompatibility make it useful for craniofacial skeletal reconstruction. The general properties and clinical use guidelines are reviewed. The biomaterial and surgical applications offer insight into improved outcomes and potential new uses for hydroxyapatite cement systems.

Screening for skeletal metastases of the spine and pelvis: gradient echo opposed-phase MRI compared with bone scintigraphy

International Nuclear Information System (INIS)

Neumann, K.; Hosten, N.; Venz, S.

1995-01-01

Opposed-phase gradient echo (GRE) MRI at 0.5 T was compared with T1-weighted GRE MRI and bone scintigraphy regarding the detection of malignant bone marrow infiltrates of the spine and pelvis. Seventeen control patients and 41 patients with suspected skeletal metastases were studied with plain and gadolinium-enhanced MRI. In the control group only a vertebral haemangioma showed contrast enhancement, while all metastases (confirmed histologically or by follow-up) were enhancing. Opposed-phase surface coil MRI showed a significantly higher contrast-to-noise ratio of 56 metastases than T1-weighted images. In 28 patients body coil opposed-phase MRI detected more metastatic foci of the spine and pelvis than did bone scintigraphy (84 vs 56). No scintigraphically visualised lesion was missed by MRI. In conclusion, body coil gadolinium-enhanced opposed-phase GRE MRI may be applied as a screening method for skeletal metastases of the spine and pelvis at intermediate field strengths. (orig.)

Screening for skeletal metastases of the spine and pelvis: gradient echo opposed-phase MRI compared with bone scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Neumann, K. [Zentralinstitut fuer Roentgendiagnostik, Universitaetsklinikum Essen, Gesamthochschule Essen (Germany); Hosten, N. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Venz, S. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany)

1995-11-01

Opposed-phase gradient echo (GRE) MRI at 0.5 T was compared with T1-weighted GRE MRI and bone scintigraphy regarding the detection of malignant bone marrow infiltrates of the spine and pelvis. Seventeen control patients and 41 patients with suspected skeletal metastases were studied with plain and gadolinium-enhanced MRI. In the control group only a vertebral haemangioma showed contrast enhancement, while all metastases (confirmed histologically or by follow-up) were enhancing. Opposed-phase surface coil MRI showed a significantly higher contrast-to-noise ratio of 56 metastases than T1-weighted images. In 28 patients body coil opposed-phase MRI detected more metastatic foci of the spine and pelvis than did bone scintigraphy (84 vs 56). No scintigraphically visualised lesion was missed by MRI. In conclusion, body coil gadolinium-enhanced opposed-phase GRE MRI may be applied as a screening method for skeletal metastases of the spine and pelvis at intermediate field strengths. (orig.)

Bone mineral density, chemical composition and biomechanical properties of the tibia of female rats exposed to cadmium since weaning up to skeletal maturity.

Science.gov (United States)

Brzóska, M M; Majewska, K; Moniuszko-Jakoniuk, J

2005-10-01

The influence of exposure to cadmium (Cd) during skeletal development on the risk of bone fractures at the stage of skeletal maturity was investigated on a female rat model of human exposure. The tibias of rats treated with 1, 5 or 50 mg Cd/l in drinking water for 3, 6, 9 and 12 months (since weaning) were used. The exposure to Cd dose- and time-dependently influenced the tibia bone mineral density (BMD) and chemical composition. In skeletally matured animals, at each level of the exposure to Cd, the BMD at the whole tibia and its diaphysis as well as the percentage of minerals content in the bone, including the content of zinc, copper and iron, were decreased compared to control. Moreover, in the 50 mg Cd/l group, the percentage of organic components content increased. The Cd-induced changes, at all levels of exposure, resulted in weakening in the yield strength and fracture strength of the tibia (a three-point bending test of the diaphysis and compression test with vertical loading) of the skeletally matured females. A very important and clinically useful finding of this study is that a decrease (even by several percent) in the tibia BMD results in weakness in the bone biomechanical properties and that the BMD may predict the risk of its fracture at the exposure to Cd. Moreover, the results together with our previous findings seem to suggest that tibia, due to higher vulnerability of its diaphysis, compared to the femoral diaphysis, to damage by Cd may be more useful than femur to investigate the effect of Cd on the cortical bone. The present study revealed that a low exposure to Cd (1 mg Cd/l), corresponding to low human environmental exposure, during the skeletal development affects the tibia mineral status leading to weakening in its mechanical properties at the skeletal maturity. The findings allow for the conclusion that environmental exposure to Cd during childhood and adolescence may enhance the risk of low BMD and fractures at adulthood.

Scapular bone destruction: A case report of skeletal tuberculosis with a series of dynamic radiologic features

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Lan Lan

2015-09-01

Full Text Available Tuberculosis (TB is an extremely common opportunistic infection in human immunodeficiency virus (HIV-positive patients. Pulmonary TB is the most common manifestation while skeletal TB, especially with an involvement of flat bone like scapula, is quite rare. We report the first case scapular TB in an advanced AIDS individual who was initially considered as lymphoma because of the faulty interpretation of the positivity of PET/CT scan. In this article, we present a series of dynamic radiologic data and emphasize the differential diagnostic of skeletal TB.

Short Anabolic Peptides for Bone Growth.

Science.gov (United States)

Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

2016-07-01

Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth. © 2016 Wiley Periodicals, Inc.

Physiological role of growth factors and bone morphogenetic proteins in osteogenesis and bone fracture healing: а review

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S. Sagalovsky

2015-01-01

Full Text Available The repair of large bone defects remains a major clinical orthopedic challenge. Bone regeneration and fracture healing is a complex physiological mechanisms regulated by a large number of biologically active molecules. Multiple factors regulate this cascade of molecular events, which affects different stages in the osteoblast and chondroblast lineage during such processes as migration, proliferation, chemotaxis, differentiation, inhibition, and extracellular protein synthesis. A recent review has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to identification of many signaling molecules associated with formation of skeletal tissues, including a large family of growth factors (transforming growth factor-β and bone morphogenetic proteins, fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, platelet-derived growth factor, cytokines and interleukins. There is increasing evidence indicating that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and bone mineralization. A clear understanding of cellular and molecular pathways involved in fracture healing is not only critical for improvement of fracture treatments, but it may also enhance further our knowledge of mechanisms involved in skeletal growth and repair, as well as mechanisms of aging. This suggests that, in the future, they may play a major role in the treatment of bone disease and fracture repair.

Resistance Training in Type II Diabetes Mellitus: Impact on Areas of Metabolic Dysfunction in Skeletal Muscle and Potential Impact on Bone

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Richard J. Wood

2012-01-01

Full Text Available The prevalence of Type II Diabetes mellitus (T2DM is increasing rapidly and will continue to be a major healthcare expenditure burden. As such, identification of effective lifestyle treatments is paramount. Skeletal muscle and bone display metabolic and functional disruption in T2DM. Skeletal muscle in T2DM is characterized by insulin resistance, impaired glycogen synthesis, impairments in mitochondria, and lipid accumulation. Bone quality in T2DM is decreased, potentially due to the effects of advanced glycation endproducts on collagen, impaired osteoblast activity, and lipid accumulation. Although exercise is widely recognized as an important component of treatment for T2DM, the focus has largely been on aerobic exercise. Emerging research suggests that resistance training (strength training may impose potent and unique benefits in T2DM. The purpose of this review is to examine the role of resistance training in treating the dysfunction in skeletal muscle and the potential role for resistance training in treating the associated dysfunction in bone.

The skeletal system

NARCIS (Netherlands)

Nikkels, PGJ

2015-01-01

Skeletal dysplasias are a group of disorders with a disturbance in development and/or growth of cartilage and/or bone. Epiphysis, metaphysis, and diaphysis of long bones are affected in a generalized manner with or without involvement of membranous bone of the skull. A dysostosis affects one or some

Highly efficient DNA extraction method from skeletal remains

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Irena Zupanič Pajnič

2011-03-01

Full Text Available Background: This paper precisely describes the method of DNA extraction developed to acquire high quality DNA from the Second World War skeletal remains. The same method is also used for molecular genetic identification of unknown decomposed bodies in routine forensic casework where only bones and teeth are suitable for DNA typing. We analysed 109 bones and two teeth from WWII mass graves in Slovenia. Methods: We cleaned the bones and teeth, removed surface contaminants and ground the bones into powder, using liquid nitrogen . Prior to isolating the DNA in parallel using the BioRobot EZ1 (Qiagen, the powder was decalcified for three days. The nuclear DNA of the samples were quantified by real-time PCR method. We acquired autosomal genetic profiles and Y-chromosome haplotypes of the bones and teeth with PCR amplification of microsatellites, and mtDNA haplotypes 99. For the purpose of traceability in the event of contamination, we prepared elimination data bases including genetic profiles of the nuclear and mtDNA of all persons who have been in touch with the skeletal remains in any way. Results: We extracted up to 55 ng DNA/g of the teeth, up to 100 ng DNA/g of the femurs, up to 30 ng DNA/g of the tibias and up to 0.5 ng DNA/g of the humerus. The typing of autosomal and YSTR loci was successful in all of the teeth, in 98 % dekalof the femurs, and in 75 % to 81 % of the tibias and humerus. The typing of mtDNA was successful in all of the teeth, and in 96 % to 98 % of the bones. Conclusions: We managed to obtain nuclear DNA for successful STR typing from skeletal remains that were over 60 years old . The method of DNA extraction described here has proved to be highly efficient. We obtained 0.8 to 100 ng DNA/g of teeth or bones and complete genetic profiles of autosomal DNA, Y-STR haplotypes, and mtDNA haplotypes from only 0.5g bone and teeth samples.

Maintaining bone health in prostate cancer throughout the disease continuum.

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Saad, Fred; Eastham, James

2010-06-01

Prostate cancer (PC) is the most prevalent malignancy in men, with 604,506 new cases diagnosed yearly worldwide. Maintaining bone health is important during all stages of PC, including patients who experience bone loss from androgen-deprivation therapy and patients who develop bone metastases. Patients with bone metastases often experience severe bone pain and are at increased risk for potentially debilitating skeletal-related events. Bisphosphonates are a well-established treatment option for patients with bone metastases from solid tumors and bone lesions from multiple myeloma. Zoledronic acid (ZOL) is the only bisphosphonate (BP) that has been extensively studied in patients with castration-recurrent PC and is indicated for treating patients with bone metastases from PC in conjunction with standard antineoplastic therapy. This review will examine the breadth of evidence supporting a role for ZOL and emerging therapies in managing patients with PC throughout the disease continuum. 2010 Elsevier Inc. All rights reserved.

Low calcium-phosphate intakes modulate the low-protein diet-related effect on peak bone mass acquisition: a hormonal and bone strength determinants study in female growing rats.

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Fournier, C; Rizzoli, R; Ammann, P

2014-11-01

Peak bone mass acquisition is influenced by environmental factors including dietary intake. A low-protein diet delays body and skeletal growth in association with a reduction in serum IGF-1 whereas serum FGF21 is increased by selective amino acid deprivation. Calcium (Ca) and phosphorous (P) are also key nutrients for skeletal health, and inadequate intakes reduce bone mass accrual in association with calciotropic hormone modulation. Besides, the effect of calcium supplementation on bone mass in prepubertal children appears to be influenced by protein intake. To further explore the interaction of dietary protein and Ca-P intake on bone growth, 1-month-old female rats were fed with an isocaloric 10%, 7.5%, or 5% casein diet containing normal or low Ca-P for an 8-week period (6 groups). Changes in tibia geometry, mineral content, microarchitecture, strength, and intrinsic bone quality were analyzed. At the hormonal level, serum IGF-1, fibroblast growth factor 21 (FGF21), PTH, 1,25-dihydroxyvitamin D3 (calcitriol), and FGF23 were investigated as well as the Ghr hepatic gene expression. In normal dietary Ca-P conditions, bone mineral content, trabecular and cortical bone volume, and bone strength were lower in the 5% casein group in association with a decrease in serum IGF-1 and an increase in FGF21 levels. Unexpectedly, the low-Ca-P diet attenuated the 5% casein diet-related reduction of serum IGF-1 and Ghr hepatic gene expression, as well as the low-protein diet-induced decrease in bone mass and strength. However, this was associated with lower cortical bone material level properties. The low-Ca-P diet increased serum calcitriol but decreased FGF23 levels. Calcitriol levels positively correlated with Ghr hepatic mRNA levels. These results suggest that hormonal modulation in response to a low-Ca-P diet may modify the low-protein diet-induced effect on Ghr hepatic mRNA levels and consequently the impact of low protein intakes on IGF-1 circulating levels and skeletal

Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

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Annie Schmid-Alliana

2018-01-01

Full Text Available Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on surrounding bone tissue. Lastly, we detail therapies for bone metastases. Due to poor prognosis for patients, the strategies mainly aim at reducing the impact of skeletal-related events on patients’ quality of life. However, recent advances have led to a better understanding of molecular mechanisms underlying bone metastases progression, and therefore of novel therapeutic targets.

Enhanced Androgen Signaling With Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture

National Research Council Canada - National Science Library

Wiren, Kristine M; Jepsen, Karl

2006-01-01

.... We genetically engineered transgenic mice in which androgen receptor (AR) overexpression is skeletally targeted in two separate models to better understand the role of androgen signaling directly in bone...

Relative effectiveness of 239Pu and some other internal emitters for bone cancer induction in beagles

International Nuclear Information System (INIS)

Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Bruenger, F.W.; Jee, W.S.S.; Angus, W.

1994-01-01

The toxicity ratio (relative effectiveness per gray of average skeletal dose) has been estimated for bone cancer induction in beagles injected as young adults with a number of bone-seeking internal emitters. These experiments yielded calculated toxicity ratios (± SD) relative to 226 Ra = 1.0 of 239 Pu = 16 ± 5 (single exposure to monomeric Pu) and 32 ± 10 (continuous exposure from an extraskeletal deposit in the body), 224 Ra = 16 ± 5 (chronic exposure) and approximately 6 ± 2 (single exposure), 228 Th = 8.5 ± 2.3, 241 Am = 6 ± 0.8, 228 Ra = 2.0 ± 0.5, 249 Cf = 6 ± 3, 252 Cf = 4 ±2, 90 Sr = 1.0 ± 0.5 (for high doses) and 0.05 ± 0.03 (for low doses) and 0.01 ± 0.01 (for extremely low doses). Because no skeletal malignancies were observed among beagles given only 253 Es, the toxicity ratio is undefined. 43 refs., 2 tabs

Quantitative skeletal scintiscanning

International Nuclear Information System (INIS)

Haushofer, R.

1982-01-01

330 patients were examined by skeletal scintiscanning with sup(99m)Tc pyrophosphate and sup(99m)methylene diphosphonate in the years between 1977 and 1979. Course control examinations were carried out in 12 patients. The collective of patients presented with primary skeletal tumours, metastases, inflammatory and degenerative skeletal diseases. Bone scintiscanning combined with the ''region of interest'' technique was found to be an objective and reproducible technique for quantitative measurement of skeletal radioactivity concentrations. The validity of nuclear skeletal examinations can thus be enhanced as far as diagnosis, course control, and differential diagnosis are concerned. Quantitative skeletal scintiscanning by means of the ''region of interest'' technique has opened up a new era in skeletal diagnosis by nuclear methods. (orig./MG) [de

Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma

DEFF Research Database (Denmark)

Abildgaard, Niels; Brixen, K; Eriksen, E.F

2004-01-01

BACKGROUND AND OBJECTIVES: Bone lesions often occur in multiple myeloma (MM), but no tests have proven useful in identifying patients with increased risk. Bone marker assays and bone densitometry are non-invasive methods that can be used repeatedly at low cost. This study was performed to evaluate...... 6 weeks, DEXA-scans performed every 3 months, and skeletal radiographs were done every 6 months as well as when indicated. RESULTS: Serum ICTP and urinary NTx were predictive of progressive bone events. Markers of bone formation, bone mineral density assessments, and M component measurements were...... changes, and our data do not support routine use of sequential DEXA-scans. However, lumbar DEXA-scans at diagnosis can identify patients with increased risk of early vertebral collapses. Sequential analyses of serum ICTP and urinary NTx are useful for monitoring bone damage....

Archform comparisons between skeletal class II and III malocclusions.

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Wei Zou

Full Text Available The purpose of this cross-sectional research was to explore the relationship of the mandibular dental and basal bone archforms between severe Skeletal Class II (SC2 and Skeletal Class III (SC3 malocclusions. We also compared intercanine and intermolar widths in these two malocclusion types. Thirty-three virtual pretreatment mandibular models (Skeletal Class III group and Thirty-five Skeletal Class II group pretreatment models were created with a laser scanning system. FA (the midpoint of the facial axis of the clinical crownand WALA points (the most prominent point on the soft-tissue ridgewere employed to produce dental and basal bone archforms, respectively. Gained scatter diagrams of the samples were processed by nonlinear regression analysis via SPSS 17.0. The mandibular dental and basal bone intercanine and intermolar widths were significantly greater in the Skeletal Class III group compared to the Skeletal Class II group. In both groups, a moderate correlation existed between dental and basal bone arch widths in the canine region, and a high correlation existed between dental and basal bone arch widths in the molar region. The coefficient of correlation of the Skeletal Class III group was greater than the Skeletal Class II group. Fourth degree, even order power functions were used as best-fit functions to fit the scatter plots. The radius of curvature was larger in Skeletal Class III malocclusions compared to Skeletal Class II malocclusions (rWALA3>rWALA2>rFA3>rFA2. In conclusion, mandibular dental and basal intercanine and intermolar widths were significantly different between the two groups. Compared with Skeletal Class II subjects, the mandibular archform was more flat for Skeletal Class III subjects.

Recognition of fibrous dysplasia of bone mimicking skeletal metastasis on 18F-FDG PET/CT imaging

International Nuclear Information System (INIS)

Su, Ming Gang; Tian, Rong; Fan, Qiu Ping; Tian, Ye; Li, Fang Lan; Li, Lin; Kuang, An Ren; Miller, John Howard

2011-01-01

Fibrous dysplasia of bone (FDB) reveals intense 18F-FDG uptake mimicking metastases on 18F-FDG PET/CT. We reviewed sites of FDB revealed by 18F-FDG PET/CT imaging to allow identification of this abnormality. Eleven patients (7 male, 4 female, aged 16-78 years) were evaluated after 55 MBq (0.15 mCi)/kg 18F-FDG utilizing a 16-slice multiple detector CT (MDCT) whole-body PET scanner, with LOR algorithm 3D reconstruction. One- and 2-h imaging was performed in 9 patients. Standard uptake value (SUV) for each lesion, on early and delayed imaging, was calculated. Lesions were confirmed in 6 patients by biopsy. The PET images correlated with MDCT to establish the imaging characteristics. Solitary lesions were found in 4 patients, two lesions in 1 patient, and in 6 patients there were multiple bone lesions. The SUV early ranged from 1.23 to 9.64 with an average of 3.76 ± 2.40. The SUV delayed ranged from 1.76 to 11.42 with an average of 4.51 ± 3.07. The SUV delayed decreased or increased slightly (-31% to 5%) in 6 of our patients, and increased significantly (11% to 39%) in 3. There was a negative correlation between SUVs and age, as well as the number of affected bones. In our study, FDB had wide skeletal distribution with variability of 18F-FDG uptake and CT appearance. SUV in the delayed stage was seen to either decrease or increase on dual-time 18F-FDG PET scanning. It is very important to recognize the characteristics of this skeletal dysplasia to allow differentiation from skeletal metastasis. (orig.)

Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D.

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Nieves, J W

2013-03-01

There is a need to understand the role of nutrition, beyond calcium and vitamin D, in the treatment and prevention of osteoporosis in adults. Results regarding soy compounds on bone density and bone turnover are inconclusive perhaps due to differences in dose and composition or in study population characteristics. The skeletal benefit of black cohosh and red clover are unknown. Dehydroepiandrosterone (DHEA) use may benefit elderly individuals with low serum dehydroepiandrosterone-sulfate levels, but even in this group, there are inconsistent benefits to bone density (BMD). Higher fruit and vegetable intakes may relate to higher BMD. The skeletal benefit of flavonoids, carotenoids, omega-3-fatty acids, and vitamins A, C, E and K are limited to observational data or a few clinical trials, in some cases investigating pharmacologic doses. Given limited data, it would be better to get these nutrients from fruits and vegetables. Potassium bicarbonate may improve calcium homeostasis but with little impact on bone loss. High homocysteine may relate to fracture risk, but the skeletal benefit of each B vitamin is unclear. Magnesium supplementation is likely only required in persons with low magnesium levels. Data are very limited for the role of nutritional levels of boron, strontium, silicon and phosphorus in bone health. A nutrient rich diet with adequate fruits and vegetables will generally meet skeletal needs in healthy individuals. For most healthy adults, supplementation with nutrients other than calcium and vitamin D may not be required, except in those with chronic disease and the frail elderly.

{sup 1}H MR spectroscopy of skeletal muscle, liver and bone marrow

Energy Technology Data Exchange (ETDEWEB)

Machann, Juergen [Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard-Karls University Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany)], E-mail: juergen.machann@med.uni-tuebingen.de; Stefan, Norbert [Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls University Tuebingen, 72076 Tuebingen (Germany); Schick, Fritz [Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard-Karls University Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany)

2008-08-15

Proton magnetic resonance spectroscopy ({sup 1}H MRS) offers interesting metabolic information even from organs outside the brain. In the first part, applications in skeletal muscle for determination of intramyocellular lipids (IMCL), which are involved in the pathogenesis of insulin resistance, are described. Peculiarities of spectral pattern are discussed and studies for short-term regulation of IMCL, as dietary intervention, exercise and fasting are presented. The second part deals with quantification of small amounts of lipids in the liver (hepatic lipids, HL), which is also of increasing interest in the field of diabetes research. Recommendations for correct assessment of spectra in this 'moving organ' are given and the importance of HL is described by examples of a cohort at increased risk for type 2 diabetes. Regulation of HL is described on the basis of a few studies. The third part concentrates on spectral characterization of bone marrow. Peripheral bone marrow of adults consists mainly of fat, while central marrow regions in the pelvis, spinal column and breast bone (and the peripheral bone marrow of children as well) contribute to blood formation and show a variable composition of adipocytes (fat cells), interstitial fluid and water containing precursor cells for erythrocytes, leucocytes and thrombocytes. Adapted {sup 1}H spectroscopic techniques allow a semi-quantitative analysis of bone marrow composition.

Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

Science.gov (United States)

Rianon, N.; McCormick, J.; Ambrose, C.; Smith, S. M.; Fisher-Hoch, S.

2016-01-01

The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (=50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level =8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations

Prevention and Treatment of Bone Metastases in Breast Cancer

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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.

Age-related changes in vertebral and iliac crest 3D bone microstructure-differences and similarities

DEFF Research Database (Denmark)

Thomsen, Jesper Skovhus; Jensen, Michael Vinkel; Niklassen, Andreas Steenholt

2015-01-01

Summary Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure...... was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes.Introduction The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between...... the bone microstructure at these skeletal sites.Methods Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19–96 years) and 39 men (23–95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified.Results For both women...

The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats

Science.gov (United States)

Cavolina, J. M.; Evans, G. L.; Harris, S. A.; Zhang, M.; Westerlind, K. C.; Turner, R. T.

1997-01-01

bone loss in the unloaded limb in excess of that induced by gonadal hormone deficiency. This additional bone loss was arrested by estrogen replacement. We conclude from these studies that estrogen alters the expression of signaling peptides believed to mediate skeletal adaptation to changes in mechanical usage and likewise modifies the skeletal response to mechanical unloading.

Two types of mineral-related matrix vesicles in the bone mineralization of zebrafish

International Nuclear Information System (INIS)

Yang, L; Zhang, Y; Cui, F Z

2007-01-01

Two types of mineral-related matrix vesicle, multivesicular body (MVB) and monovesicle, were detected in the skeletal bone of zebrafish. Transmission electron microscopy and energy dispersive spectroscopy (EDS) analyses of the vesicular inclusions reveal that both types of vesicles contain calcium and phosphorus, suggesting that these vesicles may be involved in mineral ion delivery for the bone mineralization of zebrafish. However, their size and substructure are quite different. Monovesicles, whose diameter ranges from 100 nm to 550 nm, are similar to the previously reported normal matrix vesicles, while MVBs have a larger size of 700-1000 nm in nominal diameter and possess a substructure that is composed of smaller vesicles with their average size around 100 nm. The presence of mineral-related MVBs, which is first identified in zebrafish bone, indicates that the mineralization-associated transportation process of mineral ions is more complicated than is ordinarily imagined

Nutritional factors affecting poultry bone health.

Science.gov (United States)

Fleming, Robert H

2008-05-01

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

Therapy for bone pain palliation in skeletal metastases with Samarium -153 EDTMP (Indonesian experience)

International Nuclear Information System (INIS)

Purnomo, E.

2007-01-01

Full text: Radiopharmaceutical therapy may be used for the treatment of cases with painful skeletal metastases. We evaluate and want to share an experience with application and efficacy of Sm-153 EDTMP in palliative painful bone metastases therapy. Our aim was to determine the efficacy and toxicity of single-dose Sm- 153 EDTMP as a palliative treatment for painful skeletal metastases. Material and methods: we selected 18 patients (9 male, 9 female). The average age 35-65 years weight 40- 60 kg; with metastatic bone confirmed with bone scan examination. 6 with breast cancer, 5 with nasopharyngeal cancer, 5 with prostatic cancer, 2 with lung cancer were treated with 30 mCi ( 1110 MBq) Sm-153 EDTMP. All showed extensive metastatic bone disease. The patients were given intravenous injections of 30 mCi Sm-153 EDTMP, after reconditioning, hydration . We established intensity of pain, haematological parameters, scintigraphic, Karnofsky scale. Clinical assessment was performed one month later. Responses were classified in completed (good response), partial and absent taking into account symptoms and drugs reduction. The discontinuation or the reduction of analgesic drugs like opiate dosage was also considered as successful palliative results of the treatment. Result: pain relief was obtained in 16/18 patients, Sm-153 was effective in patients with reduced drug assumption. The response to Sm-153 was good in 14/18(77,7%) of the patients and partial in 3/18(16,6%) and no response in 1/18(0,5%). The application of Sm-153 in patients with painful disseminated bone metastases has a satisfactory pain alleviating effects. Sides effects were noted, decrease hemoglobin counts and white blood cell and platelets, which gradually returned to near normal after 6 weeks. Easy application and low cost and produced in own country are important factors. Conclusion: radiopharmaceutical therapy can be recommended because of the favorable palliation effect and the low cost of Sm-153, especially

Rescuing loading induced bone formation at senescence.

Directory of Open Access Journals (Sweden)

Sundar Srinivasan

2010-09-01

Full Text Available The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca(2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential.

About 250 cases of skeletal scintiscanning using sup(99m)Tc-labelled stannous pyrophosphate. Analytical and critical study

International Nuclear Information System (INIS)

Suss, Leopold.

1975-01-01

The physical and biological characteristics of 85 Sr, 87 Sr, 18 F and sup(99m)Tc, four radionuclides suitable for skeletal imaging are reviewed. Their mechanism of localization, advantages and disadvantages are described. The physical characteristics and relative tissue concentration of sup(99m)Tc compare favorably to those of the other bone-seeking radionuclides. 250 cases of various skeletal diseases are presented, using sup(99m)Tc-pyrophosphate as a skeletal imaging agent. This radiopharmaceutical proves to be useful particularly in the detection of bone metastases. Bone scans, however, are not 100% positive with metastatic diseases and false negative do occasionally occur. The scan is also helpful in demonstrating the extent of metastatic bone disease [fr

Scintigraphic findings of bone and bone-marrow and determination of bone mineral density using photon absorptiometry in osteopetrosis

International Nuclear Information System (INIS)

Otsuka, Nobuaki; Fukunaga, Masao; Morita, Koichi

1988-01-01

On a 15-year-old girl with osteopetrosis, bone and bonemarrow scintigraphy were performed. Also, bone mineral density (BMD) with quantitative CT (QCT), single photon absorptiometry (SPA) and dual photon absorptiometry (DPA) were measured. On bone scintigraphy the diffusely increased skeletal uptake and relatively diminished renal uptake were noted. On the other hand, on bone marrow scintigraphy poor accumulation in central marrow and peripheral expansion were shown. BMD value by QCT and DPA (mainly trabecular bone) was markedly high, while BMD by SPA (mainly cortical bone) was within normal range. Thus, it was shown that bone and bone-marrow scintigraphy combined with BMD measurement by photon absorptiometry were useful and essential in evaluating the pathophysiology of osteosclerosis. (author)

Correlation between bone mineral density of jaws and skeletal sites in an Iranian population using dual X-ray energy absorptiometry.

Science.gov (United States)

Esfahanizadeh, Nasrin; Davaie, Sotoudeh; Rokn, A R; Daneshparvar, Hamid Reza; Bayat, Noushin; Khondi, Nasrin; Ajvadi, Sara; Ghandi, Mostafa

2013-07-01

The aim of the present study was to evaluate the relationship between the bone density of various regions of jaws and skeletal bones. A total of 110 patients with a mean age of 55.01 ± 10.77 years were selected for the purpose of the present descriptive study. Dual X-ray Energy Absorptiometry (DXA) was carried out to determine bone mineral density (BMD) of the femur and lumbar vertebrae. Then all the subjects underwent DXA of the jaw bones and BMD values were determined at four jaw regions. Data were analyzed by SPSS 16 statistical software, and the correlation between the various BMD values was determined by Pearson's correlation coefficient. The results showed that 42.7% of females had normal BMD values in the femur, and in vertebrae, 20% were osteopenic and 37.3% suffered from osteoporosis, with statistically significant differences in the BMD values of the jaws between the three above-mentioned groups (P < 0.001). There was an increasing tendency toward osteopenia and osteoporosis with age. There was a positive correlation between BMD values of the femur and lumbar vertebrae and those of all the jaw regions under study (P < 0.005). There was a negative correlation (P < 0.01) between age and the BMD values of the femur, lumbar vertebrae and anterior maxilla. The bone density of the maxilla and mandible and presence of osteoporosis or osteopenia in these bones might reflect the same problem in skeletal bones.

Comparison of diffusion-weighted whole body MRI and skeletal scintigraphy for the detection of bone metastases in patients with prostate or breast carcinoma

International Nuclear Information System (INIS)

Gutzeit, Andreas; Doert, Aleksis; Froehlich, Johannes M.; Eckhardt, Boris P.; Meili, Andreas; Scherr, Patrick; Schmid, Daniel T.; Weymarn, Constantin A. von; Willemse, Edwin M.M.; Binkert, Christoph A.; Graf, Nicole

2010-01-01

To prospectively compare the diagnostic accuracy of diffusion-weighted whole body imaging with background whole body signal suppression (DWIBS) with skeletal scintigraphy for the diagnosis and differentiation of skeletal lesions in patients suffering from prostate or breast cancer. A diagnostic cohort of 36 patients was included in skeletal scintigraphy and 1.5 T DWIBS MRI. Based on morphology and signal intensity patterns, two readers each identified and classified independently, under blinded conditions, all lesions into three groups: (1) malignant, (2) unclear if malignant or benign and (3) benign. Finally, for the definition of the gold standard all available imaging techniques and follow-up over a minimum of 6 months were considered. Overall, 45 circumscribed bone metastases and 107 benign lesions were found. DWIBS performed significantly better in detecting malignant skeletal lesions in patients with more than 10 lesions (sensitivity: 0.97/0.91) compared to skeletal scintigraphy (sensitivity: 0.48/0.42). No statistical difference could be found between DWIBS (0.58/0.33) and skeletal scintigraphy (0.67/0.58) in the sensitivity values for malignant skeletal lesions in patients with less than 5 lesions. For benign lesions, scintigraphy scored best with a sensitivity of 0.93/0.87 compared to 0.20/0.13 for DWIBS. Interobserver agreement with Cohen's kappa coefficient was calculated as 0.784 in the case of scintigraphy and 0.663 for DWIBS. With respect to staging, in prostate and breast carcinoma, the DWIBS technique is not superior to skeletal scintigraphy, but ranks equally. However, in the cases with many bone lesions, markedly more metastases could be discovered using the DWIBS technique than skeletal scintigraphy. (orig.)

The skeletal consequences of thyrotoxicosis.

Science.gov (United States)

Nicholls, Jonathan J; Brassill, Mary Jane; Williams, Graham R; Bassett, J H Duncan

2012-06-01

Euthyroid status is essential for normal skeletal development and the maintenance of adult bone structure and strength. Established thyrotoxicosis has long been recognised as a cause of high bone turnover osteoporosis and fracture but more recent studies have suggested that subclinical hyperthyroidism and long-term suppressive doses of thyroxine (T4) may also result in decreased bone mineral density (BMD) and an increased risk of fragility fracture, particularly in postmenopausal women. Furthermore, large population studies of euthyroid individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set point at the upper end of the normal reference range is associated with reduced BMD and increased fracture susceptibility. Despite these findings, the cellular and molecular mechanisms of thyroid hormone action in bone remain controversial and incompletely understood. In this review, we discuss the role of thyroid hormones in bone and the skeletal consequences of hyperthyroidism.

Radiological diagnosis of skeletal metastases

International Nuclear Information System (INIS)

Soederlund, V.

1996-01-01

The clinical management of patients with skeletal metastases puts new demands on imaging. The radiological imaging in screening for skeletal metastases entails detection, metastatic site description and radiologically guided biopsy for morphological typing and diagnosis. Regarding sensitivity and the ease in performing surveys of the whole skeleton, radionuclide bone scintigraphy still is the first choice in routine follow-up of asymptomatic patients with metastatic disease of the skeleton. A negative scan has to be re-evaluated with other findings, with emphasis on the possibility of a false-negative result. Screening for metastases in patients with local symptoms or pain is best accomplished by a combination of radiography and MRI. Water-weighted sequences are superior in sensitivity and in detection of metastases. Standard spin-echo sequences on the other hand are superior in metastatic site description and in detection of intraspinal metastases. MRI is helpful in differentiating between malignant disease, infection, benign vertebral collapse, insufficiency fracture after radiation therapy, degenerative vertebral disease and benign skeletal lesions. About 30% of patients with known cancer have benign causes of radiographic abnormalities. Most of these are related to degenerative diseases and are often easily diagnosed. However, due to overlap in MRI characteristics, bone biopsy sometimes is essential for differentiating between malignant and nonmalignant lesions. Performing bone biopsy and aspiration cytology by radiologist and cytologist in co-operation has proven highly accurate in diagnosing bone lesions. The procedure involves low risk to the patient and provides a morphological diagnosis. Once a suspected metastatic lesion is detected, irrespective of modality, the morphological diagnosis determines the appropriate work-up imaging with respect to the therapy alternatives. (orig./VHE)

Bone Disease in Axial Spondyloarthritis.

Science.gov (United States)

Van Mechelen, Margot; Gulino, Giulia Rossana; de Vlam, Kurt; Lories, Rik

2018-05-01

Axial spondyloarthritis is a chronic inflammatory skeletal disorder with an important burden of disease, affecting the spine and sacroiliac joints and typically presenting in young adults. Ankylosing spondylitis, diagnosed by the presence of structural changes to the skeleton, is the prototype of this disease group. Bone disease in axial spondyloarthritis is a complex phenomenon with the coexistence of bone loss and new bone formation, both contributing to the morbidity of the disease, in addition to pain caused by inflammation. The skeletal structural changes respectively lead to increased fracture risk and to permanent disability caused by ankylosis of the sacroiliac joints and the spine. The mechanism of this new bone formation leading to ankylosis is insufficiently known. The process appears to originate from entheses, specialized structures that provide a transition zone in which tendon and ligaments insert into the underlying bone. Growth factor signaling pathways such as bone morphogenetic proteins, Wnts, and Hedgehogs have been identified as molecular drivers of new bone formation, but the relationship between inflammation and activation of these pathways remains debated. Long-standing control of inflammation appears necessary to avoid ankylosis. Recent evidence and concepts suggest an important role for biomechanical factors in both the onset and progression of the disease. With regard to new bone formation, these processes can be understood as ectopic repair responses secondary to inflammation-induced bone loss and instability. In this review, we discuss the clinical implications of the skeletal changes as well as the underlying molecular mechanisms, the relation between inflammation and new bone formation, and the potential role of biomechanical stress.

Multiscale characterization of the mineral phase at skeletal sites of breast cancer metastasis

Science.gov (United States)

Chiou, Aaron E.; Loh, Hyun Chae; Lynch, Maureen; Seo, Bo Ri; Song, Young Hye; Hoerth, Rebecca; Bortel, Emely L.; Willie, Bettina M.; Duda, Georg N.; Masic, Admir; Wagermaier, Wolfgang; Fratzl, Peter; Fischbach, Claudia

2017-01-01

Skeletal metastases, the leading cause of death in advanced breast cancer patients, depend on tumor cell interactions with the mineralized bone extracellular matrix. Bone mineral is largely composed of hydroxyapatite (HA) nanocrystals with physicochemical properties that vary significantly by anatomical location, age, and pathology. However, it remains unclear whether bone regions typically targeted by metastatic breast cancer feature distinct HA materials properties. Here we combined high-resolution X-ray scattering analysis with large-area Raman imaging, backscattered electron microscopy, histopathology, and microcomputed tomography to characterize HA in mouse models of advanced breast cancer in relevant skeletal locations. The proximal tibial metaphysis served as a common metastatic site in our studies; we identified that in disease-free bones this skeletal region contained smaller and less-oriented HA nanocrystals relative to ones that constitute the diaphysis. We further observed that osteolytic bone metastasis led to a decrease in HA nanocrystal size and perfection in remnant metaphyseal trabecular bone. Interestingly, in a model of localized breast cancer, metaphyseal HA nanocrystals were also smaller and less perfect than in corresponding bone in disease-free controls. Collectively, these results suggest that skeletal sites prone to tumor cell dissemination contain less-mature HA (i.e., smaller, less-perfect, and less-oriented crystals) and that primary tumors can further increase HA immaturity even before secondary tumor formation, mimicking alterations present during tibial metastasis. Engineered tumor models recapitulating these spatiotemporal dynamics will permit assessing the functional relevance of the detected changes to the progression and treatment of breast cancer bone metastasis. PMID:28923958

Radiopharmaceuticals for bone scintillators

International Nuclear Information System (INIS)

Rey, A.M.

1994-01-01

One of the diagnostic techniques used in nuclear medicine is the bone scintiscanning with labelled compounds for obtain skeletal images. The main sections in this work are: (1) bone composition and anatomy;(2)skeletal radiopharmaceutical development;(3)physical properties of radionuclides;(4)biological behaviour and chemical structures;(5)radiopharmaceuticals production for skeletal scintillation;(6)kits;(7)dosimetry and toxicity.tabs

Mus musculus bone fluoride concentration as a useful biomarker for risk assessment of skeletal fluorosis in volcanic areas.

Science.gov (United States)

Linhares, Diana; Camarinho, Ricardo; Garcia, Patrícia Ventura; Rodrigues, Armindo Dos Santos

2018-08-01

Fluoride is often found in elevated concentrations in volcanic areas due to the release of magmatic fluorine as hydrogen fluorine through volcanic degassing. The exposure to high levels of fluoride can affect the processes of bone formation and resorption causing skeletal fluorosis, a pathology that can easily be mistaken for other skeletal diseases. In this study, we aimed to determine if fluoride concentration in the femoral bone of wild populations of the house mouse (Mus musculus) is a good biomarker of exposure to active volcanic environments naturally enriched in fluoride, allowing their use in biomonitoring programs. The fluoride concentration of the whole femoral bone of 9 mice from Furnas (5 males and 4 females) and 33 mice from Rabo de Peixe (16 males and 17 females) was measured by the potentiometric method with a fluoride ion selective electrode. Fluoride in bones was significantly higher in the mice from Furnas when compared with the mice from Rabo de Peixe (616.5 ± 129.3 μg F/g vs. 253.8 ± 10.5 μg F/g). Accumulation rates were also significantly higher in the mice collected in Furnas when compared with Rabo de Peixe individuals (3.84 ± 0.52 μg F/day vs. 1.22 ± 0.06 μg F/day). The results demonstrate a significant association between exposure to fluoride in the active volcanic environment and fluoride content in bone, revealing that bone fluoride concentration is a suitable biomarker of chronic environmental exposure to fluoride. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gene expression patterns related to osteogenic differentiation of bone marrow-derived mesenchymal stem cells during ex vivo expansion.

Science.gov (United States)

Granchi, Donatella; Ochoa, Gorka; Leonardi, Elisa; Devescovi, Valentina; Baglìo, Serena Rubina; Osaba, Lourdes; Baldini, Nicola; Ciapetti, Gabriela

2010-06-01

Bone marrow is commonly used as a source of adult multipotent mesenchymal stem cells (MSCs), defined for their ability to differentiate in vitro into multiple lineages. The ex vivo-expanded MSCs are currently being evaluated as a strategy for the restoration of function in damaged skeletal tissue, both in cell therapy and tissue engineering applications. The aim of this study was to define gene expression patterns underlying the differentiation of MSCs into mature osteoblasts during the expansion in vitro, and to explore a variety of cell functions that cannot be easily evaluated using morphological, cytochemical, and biochemical assays. Cell cultures were obtained from bone marrow samples of six individuals undergoing total hip replacement, and a large-scale transcriptome analysis, using Affymetrix HG-U133A Plus 2.0 array (Affymetrix((R)), Santa Clara, CA), was performed at the occurrence of specific events, including the appearance of MSC surface markers, formation of colonies, and deposition of mineral nodules. We focused our attention on 213 differentially upregulated genes, some belonging to well-known pathways and some having one or more Gene Ontology annotations related to bone cell biology, including angiogenesis, bone-related genes, cell communication, development and morphogenesis, transforming growth factor-beta signaling, and Wnt signaling. Twenty-nine genes, whose role in bone cell pathophysiology has not been described yet, were found. In conclusion, gene expression patterns that characterize the early, intermediate, and late phases of the osteogenic differentiation process of ex vivo-expanded MSCs were defined. These signatures represent a useful tool to monitor the osteogenic process, and to analyze a broad spectrum of functions of MSCs cultured on scaffolds, especially when the constructs are conceived for releasing growth factors or other signals to promote bone regeneration.

Oncological outcomes of patients with Ewing's sarcoma: is there a difference between skeletal and extra-skeletal Ewing's sarcoma?

Science.gov (United States)

Pradhan, A; Grimer, R J; Spooner, D; Peake, D; Carter, S R; Tillman, R M; Abudu, A; Jeys, L

2011-04-01

The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing's sarcoma. We identified 300 patients with new primary Ewing's sarcoma diagnosed between 1980 and 2005 from the centres' local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing's sarcomas. Although patients with skeletal Ewing's were younger (mean age 16.8 years) than those with extra-skeletal Ewing's sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing's sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not. This large series has shown that the oncological outcomes of Ewing's sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue.

Correlation between bone mineral density of jaws and skeletal sites in an Iranian population using dual X-ray energy absorptiometry

Directory of Open Access Journals (Sweden)

Nasrin Esfahanizadeh

2013-01-01

Full Text Available Background: The aim of the present study was to evaluate the relationship between the bone density of various regions of jaws and skeletal bones. Materials and Methods: A total of 110 patients with a mean age of 55.01 ± 10.77 years were selected for the purpose of the present descriptive study. Dual X-ray Energy Absorptiometry (DXA was carried out to determine bone mineral density (BMD of the femur and lumbar vertebrae. Then all the subjects underwent DXA of the jaw bones and BMD values were determined at four jaw regions. Data were analyzed by SPSS 16 statistical software, and the correlation between the various BMD values was determined by Pearson′s correlation coefficient. Results: The results showed that 42.7% of females had normal BMD values in the femur, and in vertebrae, 20% were osteopenic and 37.3% suffered from osteoporosis, with statistically significant differences in the BMD values of the jaws between the three above-mentioned groups (P < 0.001. There was an increasing tendency toward osteopenia and osteoporosis with age. There was a positive correlation between BMD values of the femur and lumbar vertebrae and those of all the jaw regions under study (P < 0.005. There was a negative correlation (P < 0.01 between age and the BMD values of the femur, lumbar vertebrae and anterior maxilla. Conclusion: The bone density of the maxilla and mandible and presence of osteoporosis or osteopenia in these bones might reflect the same problem in skeletal bones.

Skeletal and reticuloendothelial imaging in osteopetrosis: case report

International Nuclear Information System (INIS)

Park, H.M.; Lambertus, J.

1977-01-01

Skeletal and reticuloendothelial images, using Tc-99m HEDP and Tc-99m sulfur colloid, respectively, were obtained from two adult patients with osteopetrosis. Skeletal images demonstrated increased activity in multiple fracture sites, in mandibular osteomyelitis, in ends of splayed long bones adjacent to joints, and in the epiphyseal ends of short tubular bones. The remainder of the skeleton involved with osteopetrosis showed no generalized increased uptake of Tc-99m HEDP. These findings indicate that metabolic activity in this disease is abnormally increased in the usual areas of bone growth but appears normal elsewhere. Reticuloendothelial imaging showed an almost total lack of activity in the axial and peripheral skeletal marrow space. Anemia, however, was only moderate in these patients. Skeletal scintigraphy may be useful to evaluate the presence and extent of the frequent complications of osteopetrosis, namely fractures and osteomyelitis

Long-term skeletal findings in Menkes disease

International Nuclear Information System (INIS)

Amador, Eva; Domene, Ruth; Fuentes, Cristian; Carreno, Juan-Carlos; Enriquez, Goya

2010-01-01

Skeletal findings in infants with Menkes disease, the most characteristic of which are metaphyseal spurs, long-bone fractures and wormian bones, have been widely reported. However, the changes in skeletal features over time are not well known. The long-term findings differ completely from those initially observed and consist of undertubulation and metaphyseal flaring, similar to the findings seen in some types of bone dysplasia. The initial and long-term radiological features in an 8-year-old boy with Menkes disease are illustrated. (orig.)

Expression of Gla proteins during fish skeletal development

OpenAIRE

Gavaia, Paulo J.

2006-01-01

Senegal sole skeletal development; Skeletal malformations; Skeletal malformation in mediterranean species; Senegal sole skeletal deformities; Zebra fish as model system: skeletal development; Identification of bone cells / skeletal development; Spatial - temporal pattern of bgp expression; Single cell resolution: localization of bgp mRNA; Single cell resolution: Immunolocalization of Bgp; Single cell resolution: localization of mgp mRNA; Single cell resolution: Immunolocalization of Mgp; An i...

Unicameral Bone Cyst of the Medial Cuneiform.

Science.gov (United States)

Schick, Faith A; Daniel, Joseph N; Miller, Juliane S

2016-09-02

A unicameral bone cyst is a relatively uncommon, benign bone tumor found in the metaphysis of long bones, such as the humerus and the femur, in skeletally immature persons. In the foot, these benign, fluid-filled cavities are most commonly found within the os calcis. We present a case report of a 10-year-old female with a unicameral bone cyst of the medial cuneiform.

Transgenic Mouse Model for Reducing Oxidative Damage in Bone

Science.gov (United States)

Schreurs, Ann-Sofie; Torres, S.; Truong, T.; Moyer, E. L.; Kumar, A.; Tahimic, Candice C. G.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

2016-01-01

Bone loss can occur due to many challenges such age, radiation, microgravity, and Reactive Oxygen Species (ROS) play a critical role in bone resorption by osteoclasts (Bartell et al. 2014). We hypothesize that suppression of excess ROS in skeletal cells, both osteoblasts and osteoclasts, regulates skeletal growth and remodeling. To test our hypothesis, we used transgenic mCAT mice which overexpress the human anti-oxidant catalase gene targeted to the mitochondria, the main site for endogenous ROS production. mCAT mice have a longer life-span than wildtype controls and have been used to study various age-related disorders. To stimulate remodeling, 16 week old mCAT mice or wildtype mice were exposed to treatment (hindlimb-unloading and total body-irradiation) or sham treatment conditions (control). Tissues were harvested 2 weeks later for skeletal analysis (microcomputed tomography), biochemical analysis (gene expression and oxidative damage measurements), and ex vivo bone marrow derived cell culture (osteoblastogenesis and osteoclastogenesis). mCAT mice expressed the transgene and displayed elevated catalase activity in skeletal tissue and marrow-derived osteoblasts and osteoclasts grown ex vivo. In addition, when challenged with treatment, bone tissues from wildtype mice showed elevated levels of malondialdehyde (MDA), indicating oxidative damage) whereas mCAT mice did not. Correlation analysis revealed that increased catalase activity significantly correlated with decreased MDA levels and that increased oxidative damage correlated with decreased percent bone volume (BVTV). In addition, ex-vivo cultured osteoblast colony growth correlated with catalase activity in the osteoblasts. Thus, we showed that these transgenic mice can be used as a model to study the relationship between markers of oxidative damage and skeletal properties. mCAT mice displayed reduced BVTV and trabecular number relative to wildtype mice, as well as increased structural model index in the

How the mach phenomenon and shape affect the radiographic appearance of skeletal structures

International Nuclear Information System (INIS)

Papageorges, M.

1991-01-01

The shape of skeletal structures and their position relative to the x-ray beam have a considerable effect on their radiographic appearance. Depending on the thickness of the cortical or subchondral bone, skeletal structures display the characteristics of either homogeneous or compound lamellar structures. Convex homogeneous structures are associated with a negative Mach line, and concave homogeneous structures are associated with a positive Mach line. Convex compound lamellar structures are associated with a negative Mach band and visualization of the lamina (subchondral or cortical bone) is reduced. Concave compound lamellar structures are associated with a positive Mach band and visualization of the lamina is enhanced. The combined effect of Mach phenomenon, shape, and thickness enhances visualization of some skeletal surfaces and make others imperceptible. These principles are very useful to correctly identify complex skeletal structures and avoid misinterpretations

Bisphosphonate-related osteonecrosis of the jaw: historical, ethical, and legal issues associated with prescribing.

Science.gov (United States)

Faiman, Beth; Pillai, Aiswarya Lekshmi Pillai Chandran; Benghiac, Ana Gabriela

2013-01-01

The long-term effects of many drugs are unknown. Established risks are communicated to patients who participate in clinical trials during the informed consent process. However, unknown and unanticipated side effects of medications may occur years after treatment. Patients with metastatic bone cancer experience an imbalance between tumor cells and the bone marrow microenvironment. Increased cytokine release, osteoclastic activity, and uncoupled osteoblastic activity lead to weakened bone structure and osteolytic lesions. The bisphosphonates are a class of drugs available in IV and oral formulations to treat and prevent bone loss and decrease the risk of skeletal-related events. Intravenous bisphosphonates such as zoledronic acid and pamidronate disodium are approved by the US Food and Drug Administration for the treatment of bone pain and hypercalcemia of malignancy and the prevention of painful bone fractures in patients with metastatic bone cancer. Oral bisphosphonates such as alendronate, risedronate, and etidronate are used to reduce the risk of skeletal fractures in patients with osteoporosis and in breast cancer. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but painful complication of treatment characterized by infection, exposed bone, and poor wound healing. In this article, we discuss BRONJ and identify past, present, and future ethical and legal issues surrounding bisphosphonate administration.

Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events

DEFF Research Database (Denmark)

Acquavella, John; Ehrenstein, Vera; Schiødt, Morten

2016-01-01

OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authoriza......OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post...... (120 mg subcutaneously) or zoledronic acid (4 mg intravenously, adjusted for renal function). Patients will be identified using routinely collected data combined with medical chart review in Denmark, Sweden, and Norway. Followup will extend from the first administration of antiresorptive treatment...... to the earliest of death, loss-to-follow-up, or 5 years after therapy initiation. Results will be reported for three treatment cohorts: denosumab-naïve patients, zoledronic acid-naïve patients, and patients who switch from bisphosphonate treatment to denosumab. ONJ cases will be identified in three newly...

Skeletal blood flow, iliac histomorphometry, and strontium kinetics in osteoporosis: a relationship between blood flow and corrected apposition rate

International Nuclear Information System (INIS)

Reeve, J.; Arlot, M.; Wootton, R.; Edouard, C.; Tellez, M.; Hesp, R.; Green, J.R.; Meunier, P.J.

1988-01-01

In 20 untreated patients with idiopathic or postmenopausal osteoporosis, kinetic studies of skeletal blood flow (using 18 F) and bone turnover (using 85 Sr) were combined with dynamic histomorphometry performed on transiliac biopsies taken within 6 weeks of each other. In 8 patients the combined studies were repeated after treatment. A further 5 patients were studied only while receiving treatment. As expected, skeletal blood flow measured by 18 F correlated with an index of 85 Sr uptake into the exchangeable pools of bone. Additionally and independently, skeletal blood flow correlated with an index of the work rate of the osteoblasts in each multicellular unit of bone (the corrected apposition rate of Parfitt). These correlations were statistically significant in both the untreated patients (P less than 0.05) and the whole group (P less than 0.001). Further indices related to bone turnover at the level of the skeleton as a whole were significantly associated with skeletal blood flow only in the combined group

An image-based skeletal tissue model for the ICRP reference newborn

Energy Technology Data Exchange (ETDEWEB)

Pafundi, Deanna; Lee, Choonsik; Bolch, Wesley [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, FL (United States); Watchman, Christopher; Bourke, Vincent [Department of Radiation Oncology, University of Arizona, Tucson, AZ (United States); Aris, John [Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (United States); Shagina, Natalia [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation); Harrison, John; Fell, Tim [Radiation Protection Division, Health Protection Agency, Chilton (United Kingdom)], E-mail: wbolch@ufl.edu

2009-07-21

Hybrid phantoms represent a third generation of computational models of human anatomy needed for dose assessment in both external and internal radiation exposures. Recently, we presented the first whole-body hybrid phantom of the ICRP reference newborn with a skeleton constructed from both non-uniform rational B-spline and polygon-mesh surfaces (Lee et al 2007 Phys. Med. Biol. 52 3309-33). The skeleton in that model included regions of cartilage and fibrous connective tissue, with the remainder given as a homogenous mixture of cortical and trabecular bone, active marrow and miscellaneous skeletal tissues. In the present study, we present a comprehensive skeletal tissue model of the ICRP reference newborn to permit a heterogeneous representation of the skeleton in that hybrid phantom set-both male and female-that explicitly includes a delineation of cortical bone so that marrow shielding effects are correctly modeled for low-energy photons incident upon the newborn skeleton. Data sources for the tissue model were threefold. First, skeletal site-dependent volumes of homogeneous bone were obtained from whole-cadaver CT image analyses. Second, selected newborn bone specimens were acquired at autopsy and subjected to micro-CT image analysis to derive model parameters of the marrow cavity and bone trabecular 3D microarchitecture. Third, data given in ICRP Publications 70 and 89 were selected to match reference values on total skeletal tissue mass. Active marrow distributions were found to be in reasonable agreement with those given previously by the ICRP. However, significant differences were seen in total skeletal and site-specific masses of trabecular and cortical bone between the current and ICRP newborn skeletal tissue models. The latter utilizes an age-independent ratio of 80%/20% cortical and trabecular bone for the reference newborn. In the current study, a ratio closer to 40%/60% is used based upon newborn CT and micro-CT skeletal image analyses. These changes in

Current role of bone scan with phosphonates in the follow-up of breast cancer

International Nuclear Information System (INIS)

Maffioli, Lorenzo; Florimonte, Luigia; Pagani, Luca; Butti, Ivana; Roca, Isabel

2004-01-01

A number of studies have demonstrated that bone scintigraphy has high sensitivity and efficacy in the early detection of bone metastases from several tumours, including breast cancer. Bone scintigraphy is the most definitive tool for diagnosing and monitoring metastatic spread of breast cancer. However, in the past decade there has been a wide debate on its impact on survival time, morbidity and quality of life. Worldwide economic restrictions and these studies have led to the adoption of an almost minimalist policy for breast cancer follow-up using evidence-based guidelines. The recommended breast cancer surveillance testing includes only a few procedures (history, physical and breast self-examination, patient education on symptoms, pelvic examination). The routine use of additional tests, such as blood cell count, tumour markers, liver ultrasonography, bone scan and chest X-rays, is not recommended. Accordingly, scintigraphy should be reserved for a limited number of patients. On the other hand, early diagnosis of bone involvement may reduce the risk of skeletal related events, thus leading to a significant improvement in quality of life. Furthermore, new drugs (e.g. bisphosphonates) can now delay the onset of bone metastasis and reduce the number of patients who experience skeletal complications. In conclusion, the evidence of the clinical usefulness of bone scintigraphy (to allow early planning of new treatments in advanced disease) has to be re-evaluated, possibly by large randomised prospective trials. (orig.)

Skeletal muscle contraction in protecting joints and bones by absorbing mechanical impacts

Science.gov (United States)

Rudenko, O. V.; Tsyuryupa, S.; Sarvazyan, A.

2016-09-01

We have previously hypothesized that the dissipation of mechanical energy of external impact is a fundamental function of skeletal muscle in addition to its primary function to convert chemical energy into mechanical energy. In this paper, a mathematical justification of this hypothesis is presented. First, a simple mechanical model, in which the muscle is considered as a simple Hookean spring, is considered. This analysis serves as an introduction to the consideration of a biomechanical model taking into account the molecular mechanism of muscle contraction, kinetics of myosin bridges, sarcomere dynamics, and tension of muscle fibers. It is shown that a muscle behaves like a nonlinear and adaptive spring tempering the force of impact and increasing the duration of the collision. The temporal profiles of muscle reaction to the impact as functions of the levels of muscle contraction, durations of the impact front, and the time constants of myosin bridges closing, are obtained. The absorption of mechanical shock energy is achieved due to the increased viscoelasticity of the contracting skeletal muscle. Controlling the contraction level allows for the optimization of the stiffness and viscosity of the muscle necessary for the protection of the joints and bones.

Findings of skin and bones in mastocytosis

International Nuclear Information System (INIS)

Rohner, H.G.; Bartl, R.; Koischwitz, D.; Rodermund, O.E.

1982-01-01

The syndrome of mastocytosis can include isolated urticaria pigmentosa, systemic mastocytosis, or the extremely rare form of mast cell leucemia. Our investigations of many patients have shown more frequently than earlier suspected, that the mastocytosis is a systemic disease. The frequency of attacked bone marrow is noteworthy. Because of the inflammatorygranulomatous manifestation in bone marrow, considerations of the pathogenesis of an immune and reactive event are taken into account. The mast cell granulomas are mostly found in the endosteal region, which is the reason for frequenctly occurring bone lesions (half on all patients show bone lesions). The bone changes can develop generalized (osteoporosis-osteosclerosis) or localized (osteolytic-osteosclerotic foci). In clinical work bone biopsies and skeletal radiology are supplementing each other: bone biopsy and skin biopsy give the first diagnosis of mastocytosis and reveal the systemic disease; X-ray pictures give information of shape and dimension of the induced osteopathy. (orig.)

Findings of skin and bones in mastocytosis

Energy Technology Data Exchange (ETDEWEB)

Rohner, H.G.; Bartl, R.; Koischwitz, D.; Rodermund, O.E.

1982-12-01

The syndrome of mastocytosis can include isolated urticaria pigmentosa, systemic mastocytosis, or the extremely rare form of mast cell leucemia. Our investigations of many patients have shown more frequently than earlier suspected, that the mastocytosis is a systemic disease. The frequency of attacked bone marrow is noteworthy. Because of the inflammatory granulomatous manifestation in bone marrow, considerations of the pathogenesis of an immune and reactive event are taken into account. The mast cell granulomas are mostly found in the endosteal region, which is the reason for frequently occurring bone lesions (half of all patients show bone lesions). The bone changes can develop generalized (osteoporosis-osteosclerosis) or localized (osteolytic-osteosclerotic foci). In clinical work bone biopsies and skeletal radiology are supplementing each other: bone biopsy and skin biopsy give the first diagnosis of mastocytosis and reveal the systemic disease; X-ray pictures give information of shape and dimension of the induced osteopathy.

Samarium-153 EDTMP therapy of disseminated skeletal metastasis

International Nuclear Information System (INIS)

Turner, J.H.; Martindale, A.A.; Fleay, R.F.; Hoffman, R.F.; Claringbold, P.G.

1989-01-01

153 Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153 Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153 Sm-EDTMP in 15 of 19 patients (79%) who could vie evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153 Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow ≥270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153 Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153 Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 0.5% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153 Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153 Sm-EDTMP-induced myelotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients. (orig.)

Camouflage treatment of skeletal class III malocclusion with asymmetry using a bone-borne rapid maxillary expander.

Science.gov (United States)

Seo, Yu-Jin; Chung, Kyu-Rhim; Kim, Seong-Hun; Nelson, Gerald

2015-03-01

This case report presents the successful use of palatal mini-implants for rapid maxillary expansion and mandibular distalization in a skeletal Class III malocclusion. The patient was a 13-year-old girl with the chief complaint of facial asymmetry and a protruded chin. Camouflage orthodontic treatment was chosen, acknowledging the possibility of need for orthognathic surgery after completion of her growth. A bone-borne rapid expander (BBRME) was used to correct the transverse discrepancy and was then used as indirect anchorage for distalization of the lower dentition with Class III elastics. As a result, a Class I occlusion with favorable inclination of the upper teeth was achieved without any adverse effects. The total treatment period was 25 months. Therefore, BBRME can be considered an alternative treatment in skeletal Class III malocclusion.

The role of vasculature in bone development, regeneration and proper systemic functioning.

Science.gov (United States)

Filipowska, Joanna; Tomaszewski, Krzysztof A; Niedźwiedzki, Łukasz; Walocha, Jerzy A; Niedźwiedzki, Tadeusz

2017-08-01

Bone is a richly vascularized connective tissue. As the main source of oxygen, nutrients, hormones, neurotransmitters and growth factors delivered to the bone cells, vasculature is indispensable for appropriate bone development, regeneration and remodeling. Bone vasculature also orchestrates the process of hematopoiesis. Blood supply to the skeletal system is provided by the networks of arteries and arterioles, having distinct molecular characteristics and localizations within the bone structures. Blood vessels of the bone develop through the process of angiogenesis, taking place through different, bone-specific mechanisms. Impaired functioning of the bone blood vessels may be associated with the occurrence of some skeletal and systemic diseases, i.e., osteonecrosis, osteoporosis, atherosclerosis or diabetes mellitus. When a disease or trauma-related large bone defects appear, bone grafting or bone tissue engineering-based strategies are required. However, a successful bone regeneration in both approaches largely depends on a proper blood supply. In this paper, we review the most recent data on the functions, molecular characteristics and significance of the bone blood vessels, with a particular emphasis on the role of angiogenesis and blood vessel functioning in bone development and regeneration, as well as the consequences of its impairment in the course of different skeletal and systemic diseases.

Evaluation of bone-seeking novel radiotracer {sup 68}Ga-NO2AP-Bisphosphonate for the detection of skeletal metastases in carcinoma breast

Energy Technology Data Exchange (ETDEWEB)

Passah, Averilicia; Tripathi, Madhavi; Ballal, Sanjana; Yadav, Madhav Prasad; Kumar, Rajeev; Chakraborty, Partha Sarathi; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Roesch, Frank; Meckel, Marian [Johannes-Gutenberg-University, Nuclear Chemistry, Mainz (Germany)

2017-01-15

The successful labelling of bisphosphonates (BP) with {sup 68}Ga using macrocyclic chelators such as the based triazacyclononane (NO2AP) is a step forward in the in-house availability of a novel bone-seeking PET radiopharmaceutical with dual advantage of PET/CT imaging and generator production. In this study, we compared the novel generator-based skeletal radiotracer {sup 68}Ga-1,4,7-triazacyclonone-1,4-diacetic acid ({sup 68}Ga-NO2AP-BP) with sodium fluoride ({sup 18}F-NaF) for the detection of skeletal metastases in breast cancer patients. In addition, dosimetric analysis of {sup 68}Ga-NO2AP-BP was performed in a subset of patients. This was a prospective study of histopathologically proven cases of breast cancer patients who were referred for bone scintigraphy and underwent positron emission tomography/computed tomography (PET/CT) with {sup 18}F-NaF and {sup 68}Ga-NO2AP-BP within a week in random order. The scans of each patient were compared both qualitatively for image quality and quantitatively for number of lesions and SUVmax of lesions. Dosimetric analysis was performed in five patients. Their PET/CT scans were acquired at multiple time points and urine and blood samples were collected. Dosimetric calculations were performed using OLINDA/EXM 1.1 software. Statistical analysis was done using Stata 13 (StataCorp) software package. An agreement analysis regarding number of lesions detected with the two skeletal radiotracers was carried out. The image quality of {sup 68}Ga-NO2AP-BP PET/CT scans were comparable to that of {sup 18}F-NaF. There was no statistically significant difference in the SUVmax of lesions, normal bone and lesion to background ratio between the two skeletal radiotracers. There was good agreement in the number of lesions detected by both skeletal radiotracers. The mean whole body effective dose for {sup 68}Ga-NO2AP-BP was 0.00583 mSv/MBq and the effective dose equivalent was 0.0086 mSv/MBq. The excellent lesion detection agreement between

Unique biochemical and mineral composition of whale ear bones.

Science.gov (United States)

Kim, Sora L; Thewissen, J G M; Churchill, Morgan M; Suydam, Robert S; Ketten, Darlene R; Clementz, Mark T

2014-01-01

Abstract Cetaceans are obligate aquatic mammals derived from terrestrial artiodactyls. The defining characteristic of cetaceans is a thick and dense lip (pachyosteosclerotic involucrum) of an ear bone (the tympanic). This unique feature is absent in modern terrestrial artiodactyls and is suggested to be important in underwater hearing. Here, we investigate the mineralogical and biochemical properties of the involucrum, as these may hold clues to the aquatic adaptations of cetaceans. We compared bioapatites (enamel, dentine, cementum, and skeletal bone) of cetaceans with those of terrestrial artiodactyls and pachyosteosclerotic ribs of manatees (Sirenia). We investigated organic, carbonate, and mineral composition as well as crystal size and crystallinity index. In all studied variables, bioapatites of the cetacean involucrum were intermediate in composition and structure between those of tooth enamel on the one hand and those of dentine, cementum, and skeletal bone on the other. We also studied the amino acid composition of the cetacean involucrum relative to that of other skeletal bone. The central involucrum had low glycine and hydroxyproline concentrations but high concentrations of nonessential amino acids, unlike most bone samples but similar to the tympanic of hippos and the (pachyosteosclerotic) ribs of manatees. These amino acid results are evidence of rapid bone development. We hypothesize that the mineralogical and amino acid composition of cetacean bullae differs from that of other bone because of (1) functional modifications for underwater sound reception and (2) structural adaptations related to rapid ossification.

Skeletal surveys in multiple myeloma

International Nuclear Information System (INIS)

Sebes, J.I.; Niell, H.B.; Palmieri, G.M.A.; Reidy, T.J.

1986-01-01

Thirty-three patients with multiple myeloma were studied with serial skeletal surveys, serum immunoglobulin levels, and postabsorptive urinary hydroxyproline (Spot-HYPRO) determinations. Twenty receiving chemotherapy were also followed with skeletal surveys in order to evaluate bone response to treatment. A close association was found between skeletal findings and changes in immunoglubulin levels with positive correlation in 71% of the patients. A similar association was found between skeletal disease and Spot-HYPRO level changes in 65%. Five of 12 patients (42%) with partial or complete clinical response to chemotherapy, demonstrated improvement in the appearance of skeletal lesions. Positive correlation between the roentgenographic changes and clinical markers of myeloma as well as therapeutic response, indicates that skeletal surveys are useful and effective in monitoring patients with multiple myeloma. (orig.)

The scapula as a window to the diagnosis of skeletal dysplasias

International Nuclear Information System (INIS)

Mortier, G.R.; Rimoin, D.L.; Lachman, R.S.

1997-01-01

Evaluation of the scapula can be useful in the diagnosis of skeletal dysplasias and helpful for the classification and delineation of new entities. A review of 2100 computerized cases of skeletal dysplasias in the International Skeletal Dysplasia Registry was performed. We found that the Luton type of platyspondylic lethal skeletal dysplasia differed radiographically from the San Diego type and Torrance type by the presence of two spikes at the inferior angle of the scapula. Hypoplasia of the body of the scapula, which is characteristic for campomelic dysplasia but not for kyphomelic dysplasia, is also present in Antley-Bixler syndrome. Radiographic and clinical similarities between campomelic dysplasia and Antley-Bixler syndrome suggest that they might be related disorders and that the latter condition should be included in the bent-bone dysplasia group. Similarity between the metaphyseal regions of the scapula and the metaphyses of the long tubular bones in the different types of short-rib polydactyly syndrome illustrates the importance of evaluation of the scapula in this group as well as in other well-defined or unknown osteochondrodysplasias. (orig.). With 8 figs

Early identification and intervention matters: A comprehensive review of current evidence and recommendations for the monitoring of bone health in patients with cancer.

Science.gov (United States)

Brodowicz, Thomas; Hadji, Peyman; Niepel, Daniela; Diel, Ingo

2017-12-01

Bone metastases are common in patients with advanced solid tumors, and many individuals experience debilitating skeletal-related events (SREs; e.g. pathologic fracture, hypercalcemia, radiotherapy or surgery to bone, and spinal cord compression). These events substantially affect disease outcomes, including survival and quality of life, and healthcare systems. Plain radiography is the most widely used imaging modality for the detection of bone metastases; skeletal scintigraphy, computed tomography, positron emission tomography and magnetic resonance imaging offer greater sensitivity but their use in routine practice is restricted by high costs and limited availability. Biomarkers of bone turnover may also have a role in the early detection of bone metastases and can provide valuable prognostic information on disease progression. SREs can be delayed or prevented using agents such as the receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, denosumab, and bisphosphonates. Painful bone metastases can be treated with radiofrequency ablation, radiotherapy, or radionuclides such as radium-223 dichloride, which has been shown to delay the onset of SREs in men with castration-resistant prostate cancer. Close monitoring of bone health in patients with advanced cancer may lead to early identification of individuals with bone metastases who could benefit from early intervention to prevent SREs. This review examines current guideline recommendations for assessing and monitoring bone health in patients with advanced cancer, use of biomarkers and treatment of patients with bone metastases. The emerging evidence for the potential survival benefit conferred by early intervention with denosumab and bisphosphonates is also discussed, together with best practice recommendations. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Distribution of skeletal malignancies in beagles injected with 239Pu citrate

International Nuclear Information System (INIS)

Lloyd, R.D.; Taylor, G.N.; Angus, W.

1994-01-01

The distribution of skeletal malignancies among our beagles injected with 239 Pu as young adults roughly seems to follow the distribution of skeletal mass and skeletal 239 Pu. These findings are similar to those we reported previously for a group of dogs given 226 Ra. Although there were differences in tumor distribution between the animals given 239 Ra and those given 239 Pu, most of them were not statistically significant; however, the radium dogs seemed to show a greater sensitivity to bone tumor origin in the tibia, while there may have been a tendency among the plutonium dogs toward increased relative sensitivity in the scapula, lumbar vertebrae, sacrum, and ribs. In contrast, the most common site for the formation of naturally-occurring bone malignancy in the dog is the distal radius. Perhaps there were too few tumors and too few dogs to establish statistical significance. A correlation between tumor location and at least two anatomical-physiological factors in the skeleton indicated that these two factors (site-specific bone turnover rate and percent of red marrow at the site, which is correlated with vascularity) may influence the appearance of malignancies both individually and in combination. Except for the femur, there appeared to be no difference between the relative distribution of skeletal malignancies of low-level (30 Bq-2 Bq kg -1 injected) and high-level (3-122 kBq kg -1 ) dogs. Distribution of bone tumors between the axial and appendicular skeleton was 50% vs. 50% for 239 Pu (42 and 42), but it was 39% axial vs. 61% appendicular (22 and 35, respectively) for dogs given 226 Ra. This difference was not significant (p > 0.2). 15 refs., 4 tabs

Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice.

Science.gov (United States)

Zhang, Y; Wang, L; Song, Y; Zhao, X; Wong, M S; Zhang, W

2016-03-01

The skeletal renin-angiotensin system contributes to the development of osteoporosis. The renin inhibitor aliskiren exhibited beneficial effects on trabecular bone of osteoporotic mice, and this action might be mediated through angiotensin and bradykinin receptor pathways. This study implies the potential application of renin inhibitor in the management for postmenopausal osteoporosis. The skeletal renin-angiotensin system plays key role in the pathological process of osteoporosis. The present study is designed to elucidate the effect of renin inhibitor aliskiren on trabecular bone and its potential action mechanism in ovariectomized (OVX) mice. The OVX mice were treated with low dose (5 mg/kg) or high dose (25 mg/kg) of aliskiren or its vehicle for 8 weeks. The bone turnover markers were measured by ELISA. The structural parameters of trabecular bone at lumbar vertebra (LV) and distal femoral metaphysis were measured by micro-CT. The expression of messenger RNA (mRNA) and protein was studied by RT-PCR and immunoblotting, respectively. Aliskiren treatment reduced urinary excretion of calcium and serum level of tartrate-resistant acid phosphatase in OVX mice. The treatment with aliskiren significantly increased bone volume (BV/TV) and connectivity density (Conn.D) of trabecular bone at LV-2 and LV-5 as well as dramatically enhanced BV/TV, Conn.D, bone mineral density (BMD/BV) and decreased bone surface (BS/BV) at the distal femoral end. Aliskiren significantly down-regulated the expression of angiotensinogen, angiotensin II (Ang II), Ang II type 1 receptor, bradykinin receptor (BR)-1, and osteocytic-specific gene sclerostin as well as the osteoclast-specific genes, including carbonic anhydrase II, matrix metalloproteinase-9, and cathepsin K. This study revealed that renin inhibitor aliskiren exhibited the beneficial effects on trabecular bone of ovariectomy-induced osteoporotic mice, and the underlying mechanism for this action might be mediated through Ang II and

Cost-effectiveness of denosumab versus zoledronic acid for preventing skeletal-related events in the Czech Republic.

Science.gov (United States)

Cristino, Joaquim; Finek, Jíndřich; Jandova, Petra; Kolek, Martin; Pásztor, Bálint; Giannopoulou, Christina; Qian, Yi; Brezina, Tomas; Lothgren, Mickael

2017-08-01

This study assessed the cost-effectiveness of the subcutaneous RANKL inhibitor, denosumab, vs the intravenous bisphosphonate, zoledronic acid, for the prevention of skeletal-related events (SREs) in patients with prostate cancer, breast cancer, and other solid tumors (OST) in the Czech Republic. A lifetime Markov model was developed to compare the effects of denosumab and zoledronic acid on costs (including drug costs and administration, patient management, SREs, and adverse events), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from a national payer perspective. Different discount rates, time horizons, SRE rates, distributions, and nature (asymptomatic vs all SREs), and the inclusion of treatment discontinuation were considered in scenario analyses. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Across tumor types, denosumab was associated with fewer SREs, improved QALYs, and higher total costs over a lifetime. The incremental cost per QALY gained for denosumab vs zoledronic acid was 382,673 CZK for prostate cancer, 408,450 CZK for breast cancer, and 608,133 CZK for OST. Incremental costs per SRE avoided for the same tumor type were 54,007 CZK, 51,765 CZK, and 94,426 CZK, respectively. In scenario analyses, the results remained similar to baseline, when different discount rates and time horizons were considered. At a non-official willingness-to-pay threshold of 1.2 million CZK, the probabilities of denosumab being cost-effective vs zoledronic acid were 0.64, 0.67, and 0.49 for prostate cancer, breast cancer, and OST, respectively. The SRE rates used were obtained from clinical trials; studies suggest rates may be higher in clinical practice. Additional evidence on real-world SRE rates could further improve the accuracy of the modeling. Compared with zoledronic acid, denosumab provides a cost-effective treatment option for the prevention of SREs in patients with prostate cancer

[Skeletal anchorage in the past, today and tomorrow].

Science.gov (United States)

Melsen, Birte; Dalstra, Michel

2017-03-01

Skeletal anchorage was not introduced as an alternative to conventional anchorage modalities. The first skeletal anchorage was a ligature through a hole in the infrazygomatic crest. This was replaced by surgical screws and finally the TADs, which were optimized with respect to the material and morphology, were developed. A bracket-like head allows for the use of the mini-implant as indirect anchorage, but should not be a tool for lost control resulting from badly planned biomechanics or failing compliance. Skeletal anchorage should serve as an adjunct to correct biomechanics, to enable treatments that could not be performed prior to the introduction of skeletal anchorage. The aim of this study was to test the hypothesis that temporary anchorage mini-screws help maintain bone density, height and width of alveolar processes in the extraction sites, and thus prevent the thinning of the alveolar ridge usually observed. In adult patients with degenerated dentitions the application of skeletal anchorage can allow for the displacement of teeth where no anchorage units are present, but also for the redevelopment and maintenance of atrophic alveolar bone. The basis for the optimal use of skeletal anchorage is that the correct line of action for the desired tooth displacement is defined and the necessary force system constructed either with the skeletal anchorage as direct or as indirect anchorage. After a period, during which osseointegrated implants were used as anchorage for tooth movement and bone maintenance, it was accepted that the mini-implants could serve also as anchorage for skeletal displacements avoiding loading of teeth. © EDP Sciences, SFODF, 2017.

Diagnostic imaging of skeletal metastases

International Nuclear Information System (INIS)

Scutellari, P. N.; Addonisio, G.; Righi, R.; Giganti, M.

2000-01-01

Purpose of this article is to present an algorithm for detection and diagnosis of skeletal metastases, which may be applied differently in symptomatic and asymptomatic cancer patients. February to March 1999 it was randomly selected and retrospectively reviewed the clinical charts of 100 cancer patients (70 women and 30 men; mean age: 63 years, range: 55-87). All the patients had been staged according to TNM criteria and had undergone conventional radiography and bone scan; when findings were equivocal, CT and MRI had been performed too. The primary lesions responsible for bone metastases were sited in the: breast (51 cases), colon (30 cases: 17 men and 13 women), lung (7 cases: 6 men and 1 woman), stomach (4 cases: 2 men and 2 women), skin (4 cases: 3 men and 1 woman), kidney (2 men), pleura (1 woman), and finally liver (1 man). The most frequent radiographic pattern was the lytic type (52%), followed by osteosclerotic, mixed, lytic vs mixed and osteosclerotic vs lytic patterns. The patients were divided into two groups: group A patients were asymptomatic and group B patients had local symptoms and/or pain. Skeletal metastases are the most common malignant bone tumors: the spine and the pelvis are the most frequent sites of metastasis, because of the presence of high amounts of red (hematopoietic active) bone marrow. Pain is the main symptom, even though many bone metastases are asymptomatic. Pathological fractures are the most severe consequences. With the algorithm for detection and diagnosis of skeletal metastases two different diagnostic courses are available for asymptomatic and symptomatic patients. Bone scintigraphy remains the technique of choice in asymptomatic patients in whom skeletal metastases are suspected. However this technique, though very sensitive, is poorly specific, and thus a negative bone scan finding is double-checked with another physical examination: if the findings remain negative, the diagnostic workup is over. On the contrary, in

Skeletal coccidioidomycosis: imaging findings in 19 patients

International Nuclear Information System (INIS)

Zeppa, M.A.; Greenspan, A.; McGahan, J.P.; Laorr, A.; Steinbach, L.S.

1996-01-01

The objective of this study was to describe the distribution and radiologic appearance of skeletal coccidioidomycosis in 19 documented cases. Medical records of 19 patients with clinically confirmed skeletal occidioidomycosis were retrospectively reviewed. The patients were studied with plain radiography, skeletal scintigraphy and MRI. Multiple lesions were seen in 11 of 19 patients (58%). Of a total of 46 lesions, 27 (59%) were described as punched-out lytic, 10 (22%) as permeative/destructive, and 9 (17%) as involving a joint and/or disk space. Lesions were identified in almost every bone (with the exception of the facial bones, ulna, carpus, and fibula) and were most commonly found in the axial skeleton (20 of 46; 43%). Plain radiographs are effective in the initial evaluation of bones and joints, scintigraphic studies can identify disseminated disease, and CT and MRI are effective in determining soft tissue involvement and spinal abnormalities. (orig./MG)

Objective evaluation of cervical vertebral bone age' its reliability in comparison with hand-wrist bone age: by TW3 method.

Science.gov (United States)

Prasad, Cms Krishna; Reddy, Vamsi Nilay; Sreedevi, Gojja; Ponnada, Swaroopa Rani; Priya, K Padma; Naik, B Raveendra

2013-09-01

The aim of this study was to establish the validity of a new method for evaluating skeletal maturation by assessing the 3rd and 4th cervical vertebrae seen in the cephalometric radiograph. This study consisted of a sample of 50 patients in the age group of 8 to 14 years of age. Chronologically, they were divided into six groups, based on the age consisting of a minimum of six to a maximum of 10 subjects. All the patients included in the study were females. The selected subjects were clinically examined and then age and date of birth of the patient in years and months was noted. Then lateral cephalograms and hand-wrist radiographs of the patient were taken on the same day with good clarity and contrast. The results suggested that cervical vertebral bone age on cephalometric radiographs calculated with this method is as reliable at estimating bone age as is the Tanner-Whitehouse 3 (TW3) method on hand-wrist radiographs. By determining the cervical vertebral bone age, skeletal maturity can be evaluated in a detailed and objective manner with cephalometric radiographs. The ability to accurately appraise skeletal maturity from cervical vertebral maturation, without the need for additional radiographs, has the potential to improve orthodontic diagnostic and therapeutic decisions. The technique's simplicity and ease of use should encourage this method as a frst level diagnostic tool to assess skeletal maturation. Clinical signifcance: This study revealed that the timing and sequence of ossifcation of the bones in hand and wrist and cervical vertebrae were able to relate the skeletal development of the various skeletal maturity indicators to a child's development. This method provided a mean with which one can determine the skeletal maturity of a person and thereby determine whether the possibility of potential growth existed.

Pharmacological Inhibition of Protein Kinase G1 Enhances Bone Formation by Human Skeletal Stem Cells Through Activation of RhoA-Akt Signaling

DEFF Research Database (Denmark)

Kermani, Abbas Jafari; Siersbaek, Majken S; Chen, Li

2015-01-01

for several malignant and nonmalignant conditions. We screened a library of kinase inhibitors to identify small molecules that enhance bone formation by human skeletal (stromal or mesenchymal) stem cells (hMSC). We identified H-8 (known to inhibit protein kinases A, C, and G) as a potent enhancer of ex vivo......Development of novel approaches to enhance bone regeneration is needed for efficient treatment of bone defects. Protein kinases play a key role in regulation of intracellular signal transduction pathways, and pharmacological targeting of protein kinases has led to development of novel treatments...

Quantitative CBCT evaluation of maxillary and mandibular cortical bone thickness and density variability for orthodontic miniplate placement.

Science.gov (United States)

Rossi, Margherita; Bruno, Giovanni; De Stefani, Alberto; Perri, Alessandro; Gracco, Antonio

2017-12-01

To assess whether cortical bone thickness and density vary in relation to age, sex and skeletal pattern at the maxillary and mandibular areas suitable for miniplates placement for orthodontic purposes. CBCT of 92 subjects (42 males and 50 females) with skeletal class I, II or III malocclusion, divided between adolescents and adults, were examined. InVivoDental ® software (Anatomage Inc, USA) was used to measure 34 maxillary areas and 40 mandibular areas per side. Values obtained were then compared between the groups of subjects. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney rank-sum test for independent samples. No significant differences were found in the cortical bone thickness values between the three skeletal patterns, and according to sex and age. Both maxilla and mandible showed an increase in cortical bone thickness from the anterior towards the posterior regions, and from the alveolar boneto the basal bone. Cortical bone density significantly varied in relation to the subject's age, with adults always showing higher values. Slight clinically significant differences were found between the three skeletal patterns and sex. In terms of cortical bone thickness, age, sex and skeletal pattern do not represent valid decision criteria for the evaluation of the best insertion areas for miniplates, while in terms of cortical bone density, only age is useful as a decision criterion. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

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 agi...

Skeletal scintigraphic changes in osteoporosis treated with sodium fluoride: concise communication

International Nuclear Information System (INIS)

Schulz, E.E.; Libanati, C.R.; Farley, S.M.; Kirk, G.A.; Baylink, D.J.

1984-01-01

An appendicular skeletal response to sodium fluoride (NaF) was detected by total skeletal scintigrams. Twelve postmenopausal osteoporotic women were treated with NaF (88 mg/day) and calcium (1500 mg/day). Total skeletal scintigrams were obtained before and during treatment. Within 4 to 21 mo (mean: 8.3), all 12 patients showed new areas of increased uptake corresponding to metaphyseal regions and short bones of the appendicular skeleton. Nine patients showed an increase in serum alkaline phosphatase activity, which was attributed to an increase in the skeletal isoenzyme. Seven of 12 patients developed bone pain in one or more of the regions of increased uptake. This study establishes that the skeletal scintigram is a sensitive index of the peripheral skeletal response to NaF

Mouse models of telomere dysfunction phenocopy skeletal changes found in human age-related osteoporosis

Directory of Open Access Journals (Sweden)

Tracy A. Brennan

2014-05-01

Full Text Available A major medical challenge in the elderly is osteoporosis and the high risk of fracture. Telomere dysfunction is a cause of cellular senescence and telomere shortening, which occurs with age in cells from most human tissues, including bone. Telomere defects contribute to the pathogenesis of two progeroid disorders characterized by premature osteoporosis, Werner syndrome and dyskeratosis congenital. It is hypothesized that telomere shortening contributes to bone aging. We evaluated the skeletal phenotypes of mice with disrupted telomere maintenance mechanisms as models for human bone aging, including mutants in Werner helicase (Wrn−/−, telomerase (Terc−/− and Wrn−/−Terc−/− double mutants. Compared with young wild-type (WT mice, micro-computerized tomography analysis revealed that young Terc−/− and Wrn−/−Terc−/− mice have decreased trabecular bone volume, trabecular number and trabecular thickness, as well as increased trabecular spacing. In cortical bone, young Terc−/− and Wrn−/−Terc−/− mice have increased cortical thinning, and increased porosity relative to age-matched WT mice. These trabecular and cortical changes were accelerated with age in Terc−/− and Wrn−/−Terc−/− mice compared with older WT mice. Histological quantification of osteoblasts in aged mice showed a similar number of osteoblasts in all genotypes; however, significant decreases in osteoid, mineralization surface, mineral apposition rate and bone formation rate in older Terc−/− and Wrn−/−Terc−/− bone suggest that osteoblast dysfunction is a prominent feature of precocious aging in these mice. Except in the Wrn−/− single mutant, osteoclast number did not increase in any genotype. Significant alterations in mechanical parameters (structure model index, degree of anistrophy and moment of inertia of the Terc−/− and Wrn−/−Terc−/− femurs compared with WT mice were also observed. Young Wrn�

Strategic camouflage treatment of skeletal Class III malocclusion (mandibular prognathism) using bone-borne rapid maxillary expansion and mandibular anterior subapical osteotomy.

Science.gov (United States)

Seo, Yu-Jin; Lin, Lu; Kim, Seong-Hun; Chung, Kyu-Rhim; Nelson, Gerald

2016-01-01

This case report presents the camouflage treatment that successfully improved the facial profile of a patient with a skeletal Class III malocclusion using bone-borne rapid maxillary expansion and mandibular anterior subapical osteotomy. The patient was an 18-year-old woman with chief complaints of crooked teeth and a protruded jaw. Camouflage treatment was chosen because she rejected orthognathic surgery under general anesthesia. A hybrid type of bone-borne rapid maxillary expander with palatal mini-implants was used to correct the transverse discrepancy, and a mandibular anterior subapical osteotomy was conducted to achieve proper overjet with normal incisal inclination and to improve her lip and chin profile. As a result, a Class I occlusion with a favorable inclination of the anterior teeth and a good esthetic profile was achieved with no adverse effects. Therefore, the hybrid type of bone-borne rapid maxillary expander and a mandibular anterior subapical osteotomy can be considered effective camouflage treatment of a skeletal Class III malocclusion, providing improved inclination of the dentition and lip profile. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Current options for the treatment of Paget’s disease of the bone

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Daniela Merlotti

2009-07-01

Full Text Available Daniela Merlotti, Luigi Gennari, Giuseppe Martini, Ranuccio NutiDepartment of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, ItalyAbstract: Paget’s disease of bone (PDB is a chronic bone remodeling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an incidence of less than 1%, but has a grave prognosis. Specific therapy for PDB is aimed at decreasing the abnormal bone turnover and bisphosphonates are currently considered the treatment of choice. These treatments are associated with a reduction in plasma alkaline phosphatase (ALP activity and an improvement in radiological and scintigraphic appearance and with a reduction in bone pain and bone deformity, Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more effective and convenient management of this debilitating disorder.Keywords: Paget’s disease of bone, bisphosphonates, aminobisphosphonates, bone remodeling

 Age-related changes of skeletal muscles: physiology, pathology and regeneration

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Aleksandra Ławniczak

2012-06-01

Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

A physiological skeletal model for radionuclide and stable element biokinetics in children and adults

International Nuclear Information System (INIS)

Richardson, R.B.

2010-01-01

A physiological skeletal model (PSM) is described that represents the skeletal uptake, retention and clearance of both bone-surface-seeking and bone-volume-seeking radionuclides and stable elements. A key objective of the PSM is to model the higher skeletal growth and bone turnover in infants and children (compared to adults) in order to to account for their greater uptake and cancer risk from bone-seeking contaminants such as lead and plutonium. The PSM is a compartmental model that allows for the incorporation of organic and inorganic material in the bone volume via quiescent bone surfaces, forming bone surfaces and the lacuno-canaliculi system. The model uniquely incorporates a tertiary phase of mineralization via bone fluids. The PSM's structural concepts and biokinetic parameters - such as realistic mass transfers, organ and tissue masses, and bone remodelling half times - are selected mainly on the basis of physiological and anatomical criteria. For brevity, model parameter values or evaluated for adults only. The PSM is an improvement on existing skeletal models that are based more on compartment structures and pathways that rendered good fits to biokinetic data rather than on being anatomically and physiologically accurate. (author)

Zoledronic acid enhances the effect of radiotherapy for bone metastases from renal cell carcinomas. More than a 24-month median follow-up

International Nuclear Information System (INIS)

Takeda, Naoki; Isu, Kazuo; Hiraga, Hiroaki; Shinohara, Nobuo; Minami, Akio; Kamata, Hajime

2012-01-01

Renal cell carcinoma (RCC) is thought to respond unreliably to radiotherapy (RT). Zoledronic acid significantly reduces the risk of skeletal complications. This study investigated whether RT with zoledronic acid prolonged the time to bone-lesion progression in comparison with RT alone. Twenty-seven patients (34 lesions) with bone metastases secondary to RCC undergoing treatment with RT with or without zoledronic acid were retrospectively evaluated at two institutions between 1999 and 2009. Twelve patients were treated with RT alone from 1999 to 2008 (RT group). Fifteen patients were treated with RT and zoledronic acid from 2006 to 2009 (RT+Z group). The time to skeletal-related events and pain progression were assessed from patients' medical records. The median (range) follow-up was 26 (3-75) and 24 (3-55) months in the RT and RT+Z groups, respectively. Three patients (three lesions) in the RT+Z group had skeletal-related events (SREs). In contrast, six patients (eight lesions) in the RT group had SREs. SREs comprised pathological fractures in five, additional surgeries in three, spinal cord or cauda equine compression in two, and repeat RT in one. There was a significant difference in SRE-free survival time and duration of site-specific pain response between groups. RT combined with zoledronic acid significantly prolonged SRE-free survival and duration of pain response compared with RT alone in the treatment of osseous metastases from RCC. (author)

99mTc-MDP bone scintigraphy findings representing osteoporosis

International Nuclear Information System (INIS)

Nam, Dae Gun; Moon, Tae Geon; Kim, Ji Hong; Son, Seok Man; Kim, In Ju; Kim, Yong Ki

2001-01-01

Bone scintigraphy with 99m Tc-labeled phosphates is one of the most common procedures in evaluation of various skeletal disorders. Metabolic bone diseases show involvement of the whole skeleton and are associated with increased bone turnover and increased uptake of 99m Tc-labeled phosphates. In this study, we investigated apparently normal women who were examined with routine bone scintigraphy applied bone densitometry to correlate it with skeletal uptake in bone scan. This study includes 79 women who were performed both of bone mineral density(BMD) and bone scintigraphy. We investigated the relation of bone scan findings and BMD of lumbar, femur, radius. Regional BMD were negatively correlated with increased age. Among the bone scintigraphy findings representing metabolic bone disease, uptakes by the long bones, skull and mandible increased with age in women, while that in the costochondral junction decreased. Increased skull and mandible uptakes is associated with decreased BMD, and it has statistically significance. Our results show that increased radionuclide uptake in bone scintigraphy, especially skull and mandible uptake was associated with decreased lumbar, femur BMD in women. So that, increased skull and mandible uptake in women would be a scintigraphic sign of osteopenia or osteoporosis

The Evolution of Trans-Skeletal Method Osteosynthesis | Omeonu ...

African Journals Online (AJOL)

OBJECTIVE: The purpose of this article is to give a brief overview of the history of trans-skeletal method ostheosynthesis as it relates to the evolution of the Ilizarov external fixation device. BODY: The pin frame external fixators originated from the idea of bone reduction with pins fixed to fragments before applying the plaster ...

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

International Nuclear Information System (INIS)

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

1976-01-01

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

Prader-Willi Critical Region, a Non-Translated, Imprinted Central Regulator of Bone Mass: Possible Role in Skeletal Abnormalities in Prader-Willi Syndrome.

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Ee-Cheng Khor

Full Text Available Prader-Willi Syndrome (PWS, a maternally imprinted disorder and leading cause of obesity, is characterised by insatiable appetite, poor muscle development, cognitive impairment, endocrine disturbance, short stature and osteoporosis. A number of causative loci have been located within the imprinted Prader-Willi Critical Region (PWCR, including a set of small non-translated nucleolar RNA's (snoRNA. Recently, micro-deletions in humans identified the snoRNA Snord116 as a critical contributor to the development of PWS exhibiting many of the classical symptoms of PWS. Here we show that loss of the PWCR which includes Snord116 in mice leads to a reduced bone mass phenotype, similar to that observed in humans. Consistent with reduced stature in PWS, PWCR KO mice showed delayed skeletal development, with shorter femurs and vertebrae, reduced bone size and mass in both sexes. The reduction in bone mass in PWCR KO mice was associated with deficiencies in cortical bone volume and cortical mineral apposition rate, with no change in cancellous bone. Importantly, while the length difference was corrected in aged mice, consistent with continued growth in rodents, reduced cortical bone formation was still evident, indicating continued osteoblastic suppression by loss of PWCR expression in skeletally mature mice. Interestingly, deletion of this region included deletion of the exclusively brain expressed Snord116 cluster and resulted in an upregulation in expression of both NPY and POMC mRNA in the arcuate nucleus. Importantly, the selective deletion of the PWCR only in NPY expressing neurons replicated the bone phenotype of PWCR KO mice. Taken together, PWCR deletion in mice, and specifically in NPY neurons, recapitulates the short stature and low BMD and aspects of the hormonal imbalance of PWS individuals. Moreover, it demonstrates for the first time, that a region encoding non-translated RNAs, expressed solely within the brain, can regulate bone mass in health

Unicameral Bone Cyst of the Medial Cuneiform: A Case Report.

Science.gov (United States)

Schick, Faith A; Daniel, Joseph N; Miller, Juliane S

2016-02-17

A unicameral bone cyst is a relatively uncommon, benign bone tumor found in the metaphysis of long bones, such as the humerus and the femur, in skeletally immature persons. In the foot, these benign, fluid-filled cavities are most commonly found within the os calcis. We present a case report of a 10-year-old female with a unicameral bone cyst of the medial cuneiform.

Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.

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John P Kemp

2014-06-01

Full Text Available Heritability of bone mineral density (BMD varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg and residual (re correlations between BMD measured at the upper limbs (UL-BMD, lower limbs (LL-BMD and skull (SK-BMD, using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC. Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78 between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43. Likewise, the residual correlation between BMD at appendicular sites (r(e = 0.55 was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e = 0.20-0.24. To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395, combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites. In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37, whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14. In addition, we report a novel association between RIN3 (previously associated with Paget's disease and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10. Our results suggest that BMD at different skeletal sites is under a mixture of shared and

Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.

Science.gov (United States)

Kemp, John P; Medina-Gomez, Carolina; Estrada, Karol; St Pourcain, Beate; Heppe, Denise H M; Warrington, Nicole M; Oei, Ling; Ring, Susan M; Kruithof, Claudia J; Timpson, Nicholas J; Wolber, Lisa E; Reppe, Sjur; Gautvik, Kaare; Grundberg, Elin; Ge, Bing; van der Eerden, Bram; van de Peppel, Jeroen; Hibbs, Matthew A; Ackert-Bicknell, Cheryl L; Choi, Kwangbom; Koller, Daniel L; Econs, Michael J; Williams, Frances M K; Foroud, Tatiana; Zillikens, M Carola; Ohlsson, Claes; Hofman, Albert; Uitterlinden, André G; Davey Smith, George; Jaddoe, Vincent W V; Tobias, Jonathan H; Rivadeneira, Fernando; Evans, David M

2014-06-01

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and

Zoledronic acid use in patients with bone metastases from renal cell carcinoma or bladder cancer.

Science.gov (United States)

Saad, Fred; Eastham, James A

2010-06-01

Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients with bladder cancer develop bone metastases that can disrupt normal bone homeostasis and place patients at risk for potentially life-limiting skeletal-related events (SREs). In the absence of bone-directed therapies, patients with RCC may experience up to four SREs per year. In patients with bone metastases from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk of SREs compared with placebo. In addition to its bone-protective effects, preclinical and early clinical evidence indicates that ZOL prevents tumor progression. For example, retrospective subset analysis in patients with RCC indicated that ZOL extended time to disease progression and demonstrated a trend toward improved overall survival compared with placebo. Additionally, a study in patients with bone metastases from bladder cancer demonstrated that ZOL improved 1-year overall survival compared with placebo. Bone metastases place a heavy burden on patients with RCC or bladder cancer, and early, continuous treatment with ZOL may provide anticancer benefits in addition to important patient quality of life. 2010. Published by Elsevier Inc.

Luminol testing in detecting modern human skeletal remains: a test on different types of bone tissue and a caveat for PMI interpretation.

Science.gov (United States)

Caudullo, Giorgio; Caruso, Valentina; Cappella, Annalisa; Sguazza, Emanuela; Mazzarelli, Debora; Amadasi, Alberto; Cattaneo, Cristina

2017-01-01

When forensic pathologists and anthropologists have to deal with the evaluation of the post-mortem interval (PMI) in skeletal remains, luminol testing is frequently performed as a preliminary screening method. However, the repeatability of this test on the same bone, as well as comparative studies on different bones of the same individual, has never been performed. Therefore, with the aim of investigating the influence that different types of bones may exert on the response to the luminol test, the present study analysed three different skeletal elements (femoral diaphysis, vertebra and cranial vault), gathered from ten recent exhumed skeletons (all with a 20-year PMI). The analysis was performed twice on the same bone after 2 months: the analysis at time 0 concerned the whole bone, whereas the second concerned only a part of the same bone taken during the first test (which already had been broken). The overall results showed different responses, depending on the type of bone and on the integrity of the samples. Negative results at the first analysis (6.6% out of the total of samples) are consistent with what is reported in the literature, whilst at the second analysis, the increase of about 20% of false-negative results highlights that the luminol test ought to be performed with caution in case of broken bones or elements which are taphonomically altered. Results have thus proven that the exposition to environmental agents might result in haemoglobin (Hb) loss, as detected even after only 2 months. The study also focused on the crucial issue of the type of bone subjected to testing, remarking the suitability of the femoral diaphysis (100% of positive responses at the first analysis vs only 18% of false-negative results at the second test, corresponding to 5% of total false-negative results) as opposed to other bone elements that showed a low yield. In particular, the cranial vault gave poor results, with 40% of discrepancy between results from the two analyses

Mitigating HZE Radiation-Induced Deficits in Marrow-Derived Mesenchymal Progenitor Cells and Skeletal Structure

Science.gov (United States)

Globus, Ruth K.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Terada, Masahiro; Alwood, Joshua; Halloran, Bernard; Tahimic, Candice

2016-01-01

Future long-duration space exploration 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 causes 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.

A comparison of hand-wrist bone and cervical vertebral analyses in measuring skeletal maturation.

Science.gov (United States)

Gandini, Paola; Mancini, Marta; Andreani, Federico

2006-11-01

To compare skeletal maturation as measured by hand-wrist bone analysis and by cervical vertebral analysis. A radiographic hand-wrist bone analysis and cephalometric cervical vertebral analysis of 30 patients (14 males and 16 females; 7-18 years of age) were examined. The hand-wrist bone analysis was evaluated by the Bjork index, whereas the cervical vertebral analysis was assessed by the cervical vertebral maturation stage (CVMS) method. To define vertebral stages, the analysis consisted of both cephalometric (13 points) and morphologic evaluation of three cervical vertebrae (concavity of second, third, and fourth vertebrae and shape of third and fourth vertebrae). These measurements were then compared with the hand-wrist bone analysis, and the results were statistically analyzed by the Cohen kappa concordance index. The same procedure was repeated after 6 months and showed identical results. The Cohen kappa index obtained (mean +/- SD) was 0.783 +/- 0.098, which is in the significant range. The results show a concordance of 83.3%, considering that the estimated percentage for each case is 23.3%. The results also show a correlation of CVMS I with Bjork stages 1-3 (interval A), CVMS II with Bjork stage 4 (interval B), CVMS III with Bjork stage 5 (interval C), CVMS IV with Bjork stages 6 and 7 (interval D), and CVMS V with Bjork stages 8 and 9 (interval E). Vertebral analysis on a lateral cephalogram is as valid as the hand-wrist bone analysis with the advantage of reducing the radiation exposure of growing subjects.

Dense bone - too much bone: Radiological considerations and differential diagnosis. Pt. 2

Energy Technology Data Exchange (ETDEWEB)

Jacobson, H.G.

1985-02-01

In conclusion, the attempt has been made to demonstrate that three major forms of new bone formation exist: reactive, neoplastic, and the newborn or relative skeletal sclerosis in congenital (developmental) disorders. A classification of skeletal disorders has been presented and four major groups have been selected from the nine categories in this classification. These are: congenital-developmental, metabolic and endocrine, benign neoplasms and malignant neoplasms. In all four categories a large group of entities which may present with new bone (sclerosis) are listed and are discussed in some, but limited, detail. A number of these entities in each of the four categories are illustrated. Some difficulty is encountered in considering the mechanisms for the production of bony sclerosis in the group of congenital-developmental disorders. In such entities as osteopetrosis, the overproduction of cartilage cords and subsequent excessive mineralization is known to be responsible for the dense bone. However, in various skeletal dysplasias (e.g. pyknodysostosis, van Bucherm disease), the exact mechanism for the development of the diffuse sclerotic process is not clearly understood. In the metabolic and endocrine category, the situation as to mechanism is less unclear in considering the reason for the development of bony sclerosis. Yet even in evaluating disorders such as renal osteodystrophy, the reactive bony sclerosis in the presence of secondary hyperparathyroidism and osteomalacia is a source of speculation with no definite proof, as yet.

The Role Of Semaphorin 3A In The Skeletal System.

Science.gov (United States)

Tang, Peifu; Yin, Pengbin; Lv, Houchen; Zhang, Licheng; Zhang, Lihai

2015-01-01

Semaphorin 3A (Sema3A), characterized by a conserved N-terminal "Sema" domain, was originally described as an axon guidance molecule. Recent research indicates that it performs a critical function in the skeletal system. This review highlights recent advances in understanding of the role of Sema3A in the skeletal system as a regulator of bone metabolism and as a potential drug target for bone disease therapy. We summarize Sema3A functions in osteoblastogenesis and osteoclastogenesis, as well as in innervation, and we discuss its multifunctional role in various bone diseases such as osteoporosis and low back pain. Despite limited research in this field, our aim is to promote further understanding of the function of Sema3A in the skeletal system.

Methods and theory in bone modeling drift: comparing spatial analyses of primary bone distributions in the human humerus.

Science.gov (United States)

Maggiano, Corey M; Maggiano, Isabel S; Tiesler, Vera G; Chi-Keb, Julio R; Stout, Sam D

2016-01-01

This study compares two novel methods quantifying bone shaft tissue distributions, and relates observations on human humeral growth patterns for applications in anthropological and anatomical research. Microstructural variation in compact bone occurs due to developmental and mechanically adaptive circumstances that are 'recorded' by forming bone and are important for interpretations of growth, health, physical activity, adaptation, and identity in the past and present. Those interpretations hinge on a detailed understanding of the modeling process by which bones achieve their diametric shape, diaphyseal curvature, and general position relative to other elements. Bone modeling is a complex aspect of growth, potentially causing the shaft to drift transversely through formation and resorption on opposing cortices. Unfortunately, the specifics of modeling drift are largely unknown for most skeletal elements. Moreover, bone modeling has seen little quantitative methodological development compared with secondary bone processes, such as intracortical remodeling. The techniques proposed here, starburst point-count and 45° cross-polarization hand-drawn histomorphometry, permit the statistical and populational analysis of human primary tissue distributions and provide similar results despite being suitable for different applications. This analysis of a pooled archaeological and modern skeletal sample confirms the importance of extreme asymmetry in bone modeling as a major determinant of microstructural variation in diaphyses. Specifically, humeral drift is posteromedial in the human humerus, accompanied by a significant rotational trend. In general, results encourage the usage of endocortical primary bone distributions as an indicator and summary of bone modeling drift, enabling quantitative analysis by direction and proportion in other elements and populations. © 2015 Anatomical Society.

Bone marrow mesenchymal cells improve muscle function in a skeletal muscle re-injury model.

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Bruno M Andrade

Full Text Available Skeletal muscle injury is the most common problem in orthopedic and sports medicine, and severe injury leads to fibrosis and muscle dysfunction. Conventional treatment for successive muscle injury is currently controversial, although new therapies, like cell therapy, seem to be promise. We developed a model of successive injuries in rat to evaluate the therapeutic potential of bone marrow mesenchymal cells (BMMC injected directly into the injured muscle. Functional and histological assays were performed 14 and 28 days after the injury protocol by isometric tension recording and picrosirius/Hematoxilin & Eosin staining, respectively. We also evaluated the presence and the fate of BMMC on treated muscles; and muscle fiber regeneration. BMMC treatment increased maximal skeletal muscle contraction 14 and 28 days after muscle injury compared to non-treated group (4.5 ± 1.7 vs 2.5 ± 0.98 N/cm2, p<0.05 and 8.4 ± 2.3 vs. 5.7 ± 1.3 N/cm2, p<0.05 respectively. Furthermore, BMMC treatment increased muscle fiber cross-sectional area and the presence of mature muscle fiber 28 days after muscle injury. However, there was no difference in collagen deposition between groups. Immunoassays for cytoskeleton markers of skeletal and smooth muscle cells revealed an apparent integration of the BMMC within the muscle. These data suggest that BMMC transplantation accelerates and improves muscle function recovery in our extensive muscle re-injury model.

Bone-seeking /sup 99m/Tc complex

International Nuclear Information System (INIS)

Subramanian, G.; McAfee, J.G.

1977-01-01

A bone-seeking, technetium-99m-tin-phosphonate complex effective as a skeletal-imaging agent has been found particularly useful for diagnostic purposes. Skeletal tissue concentrations or technetium-99m obtained with the complex compare favorably to other bone-seeking radionuclides

Radiogrammetric analysis of upper limb long bones

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Stojanović Zlatan

2011-01-01

Full Text Available Radiogrammetry is radiological method of bone mineral density quantification. Besides giving an insight in diagnostics and evolution of metabolic bone disorders (osteoporosis, osteomalacia, osteitis deformans- Paget's disease, it can also explain some specific biomechanical characteristics of bone structures. The aim of this study is to evaluate the significance and perspectives of radiogrammetry as a scientific model for further inquiry of skeletal system. The work demonstrates mathematical parameters (Ca-Cortical area, CI- Cortical index, GI- Garn's index, ESI- Exton Smith's index of upper limb long bones (humerus, radius, ulna. Two standard radiological projections of bones were taken: antero-posterior (AP and latero-lateral (LL. Correlation with metacarpal and lower limb bones was also performed. The value of the cortical area of humerus is significantly higher comparing with the two other examined bones (Xmean 2,2443 cm2, p < 0.01. Radial bone has the highest values of the relational mathematical parameters, which implicates its higher strength by volumetric unit concerning humerus and ulna. Despite the development of contemporary osteometric procedures (ultrasound densitometry, dual X-ray absorptiometry, digital X-ray radiogrammetry, the classical radiogrammetry sustains its important role in diagnostics of metabolic bone disorders and it can be successfully used for biomechanical inquiry of skeletal system.

The effect of Hydroxyapatite/collagen I composites, bone marrow aspirate and bone graft on fixation of bone implants in sheep

DEFF Research Database (Denmark)

Babiker, Hassan

  The effect of Hydroxyapatite/collagen I composites, bone marrow aspirate and bone graft on fixation of bone implants IN SHEEP   Ph.D. Student, Hassan Babiker; Associate Professor, Ph.D. Ming Ding; Professor, dr.med., Soren Overgaard. Department of Orthopaedic Surgery, Odense University Hospital......, Odense, Denmark   Background: Hydroxyapatite and collagen composites (HA/coll) have the potential in mimicking and replacing skeletal bones. This study attempted to determine the effect of newly developed HA/coll-composites with and without bone marrow aspirate (BMA) in order to enhance the fixation...... of bone implants.   Materials and Methods: Titanium alloy implants were inserted into bilateral femoral condyles of 8 skeletally mature sheep, four in each sheep. The implant has a circumferential gap of 2 mm. The gap was filled with: HA/coll; HA/coll-BMA; autograft or allograft. Allograft was served...

Traumatic skeletal changes

International Nuclear Information System (INIS)

Troeger, J.; Schofer, O.

1985-01-01

Skeleton scintiscanning is indicated in the following cases: (1) Suspected bone injury after clinical examination, the radiograph of the skeletal region in question contributing findings that either do not confirm suspision, or make not clear whether the changes observed are traumatic. (2) Polytrauma. (3) When the accident scenario reported by the persons taking care of the child does not sufficiently explain the skeletal changes observed, or when these persons expressly deny the possibility of a trauma being the cause of findings observed. (4) Suspected or proven battered-child syndrome. (orig./MG) [de

Diffuse lymphangiomatosis of bone

International Nuclear Information System (INIS)

Maki, D.D.; Nesbit, M.E.; Griffiths, H.J.

1999-01-01

Two cases of lymphangiomatosis of bone, a very rare systemic condition characterised by both skeletal and parenchymal lesions, are presented. The skeletal changes have an appearance similar to haemangiomas in the spine, and soap-bubbly lesions in the flat bones. One case carried the diagnosis of eosinophilic granuloma for 18 years. The findings on MRI, which have not been previously well-established, are discussed. Copyright (1999) Blackwell Science Pty Ltd

Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma

International Nuclear Information System (INIS)

Ehara, Shigeru; Nishida, Jun; Shiraishi, Hideo; Yoshioka, Hiroshi; Okada, Kyoji; Sumiya, Hisashi; Takano, Hideyuki

2007-01-01

The objective was to elucidate clinical and imaging features of skeletal involvement, recurrences, and metastases of extraskeletal myxoid chondrosarcoma. Included in this series are 4 patients, aged 44 to 65 years, 3 of whom were men and 1 a woman. The primary lesions were in the thigh (n 3) and the upper arm (n = 1). Three patients with multiple metastases died of the disease, 2 were considered to have local recurrence in the adjacent bone. Skeletal metastases occurred after lung metastases in 2 cases, and before lung metastases in 1 case. Typical imaging findings are well-defined lesions with no sclerotic margin or matrix mineralization. A slow, but persistent growth is noted on the imaging features. Although skeletal metastases of chondrosarcoma of bone and soft tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain differentiation, rarely metastasize and/or recur in the bones. The imaging features are typically of a localized lesion with cortical disruption or expansion. (orig.)

Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma

Energy Technology Data Exchange (ETDEWEB)

Ehara, Shigeru [Iwate Medical University School of Medicine, Department of Radiology, Morioka (Japan); Nishida, Jun; Shiraishi, Hideo [Iwate Medical University School of Medicine, Department of Orthopedic Surgery, Iwate (Japan); Yoshioka, Hiroshi [University of Tsukuba School of Medicine, Department of Radiology, Tsukuba (Japan); Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Okada, Kyoji [Akita University School of Medicine, Department of Orthopedic Surgery, Akita (Japan); Sumiya, Hisashi [Kanazawa University School of Medicine, Department of Nuclear Medicine, Kanazawa (Japan); Yawata Medical Center, Komatsu (Japan); Takano, Hideyuki [Chiba Cancer Center, Division of Diagnostic Imaging, Chiba (Japan)

2007-09-15

The objective was to elucidate clinical and imaging features of skeletal involvement, recurrences, and metastases of extraskeletal myxoid chondrosarcoma. Included in this series are 4 patients, aged 44 to 65 years, 3 of whom were men and 1 a woman. The primary lesions were in the thigh (n = 3) and the upper arm (n = 1). Three patients with multiple metastases died of the disease, 2 were considered to have local recurrence in the adjacent bone. Skeletal metastases occurred after lung metastases in 2 cases, and before lung metastases in 1 case. Typical imaging findings are well-defined lesions with no sclerotic margin or matrix mineralization. A slow, but persistent growth is noted on the imaging features. Although skeletal metastases of chondrosarcoma of bone and soft tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain differentiation, rarely metastasize and/or recur in the bones. The imaging features are typically of a localized lesion with cortical disruption or expansion. (orig.)

Association of stressful life events with accelerated bone loss in older men: the Osteoporotic Fractures in Men (MrOS) Study

Science.gov (United States)

Fink, Howard A.; Kuskowski, Michael A.; Cauley, Jane A.; Taylor, Brent C.; Schousboe, John T.; Cawthon, Peggy M.; Ensrud, Kristine E.

2015-01-01

Purpose/Introduction Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss. Methods 4388 men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (>1 SD more than mean annualized change). Results 75.3% of men reported ≥1 type of stressful life event, including 43.3% with ≥2 types of stressful life events. Mean annualized BMD loss was −0.36% (SD 0.88) and 13.9% of men were categorized with accelerated BMD loss (about 5.7% or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (pstressful life events (RR, 1.10 [95% CI, 1.04–1.16]) per increase of 1 type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p=0.08). Conclusions In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association. PMID:25169421

Skeletal (stromal) stem cells

DEFF Research Database (Denmark)

Abdallah, Basem M; Kermani, Abbas Jafari; Zaher, Walid

2015-01-01

Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy....../preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone....

Skeletal dosimetry models for alpha-particles for use in molecular radiotherapy

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Watchman, Christopher J.

Molecular radiotherapy is a cancer treatment methodology whereby a radionuclide is combined with a biologically active molecule to preferentially target cancer cells. Alpha-particle emitting radionuclides show significant potential for use in molecular radiotherapy due to the short range of the alpha-particles in tissue and their high rates of energy deposition. Current radiation dosimetry models used to assess alpha emitter dose in the skeleton were developed originally for occupational applications. In medical dosimetry, individual variability in uptake, translocation and other biological factors can result in poor correlation of clinical outcome with marrow dose estimates determined using existing skeletal models. Methods presented in this work were developed in response to the need for dosimetry models which account for these biological and patient-specific factors. Dosimetry models are presented for trabecular bone alpha particle dosimetry as well as a model for cortical bone dosimetry. These radiation transport models are the 3D chord-based infinite spongiosa transport model (3D-CBIST) and the chord-based infinite cortical transport model (CBICT), respectively. Absorbed fraction data for several skeletal tissues for several subjects are presented. Each modeling strategy accounts for biological parameters, such as bone marrow cellularity, not previously incorporated into alpha-particle skeletal dosimetry models used in radiation protection. Using these data a study investigating the variability in alpha-particle absorbed fractions in the human skeleton is also presented. Data is also offered relating skeletal tissue masses in individual bone sites for a range of ages. These data are necessary for dose calculations and have previously only been available as whole body tissue masses. A revised 3D-CBIST model is also presented which allows for changes in endosteum thickness to account for revised target cell location of tissues involved in the radiological

Age-related differences in the bone mineralization pattern of rats following exercise

International Nuclear Information System (INIS)

McDonald, R.; Hegenauer, J.; Saltman, P.

1986-01-01

The effect of 12 weeks of treadmill exercise on the mineralization of trabecular and cortical bone was studied in rats 7, 14, and 19 months of age. Bone mineralization was evaluated by measuring concentrations of Ca, Mg, and hydroxyproline as well as uptake of 45Ca concentration in the femur, humerus, rib and calvaria. The 7- and 14-month-old rats increased mineralization in those cortical bones directly involved in exercise. The 19-month animal responded to exercise by increasing mineralization in all bones examined, including the nonweight bearing trabecular calvaria and cortical rib. From these data, it is apparent that the older animals undergo a total skeletal mineralization in response to exercise compared with local adaptation in the younger animal. Further, we provide evidence to support the use of the rat as a model in which to study mammalian bone physiology during the aging process

Skeletal changes in congenital fibrinogen abnormalities

Energy Technology Data Exchange (ETDEWEB)

Lagier, R.; Bouvier, C.A.; van Strijthem, N.

1980-01-01

We report anatomico-radiologic study of humerus, femur, and tibia from a case of total congenital afibrinogenemia. Juxtatrabecular hemorrhages occur mainly in metaphyses and seem to be related to normal lines of stress. They may lead to the formation of intraosseous cysts and to a remodelling of bone trabeculae. The radiologic lesions in a second case, diagnosed as congenital dysfibrinogenemia, are similar to those found in Case 1 (femoral trabeculae remodelling) but also resemble some alterations described in hemophilia (pseudotumor of the right iliac bone). Anatomic study of the lesions in Case 2 was not possible. The significance of these observations could be better defined by a more extended skeletal study (radiologic and when feasible anatomic) of patients with congenital clotting defects and especially with inherited disorders of the fibrinogen molecule. It would also be worthwhile investigating manifest or latent hemostatic disorders (particularly at the fibrinogen level) in patients with solitary or aneurysmal bone cysts, and even with bone infarct or unexplained trabecular remodelling.

Increased bone radiotracer uptake in renal osteodystrophy

Energy Technology Data Exchange (ETDEWEB)

de Graaf, P.; Schicht, I.M.; de Graeff, J.; te Velde, J.; Kleiverda, K.; Pauwels, E.K.J.

1982-04-01

Bone radiotracer uptake in renal osteodystrophy was investigated in 35 dialysis patients by correlating the results of quantitative bone scintigraphy with those of biochemical and bone morphometric studies. There were highly significant correlations (P < 0.001) between the total skeletal activity and the biochemical (iPTH and alkaline phosphatase), and histologic parameters of hyperparathyroidism. These clinical results strongly suggest that increased bone turnover i.e. hyperparathyroidism, rather than osteomalacia is the major cause of increased skeletal uptake in renal osteodystrophy.

Mineral and Skeletal Homeostasis Influence the Manner of Bone Loss in Metabolic Osteoporosis due to Calcium-Deprived Diet in Different Sites of Rat Vertebra and Femur

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Marzia Ferretti

2015-01-01

Full Text Available Rats fed calcium-deprived diet develop osteoporosis due to enhanced bone resorption, secondary to parathyroid overactivity resulting from nutritional hypocalcemia. Therefore, rats provide a good experimental animal model for studying bone modelling alterations during biochemical osteoporosis. Three-month-old Sprague-Dawley male rats were divided into 4 groups: (1 baseline, (2 normal diet for 4 weeks, (3 calcium-deprived diet for 4 weeks, and (4 calcium-deprived diet for 4 weeks and concomitant administration of PTH (1-34 40 µg/Kg/day. Histomorphometrical analyses were made on cortical and trabecular bone of lumbar vertebral body as well as of mid-diaphysis and distal metaphysis of femur. In all rats fed calcium-deprived diet, despite the reduction of trabecular number (due to the maintenance of mineral homeostasis, an intense activity of bone deposition occurs on the surface of the few remaining trabeculae (in answering to mechanical stresses and, consequently, to maintain the skeletal homeostasis. Different responses were detected in different sites of cortical bone, depending on their main function in answering mineral or skeletal homeostasis. This study represents the starting point for work-in-progress researches, with the aim of defining in detail timing and manners of evolution and recovery of biochemical osteoporosis.

Skeletal lesions from inhaled plutonium in beagles

International Nuclear Information System (INIS)

Dagle, G.E.; Park, J.F.; Weller, R.E.; Ragan, H.A.; McClanahan, B.J.; Fisher, D.R.

1984-10-01

The report briefly reviews the skeletal effects observed in ongoing lifespan studies in beagle dogs at 13, 10, and 7 years, respectively, after inhalation exposure to 239 Pu oxide and nitrate or 238 Pu oxide. Plutonium nitrate was chosen to represent soluble material more readily translocated to bone and other tissues than the oxide. Bone lesions related to plutonium exposure were observed only in dogs exposed to 238 Pu oxide and 239 Pu nitrate. The skeleton accumulated approximately 2% ( 239 Pu oxide), 45% ( 238 Pu oxide) or 50% ( 239 Pu nitrate) of the final body burdens at 13, 10, and 7 years, respectively, after exposure. 11 references, 2 figures

Comparative analysis of the skeletal changes in tetrapods after brief influence of microgravity.

Science.gov (United States)

Nikitin, V B; Gulimova, V I; Ilyin, E A; Asadchikov, V E; Buzmakov, A V; Okshtein, I L; Saveliev, S V

2007-07-01

Experiments involving lower tetrapods demonstrate that the degree of skeletal demineralization in spaceflights is related to the type of environmental behaviour of the animal. Probably the sensing of support reaction decreases the negative effect of spaceflight upon the bone tissue.

Skeletal and muscular status in juveniles with GFD treated clinical and newly diagnosed atypical celiac disease--preliminary data.

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Płudowski, Paweł; Karczmarewicz, Elzbieta; Socha, Jerzy; Matusik, Halina; Syczewska, Małgorzata; Lorenc, Roman S

2007-01-01

Undiagnosed and untreated celiac disease (CD) constitutes an increasing skeletal health problem due to its association with low bone density and fractures. Examinations of skeletal status in children using dual-energy X-ray absorptiometry (DXA) are prone to size-related misinterpretation. In contrary, the analysis of muscle-bone relationship seems to limit a possibility of misdiagnosis because skeletal status is evaluated from the functional perspective. The study was aimed to assess skeletal status of children suffering from CD with the use of muscle-bone functional algorithm. The study group comprised 29 celiac patients (13.7yr+/-2.9) on gluten-free diet (GFD), and 24 newly diagnosed atypical celiac patients, including subgroup with normal height (n=14; 12.6yr+/-3.9) and subgroup with short stature (n=10; 12.2yr+/-2.9). Muscular and skeletal status was evaluated by DXA (DPX-L, GE). Anthropometry, total body bone mineral density (TBBMD, g/cm(2)). and total body bone mineral content (TBBMC, g) as well as lean body mass (LBM, g) were evaluated. Muscle-bone interactions were estimated using TBBMC/LBM ratio. Previously established references for healthy controls were used for the calculation of Z-scores (age-matched) and SD-scores (height-matched). GFD treated celiacs and atypical celiacs with normal body height had TBBMD, TBBMC, LBM, and TBBMC/LBM ratio Z-scores and SD-scores within normal range for healthy controls. In contrary, atypical celiacs with short stature had significantly lower Z-scores for TBBMD (-2.3+/-0.4), TBBMC (-2.1+/-0.3), LBM (-1.4+/-0.3). and TBBMC/LBM ratio (-2.3+/-0.6) when compared to respective values observed in GFD treated celiacs (pnormal height (pvalues observed in GFD treated celiacs (+0.04+/-0.2; pnormal height (-0.4+/-0.2; pvalues of DXA assessed indicators of bone and muscle status as well as normal muscle-bone interactions. Untreated atypical celiacs may present a broad spectrum of heterogeneous abnormalities from normal to markedly

Bone Metabolism after Bariatric Surgery

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Yu, Elaine W.

2014-01-01

Bariatric surgery is a popular and effective treatment for severe obesity, but may have negative effects on the skeleton. This review summarizes changes in bone density and bone metabolism from animal and clinical studies of bariatric surgery, with specific attention to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and sleeve gastrectomy (SG). Skeletal imaging artifacts from obesity and weight loss are also considered. Despite challenges in bone density imaging, the preponderance of evidence suggests that bariatric surgery procedures have negative skeletal effects that persist beyond the first year of surgery, and that these effects vary by surgical type. The long-term clinical implications and current clinical recommendations are presented. Further study is required to determine mechanisms of bone loss after bariatric surgery. Although early studies focused on calcium/vitamin D metabolism and mechanical unloading of the skeleton, it seems likely that surgically-induced changes in the hormonal and metabolic profile may be responsible for the skeletal phenotypes observed after bariatric surgery. PMID:24677277

Evaluation of the utility of 99m Tc-MDP bone scintigraphy versus MIBG scintigraphy and cross-sectional imaging for staging patients with neuroblastoma.

Science.gov (United States)

Gauguet, Jean-Marc; Pace-Emerson, Tamara; Grant, Frederick D; Shusterman, Suzanne; DuBois, Steven G; Frazier, A Lindsay; Voss, Stephan D

2017-11-01

Accurate staging of neuroblastoma requires multiple imaging examinations. The purpose of this study was to determine the relative contribution of 99m Tc-methylene diphosphonate (MDP) bone scintigraphy (bone scan) versus metaiodobenzylguanidine scintigraphy (MIBG scan) for accurate staging of neuroblastoma. A medical record search by the identified patients with neuroblastoma from 1993 to 2012 who underwent both MIBG and bone scan for disease staging. Cross-sectional imaging was used to corroborate the scintigraphy results. Clinical records were used to correlate imaging findings with clinical staging and patient management. One hundred thirty-two patients underwent both MIBG and bone scan for diagnosis. All stage 1 (n = 12), 2 (n = 8), and 4S (n = 4) patients had a normal bone scan with no skeletal MIBG uptake. Six of 30 stage 3 patients had false (+) bone scans. In the 78 stage 4 patients, 58/78 (74%) were both skeletal MIBG(+)/bone scan (+). In 56 of the 58 cases, skeletal involvement detected with MIBG was equal to or greater than that detected by bone scan. Only 3/78 had (-) skeletal MIBG uptake and (+) bone scans; all 3 had other sites of metastatic disease. Five of 78 had (+) skeletal MIBG with a (-) bone scan, while 12/78 had no skeletal involvement by either MIBG or bone scan. In no case did a positive bone scan alone determine a stage 4 designation. In the staging of neuroblastoma, 99m Tc-MDP bone scintigraphy does not identify unique sites of disease that affect disease stage or clinical management, and in the majority of cases bone scans can be omitted from the routine neuroblastoma staging algorithm. © 2017 Wiley Periodicals, Inc.

Autophagy: a new player in skeletal maintenance?

Science.gov (United States)

Hocking, Lynne J; Whitehouse, Caroline; Helfrich, Miep H

2012-07-01

Imbalances between bone resorption and formation lie at the root of disorders such as osteoporosis, Paget's disease of bone (PDB), and osteopetrosis. Recently, genetic and functional studies have implicated proteins involved in autophagic protein degradation as important mediators of bone cell function in normal physiology and in pathology. Autophagy is the conserved process whereby aggregated proteins, intracellular pathogens, and damaged organelles are degraded and recycled. This process is important both for normal cellular quality control and in response to environmental or internal stressors, particularly in terminally-differentiated cells. Autophagic structures can also act as hubs for the spatial organization of recycling and synthetic process in secretory cells. Alterations to autophagy (reduction, hyperactivation, or impairment) are associated with a number of disorders, including neurodegenerative diseases and cancers, and are now being implicated in maintenance of skeletal homoeostasis. Here, we introduce the topic of autophagy, describe the new findings that are starting to emerge from the bone field, and consider the therapeutic potential of modifying this pathway for the treatment of age-related bone disorders. Copyright © 2012 American Society for Bone and Mineral Research.

Radiography and bone scintigraphy in multiple myeloma: a comparative analysis

International Nuclear Information System (INIS)

Ludwig, H.; Kumpan, W.; Sinzinger, H.

1982-01-01

The sensitivity of radionuclide imaging for detecting skeletal lesions was compared with that of radiography by evaluating 573 different anatomical sites in 41 patients with multiple myeloma. Radiography revealed a significantly greater number of myeloma-related bone lesions than did radionuclide imaging. Of the 179 myeloma-related bone lesions detected when both techniques were applied, 163 were seen by radiography and 82 by radionuclide imaging. Ninety-seven lesions were detected by radiography alone and 16 lesions seen by scintiscanning only, yielding a sensitivity of 91% for the former and of 46% for the latter technique. Radionuclide imaging proved superior to radiography only occasionally in the rib cage, and rarely in other anatomical sites. These findings suggest that radiography is the method of first choice in obtaining a skeletal survey in patients with multiple myeloma. In cases with continued pain, unexplained by standard radiography, the skeletal survey should be supplemented by tomography and radionuclide imaging. (author)

SERUM YKL-40 IS ASSOCIATED WITH BONE DISEASE IN MULTIPLE MYELOMA

DEFF Research Database (Denmark)

Mylin, Anne Kjærsgaard; Abildgaard, Niels; Johansen, Julia S.

2007-01-01

 Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix, in angiogen...... Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix...... and followed for up to 30 months. Skeletal related events (SRE) were registered and subdivided in vertebral fractures and osteolytic events including non-vertebral fractures. Results. 57% of the patients had a S-YKL-40 elevated above the upper limit in an age specific 90 per cent reference range for healthy...... adults. Patients with elevated S-YKL-40 had a higher total X-ray score (p=0.005) and higher levels of S-CTX-MMP (p=0.003), U-PYD (p=0.004) and U-DPD (p=0.002), while U-NTX-1 and the markers of bone formation did not differ from the levels seen in patients with normal S-YKL-40. During follow-up 21...

Computed tomography guidance for skeletal biopsy

International Nuclear Information System (INIS)

Frager, D.H.; Goldman, M.J.; Elkin, C.M.; Cynamon, J.; Leeds, N.E.; Seimon, L.P.; Habermann, E.T.; Schreiber, K.; Freeman, L.M.

1987-01-01

Computed tomographic (CT) guided biopsy and abscess drainage of multiple organ systems have been well described. Reports of spinal and skeletal applications have been less common. This study describes the use of CT guidance in the biopsy of various skeletal lesions in 46 patients. Forty-one patients had skinny needle aspirations (18 or 22 gauge) and 23 patients had trephine core biopsies. Sites of the lesions included: thoracic spine - 15 patients, lumbosacral spine - 17 patients, bony pelvis - 6 patients, rib - 2 patients, and long bones - 6 patients. Fast scanners capable of rapid image reconstruction have overcome many constraints. With CT guidance, the physician who performs the procedure receives virtually no ionizing radiation. The exact location of the needle tip is accurately visualized in relation to the lesion being biopsied and to the vital organs. (orig.)

Hindlimb Skeletal Muscle Function and Skeletal Quality and Strength in +/G610C Mice With and Without Weight-Bearing Exercise.

Science.gov (United States)

Jeong, Youngjae; Carleton, Stephanie M; Gentry, Bettina A; Yao, Xiaomei; Ferreira, J Andries; Salamango, Daniel J; Weis, MaryAnn; Oestreich, Arin K; Williams, Ashlee M; McCray, Marcus G; Eyre, David R; Brown, Marybeth; Wang, Yong; Phillips, Charlotte L

2015-10-01

Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue disorder associated with reduced bone mineral density and skeletal fragility. Bone is inherently mechanosensitive, with bone strength being proportional to muscle mass and strength. Physically active healthy children accrue more bone than inactive children. Children with type I OI exhibit decreased exercise capacity and muscle strength compared with healthy peers. It is unknown whether this muscle weakness reflects decreased physical activity or a muscle pathology. In this study, we used heterozygous G610C OI model mice (+/G610C), which model both the genotype and phenotype of a large Amish OI kindred, to evaluate hindlimb muscle function and physical activity levels before evaluating the ability of +/G610C mice to undergo a treadmill exercise regimen. We found +/G610C mice hindlimb muscles do not exhibit compromised muscle function, and their activity levels were not reduced relative to wild-type mice. The +/G610C mice were also able to complete an 8-week treadmill regimen. Biomechanical integrity of control and exercised wild-type and +/G610C femora were analyzed by torsional loading to failure. The greatest skeletal gains in response to exercise were observed in stiffness and the shear modulus of elasticity with alterations in collagen content. Analysis of tibial cortical bone by Raman spectroscopy demonstrated similar crystallinity and mineral/matrix ratios regardless of sex, exercise, and genotype. Together, these findings demonstrate +/G610C OI mice have equivalent muscle function, activity levels, and ability to complete a weight-bearing exercise regimen as wild-type mice. The +/G610C mice exhibited increased femoral stiffness and decreased hydroxyproline with exercise, whereas other biomechanical parameters remain unaffected, suggesting a more rigorous exercise regimen or another exercise modality may be required to improve bone quality of OI mice. © 2015 American Society for Bone

DNA Profiling Success Rates from Degraded Skeletal Remains in Guatemala.

Science.gov (United States)

Johnston, Emma; Stephenson, Mishel

2016-07-01

No data are available regarding the success of DNA Short Tandem Repeat (STR) profiling from degraded skeletal remains in Guatemala. Therefore, DNA profiling success rates relating to 2595 skeletons from eleven cases at the Forensic Anthropology Foundation of Guatemala (FAFG) are presented. The typical postmortem interval was 30 years. DNA was extracted from bone powder and amplified using Identifiler and Minifler. DNA profiling success rates differed between cases, ranging from 50.8% to 7.0%, the overall success rate for samples was 36.3%. The best DNA profiling success rates were obtained from femur (36.2%) and tooth (33.7%) samples. DNA profiles were significantly better from lower body bones than upper body bones (p = <0.0001). Bone samples from males gave significantly better profiles than samples from females (p = <0.0001). These results are believed to be related to bone density. The findings are important for designing forensic DNA sampling strategies in future victim recovery investigations. © 2016 American Academy of Forensic Sciences.

The Skeletal Biology of Hibernating Woodchucks (Marmota monax)

Science.gov (United States)

Doherty, Alison H.

Long periods of inactivity in most mammals lead to significant bone loss that may not be completely recovered during an individual's lifetime regardless of future activity. Extended bouts of inactivity are the norm for hibernating mammals. It remains largely unknown, however, how these animals avoid adversely affecting bone, their quality, and ultimately survival given the challenges posed to their skeletons by inactivity and nutritional deprivation during hibernation. The primary goal of this project was to identify the physiological mechanisms regulating bone density, area and strength during extended periods of annual inactivity in hibernating woodchucks (Marmota monax). The overall hypothesis that bone integrity is unaffected by several months of inactivity during hibernation in woodchucks was tested across multiple levels of biological function. To gain a holistic assessment of seasonal bone integrity, the locomotor behavior and estimated stresses acting on woodchuck bones were investigated in conjunction with computed tomography scans and three-point bending tests to determine bone density, geometry, and mechanical properties of the long bones throughout the year. In addition, serum protein expression was examined to ascertain bone resorption and formation processes indicative of overall annual skeletal health. It was determined that woodchucks avoid significant changes in gait preference, but experience a decrease in bending stresses acting on distal limb bones following hibernation. Computed tomography scans indicated that bone mass, distribution, and trabecular structure are maintained in these animals throughout the year. Surprisingly, cortical density increased significantly posthibernation. Furthermore, three-point bending tests revealed that although less stiff, woodchuck femora were just as tough during the hibernation season, unlike brittle bones associated with osteoporosis. Finally, bone serum markers suggested a net maintenance of bone resorption

Osteopoikilosis: A Sign Mimicking Skeletal Metastases in a Cancer Patient

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Hamid Nasrolahi

2011-01-01

Full Text Available Osteopoikilosis is a rare benign osteosclerotic bone disorder that may be misdiagnosed as skeletal metastases. Here we describe a case of coincidental breast cancer and osteopoikilosis mimicking skeletal metastases. A 41-year-old woman underwent right modified radical mastectomy in April 2007. Twenty-eight months after initial treatment,the patient complained of bilateral knee and foot pain. Plain X-rays of the feet and knees showed multiple well-defined osteosclerotic lesions. According to the radiographic appearance, the most likely differential diagnoses included skeletal metastases from breast cancer and osteopoikilosis. A whole-body bone scintigraphy showed no increase in uptake by the sclerotic lesions, and serum lactic dehydrogenase, carcinoembryonic antigen, alkaline phosphatase and cancer antigen 15-3 were not elevated. We therefore diagnosed the patient’s skeletal lesions as osteopoikilosis. This case and ourliterature review suggest that the radiographic appearance of osteopoikilosis may mimic or mask skeletal metastases, potentially leading to misdiagnosis in patients with cancer.

Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

Science.gov (United States)

Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

2016-09-01

Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious

Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

Directory of Open Access Journals (Sweden)

Chiaming Fan

2011-01-01

Full Text Available The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX, the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

A role for PERK in the mechanism underlying fluoride-induced bone turnover

International Nuclear Information System (INIS)

Sun, Fei; Li, Xining; Yang, Chen; Lv, Peng; Li, Guangsheng; Xu, Hui

2014-01-01

While it has been well-documented that excessive fluoride exposure caused the skeletal disease and osteoblasts played a critical role in the advanced skeletal fluorosis, the underlying mechanism that mediated these effects remain poorly understood. The present study was undertaken to examine the effect of fluoride on bone of rats and MC3T3-E1 cells in vitro. Herein we found pathological features of high bone turnover in fluoride-treated rats, which was supported by an increase of osteogenic and osteoclastogenic genes expression in different stages of fluoride exposure. The skeletal toxicity of fluoride was accompanied by activation of endoplasmic reticulum (ER) stress and subsequent unfolded protein response (UPR). A novel finding of this study was that expression of PKR-like endoplasmic reticulum kinase (PERK) was the same trend with receptor activator for nuclear factor-κ B ligand (RANKL), and NF-E2 p45-related factor 2 (Nrf2) was the same trend with Runt-related transcription factor 2 (Runx2) in bones of rats exposed to varied fluoride condition. Based on these data, we hypothesized that up-regulation of PERK probably played a role in mediating bone turnover induced by fluoride. Action of fluoride on MC3T3-E1 cells differentiation was demonstrated through analysis of alkaline phosphatase (ALP) activity and mineralized nodules formation. Meantime, an increase of binding immunoglobulin protein (BiP) expression indicated the active ER stress in cells exposed to various dose of fluoride. Blocking PERK expression using siRNA showed the obvious decrease of osteogenic and osteoclastogenic factors expression in MC3T3-E1 cells exposed to certain dose of fluoride that could positively stimulate osteoblastic viability. In conclusion these findings underscore the importance of PERK in modulating fluoride induced bone formation and bone resorption. Understanding the link between PERK and bone turnover could probe into the mechanism underlying different bone lesion of

Bone development

DEFF Research Database (Denmark)

Tatara, M.R.; Tygesen, Malin Plumhoff; Sawa-Wojtanowicz, B.

2007-01-01

The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram.......01). Furthermore, AKG administration induced significantly higher bone mineral density of the cortical bone by 7.1% (P

Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.

Directory of Open Access Journals (Sweden)

Teruyo Oishi

Full Text Available Heterotopic ossification (HO is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+ and PDGFRα(+ cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+ cells and PDGFRα(+ cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+ cells formed bone-like tissue and showed successful engraftment, while CD56(+ cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+ cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+ cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+ cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+ cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+ cells. Our results suggest that PDGFRα(+ cells may be the major source of HO and that the newly identified mi

Treatment with N- and C-Terminal Peptides of Parathyroid Hormone-Related Protein Partly Compensate the Skeletal Abnormalities in IGF-I Deficient Mice

Science.gov (United States)

Portal-Núñez, Sergio; Murillo-Cuesta, Silvia; Lozano, Daniel; Cediel, Rafael; Esbrit, Pedro

2014-01-01

Insulin-like growth factor-I (IGF-I) deficiency causes growth delay, and IGF-I has been shown to partially mediate bone anabolism by parathyroid hormone (PTH). PTH-related protein (PTHrP) is abundant in bone, and has osteogenic features by poorly defined mechanisms. We here examined the capacity of PTHrP (1–36) and PTHrP (107–111) (osteostatin) to reverse the skeletal alterations associated with IGF-I deficiency. Igf1-null mice and their wild type littermates were treated with each PTHrP peptide (80 µg/Kg/every other day/2 weeks; 2 males and 4 females for each genotype) or saline vehicle (3 males and 3 females for each genotype). We found that treatment with either PTHrP peptide ameliorated trabecular structure in the femur in both genotypes. However, these peptides were ineffective in normalizing the altered cortical structure at this bone site in Igf1-null mice. An aberrant gene expression of factors associated with osteoblast differentiation and function, namely runx2, osteoprotegerin/receptor activator of NF-κB ligand ratio, Wnt3a , cyclin D1, connexin 43, catalase and Gadd45, as well as in osteocyte sclerostin, was found in the long bones of Igf1-null mice. These mice also displayed a lower amount of trabecular osteoblasts and osteoclasts in the tibial metaphysis than those in wild type mice. These alterations in Igf1-null mice were only partially corrected by each PTHrP peptide treatment. The skeletal expression of Igf2, Igf1 receptor and Irs2 was increased in Igf1-null mice, and this compensatory profile was further improved by treatment with each PTHrP peptide related to ERK1/2 and FoxM1 activation. In vitro, PTHrP (1–36) and osteostatin were effective in promoting bone marrow stromal cell mineralization in normal mice but not in IGF-I-deficient mice. Collectively, these findings indicate that PTHrP (1–36) and osteostatin can exert several osteogenic actions even in the absence of IGF-I in the mouse bone. PMID:24503961

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.

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population

OpenAIRE

Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

2015-01-01

Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and l...

Influence of fall related factors and bone strength on fracture risk in the frail elderly.

Science.gov (United States)

Sambrook, P N; Cameron, I D; Chen, J S; Cumming, R G; Lord, S R; March, L M; Schwarz, J; Seibel, M J; Simpson, J M

2007-05-01

When subjects are selected on the basis of fall risk alone, therapies for osteoporosis have not been effective. In a prospective study of elderly subjects at high risk of falls, we investigated the influence of bone strength and fall risk on fracture. At baseline we assessed calcaneal bone ultrasound attenuation (BUA) as well as quantitative measures of fall risk in 2005 subjects in residential care. Incident falls and fractures were recorded (median follow-up 705 days). A total of 6646 fall events and 375 low trauma fracture events occurred. The fall rate was 214 per 100 person years and the fracture rate 12.1 per 100 person years. 82% of the fractures could be attributed to falls. Although fracture rates increased with decreasing BUA (incidence rate ratio 1.94 for lowest vs. highest BUA tertile, pfalls also affected fracture incidence. Subjects who fell frequently (>3.15 falls/per person year) were 3.35 times more likely to suffer a fracture than those who did not fall. Some fall risk factors such as balance were associated with the lowest fracture risk lowest in the worst performing group. Multivariate analysis revealed higher fall rate, history of previous fracture, lower BUA, lower body weight, cognitive impairment and better balance as significant independent risk factors for fracture. In the frail elderly, both skeletal fragility and fall risk including the frequency of exposure to falls are important determinants of fracture risk.

Embryonic stem cells in bone tissue engineering

NARCIS (Netherlands)

Both, Sanne Karijn

2008-01-01

Due to increased life expectancy of humans the number of patients with age related skeletal compliciations has increased. These patients but also patients suffering from complications due to trauma or disease often need surgical interventions in which additional bone is required for optimal

MicroCT-Based Skeletal Models for Use in Tomographic Voxel Phantoms for Radiological Protection

International Nuclear Information System (INIS)

Bolch, Wesley

2010-01-01

The University of Florida (UF) proposes to develop two high-resolution image-based skeletal dosimetry models for direct use by ICRP Committee 2's Task Group on Dose Calculation in their forthcoming Reference Voxel Male (RVM) and Reference Voxel Female (RVF) whole-body dosimetry phantoms. These two phantoms are CT-based, and thus do not have the image resolution to delineate and perform radiation transport modeling of the individual marrow cavities and bone trabeculae throughout their skeletal structures. Furthermore, new and innovative 3D microimaging techniques will now be required for the skeletal tissues following Committee 2's revision of the target tissues of relevance for radiogenic bone cancer induction. This target tissue had been defined in ICRP Publication 30 as a 10-(micro)m cell layer on all bone surfaces of trabecular and cortical bone. The revised target tissue is now a 50-(micro)m layer within the marrow cavities of trabecular bone only and is exclusive of the marrow adipocytes. Clearly, this new definition requires the use of 3D microimages of the trabecular architecture not available from past 2D optical studies of the adult skeleton. With our recent acquisition of two relatively young cadavers (males of age 18-years and 40-years), we will develop a series of reference skeletal models that can be directly applied to (1) the new ICRP reference voxel man and female phantoms developed for the ICRP, and (2) pediatric phantoms developed to target the ICRP reference children. Dosimetry data to be developed will include absorbed fractions for internal beta and alpha-particle sources, as well as photon and neutron fluence-to-dose response functions for direct use in external dosimetry studies of the ICRP reference workers and members of the general public

MicroCT-Based Skeletal Models for Use in Tomographic Voxel Phantoms for Radiological Protection

Energy Technology Data Exchange (ETDEWEB)

Bolch, Wesley [Univ. of Florida, Gainesville, FL (United States)

2010-03-30

The University of Florida (UF) proposes to develop two high-resolution image-based skeletal dosimetry models for direct use by ICRP Committee 2’s Task Group on Dose Calculation in their forthcoming Reference Voxel Male (RVM) and Reference Voxel Female (RVF) whole-body dosimetry phantoms. These two phantoms are CT-based, and thus do not have the image resolution to delineate and perform radiation transport modeling of the individual marrow cavities and bone trabeculae throughout their skeletal structures. Furthermore, new and innovative 3D microimaging techniques will now be required for the skeletal tissues following Committee 2’s revision of the target tissues of relevance for radiogenic bone cancer induction. This target tissue had been defined in ICRP Publication 30 as a 10-μm cell layer on all bone surfaces of trabecular and cortical bone. The revised target tissue is now a 50-μm layer within the marrow cavities of trabecular bone only and is exclusive of the marrow adipocytes. Clearly, this new definition requires the use of 3D microimages of the trabecular architecture not available from past 2D optical studies of the adult skeleton. With our recent acquisition of two relatively young cadavers (males of age 18-years and 40-years), we will develop a series of reference skeletal models that can be directly applied to (1) the new ICRP reference voxel man and female phantoms developed for the ICRP, and (2) pediatric phantoms developed to target the ICRP reference children. Dosimetry data to be developed will include absorbed fractions for internal beta and alpha-particle sources, as well as photon and neutron fluence-to-dose response functions for direct use in external dosimetry studies of the ICRP reference workers and members of the general public

Skeletal malformations in fetuses with Meckel syndrome

DEFF Research Database (Denmark)

Kjaer, K W; Fischer Hansen, B; Keeling, J W

1999-01-01

one foot was normal. Malformations of the cranial base (the basilar part of the occipital bone or the postsphenoid bone) occurred in five cases, and the vertebral bodies in the lumbar region of the spine were malformed (cleft) in three cases. It is proposed that a skeletal analysis be included...

Cellular and molecular prerequisites for bone tissue engineering

NARCIS (Netherlands)

Siddappa, Ramakrishnaiah

2007-01-01

Recent advances in medicine and other biological disciplines have considerably enhanced the life expectancy of human and consequently, resulting in age related health problems including skeletal complications. In addition, bone substitute to regenerate fractures resulting from trauma, congenital and

Women Build Long Bones With Less Cortical Mass Relative to Body Size and Bone Size Compared With Men.

Science.gov (United States)

Jepsen, Karl J; Bigelow, Erin M R; Schlecht, Stephen H

2015-08-01

The twofold greater lifetime risk of fracturing a bone for white women compared with white men and black women has been attributed in part to differences in how the skeletal system accumulates bone mass during growth. On average, women build more slender long bones with less cortical area compared with men. Although slender bones are known to have a naturally lower cortical area compared with wider bones, it remains unclear whether the relatively lower cortical area of women is consistent with their increased slenderness or is reduced beyond that expected for the sex-specific differences in bone size and body size. Whether this sexual dimorphism is consistent with ethnic background and is recapitulated in the widely used mouse model also remains unclear. We asked (1) do black women build bones with reduced cortical area compared with black men; (2) do white women build bones with reduced cortical area compared with white men; and (3) do female mice build bones with reduced cortical area compared with male mice? Bone strength and cross-sectional morphology of adult human and mouse bone were calculated from quantitative CT images of the femoral midshaft. The data were tested for normality and regression analyses were used to test for differences in cortical area between men and women after adjusting for body size and bone size by general linear model (GLM). Linear regression analysis showed that the femurs of black women had 11% lower cortical area compared with those of black men after adjusting for body size and bone size (women: mean=357.7 mm2; 95% confidence interval [CI], 347.9-367.5 mm2; men: mean=400.1 mm2; 95% CI, 391.5-408.7 mm2; effect size=1.2; pbone size (women: mean=350.1 mm2; 95% CI, 340.4-359.8 mm2; men: mean=394.3 mm2; 95% CI, 386.5-402.1 mm2; effect size=1.3; pbone size (female: mean=0.73 mm2; 95% CI, 0.71-0.74 mm2; male: mean=0.70 mm2; 95% CI, 0.68-0.71 mm2; effect size=0.74; p=0.04, GLM). Female femurs are not simply a more slender version of male

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

DEFF Research Database (Denmark)

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

2016-01-01

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

Evaluation of the efficiency of FDG PET/CT in detection and characterization of skeletal metastases

Directory of Open Access Journals (Sweden)

Ahmed Wafaie

2014-03-01

Conclusion: Fused PET/CT was highly efficient in evaluation of skeletal metastases with superior performance in: detection of early bone marrow infiltration not apparent on CT, resolution of metabolic activity before definite signs of complete healing on CT, detection of missed sclerotic metastases on PET due to their relatively low metabolic activity, detection of intra and extra osseous recurrence and differentiation of benign from malignant bone lesions.

Zoledronic Acid improves clinical outcomes when administered before onset of bone pain in patients with prostate cancer.

Science.gov (United States)

Saad, Fred; Eastham, James

2010-11-01

To evaluate, in an exploratory analysis, the effect of zoledronic acid (ZOL) on skeletal-related event (SRE) incidence as determined by the bone pain levels at study entry. Bone metastases can undermine skeletal integrity long before the onset of symptoms. Treating patients before symptom onset might be more effective in preventing SREs and improving patients' quality of life. ZOL has shown significant reductions in SREs and pain compared with placebo in patients with bone metastases from advanced prostate cancer in a randomized placebo-controlled trial. Patients from a placebo-controlled, Phase III trial of men with castration-resistant prostate cancer, randomized to receive ZOL 4 mg (n = 214) or placebo (n = 208) for ≤ 24 months, were stratified by pain or no pain at baseline. Bone pain was assessed at baseline, week 3, and week 6 and at 6-week intervals thereafter. The primary endpoint was the proportion of patients with ≥ 1 SRE. ZOL significantly reduced the mean pain scores compared with placebo at 3, 9, 21, and 24 months (P ≤ .03 for each point) and reduced the annual incidence of SREs. Among patients without baseline pain, ZOL decreased the percentage of patients with ≥ 1 SRE by 39% and reduced the annual incidence of SREs by 49% compared with placebo. ZOL delayed the onset of bone pain in those patients without pain at baseline compared with placebo. ZOL reduced bone pain and SREs compared with placebo in patients with bone metastases from castration-resistant prostate cancer, irrespective of the baseline pain status, and appeared more efficacious when initiated before the onset of pain. Copyright © 2010 Elsevier Inc. All rights reserved.

Desferrioxamine-induced long bone changes in thalassaemic patients - Radiographic features, prevalence and relations with growth

Energy Technology Data Exchange (ETDEWEB)

Chan, Y.L.; Li, C.K.; Pang, L.M.; Chik, K.W

2000-08-01

AIM: To study the radiographic findings of desferrioxamine-induced bone dysplasia, its prevalence and relation to growth in thalassaemic patients. MATERIALS AND METHODS: A cross-sectional study was performed in 35 thalassaemic patients on a hypertransfusion scheme and chelation therapy at a dose not exceeding 50 mg/kg/day. Radiographs of the left hand taken for bone age assessment in consecutive patients over the past 12 months were evaluated for signs of desferrioxamine-induced bone dysplasia. The findings were correlated with data on growth, chelation and body iron content. RESULTS: Twelve of 35 patients had evidence of desferrioxamine-induced long bone dysplasia. There was no significant difference in the groups with and without radiographic evidence of bone dysplasia with respect to the height percentile at time of initiation of therapy, height percentile at time of radiography, skeletal age delay, age at starting chelation, chelation dose and duration, units of blood transfused, average chelation dose, and serum ferritin levels at time of radiography. Both groups showed a reduced percentile growth with a significantly greater reduction (P = 0.03) in the patients with dysplastic change. CONCLUSION: Desferrioxamine-induced bone dysplasia is associated with height reduction and can be seen in patients receiving desferrioxamine chelation therapy at doses of less than 50 mg/kg/day. Awareness of the diagnosis is of importance as reduction of the desferrioxamine dose may improve bone growth. Chan, Y. L. (2000)

Skeletal sarcoidosis; Skelettsarkoidose

Energy Technology Data Exchange (ETDEWEB)

Freyschmidt, J. [Klinikum Bremen-Mitte, Beratungsstelle und Referenzzentrum fuer Osteoradiologie, Bremen (Germany); Freyschmidt, P. [Dermatologische Gemeinschaftspraxis, Schwalmstadt (Germany)

2016-10-15

Presentation of the etiology, pathology, clinical course, radiology and differential diagnostics of skeletal sarcoidosis. Noncaseating epithelioid cell granulomas can trigger solitary, multiple or disseminated osteolysis, reactive osteosclerosis and/or granulomatous synovitis. The incidence of sarcoidosis is 10-12 per 100,000 inhabitants per year. Skeletal involvement is approximately 14 %. Skeletal involvement occurs almost exclusively in the stage of lymph node and pulmonary manifestation. Most cases of skeletal involvement are clinically asymptomatic. In the case of synovial involvement, unspecific joint complaints (arthralgia) or less commonly arthritis can occur. Typical skin alterations can be diagnostically significant. Punch out lesions osteolysis, coarse destruction and osteosclerosis can occur, which are best visualized with projection radiography and/or computed tomography. Pure bone marrow foci without interaction with the bone can only be detected with magnetic resonance imaging (MRI) and more recently with positron emission tomography (PET), mostly as incidental findings. There is a predeliction for the hand and trunk skeleton. Skeletal tuberculosis, metastases, multiple myeloma, Langerhans cell histiocytosis and sarcoid-like reactions in solid tumors must be differentiated. The key factors for correct diagnosis are thorax radiography, thorax CT and dermatological manifestations. (orig.) [German] Darstellung von Aetiologie, Pathologie, Klinik, Radiologie und Differenzialdiagnose der Skelettsarkoidose. Nichtverkaesende Epitheloidzellgranulome koennen solitaere, multiple oder disseminierte Osteolysen, reaktive Osteosklerosen und/oder eine granulomatoese Synovialitis ausloesen. Inzidenz der Sarkoidose: 10-12/100.000 Einwohner/Jahr. Skelettbeteiligung ca. 14 %. Skelettbeteiligungen kommen fast ausschliesslich im Stadium einer Lymphknoten- und pulmonalen Manifestation vor. Die meisten Skelettbeteiligungen verlaufen klinisch stumm. Bei synovialer

IGF-1 signaling mediated cell-specific skeletal mechano-transduction.

Science.gov (United States)

Tian, Faming; Wang, Yongmei; Bikle, Daniel D

2018-02-01

Mechanical loading preserves bone mass and stimulates bone formation, whereas skeletal unloading leads to bone loss. In addition to osteocytes, which are considered the primary sensor of mechanical load, osteoblasts, and bone specific mesenchymal stem cells also are involved. The skeletal response to mechanical signals is a complex process regulated by multiple signaling pathways including that of insulin-like growth factor-1 (IGF-1). Conditional osteocyte deletion of IGF-1 ablates the osteogenic response to mechanical loading. Similarly, osteocyte IGF-1 receptor (IGF-1R) expression is necessary for reloading-induced periosteal bone formation. Transgenic overexpression of IGF-1 in osteoblasts results in enhanced responsiveness to in vivo mechanical loading in mice, a response which is eliminated by osteoblastic conditional disruption of IGF-1 in vivo. Bone marrow derived stem cells (BMSC) from unloaded bone fail to respond to IGF-1 in vitro. IGF-1R is required for the transduction of a mechanical stimulus to downstream effectors, transduction which is lost when the IGF-1R is deleted. Although the molecular mechanisms are not yet fully elucidated, the IGF signaling pathway and its interactions with potentially interlinked signaling cascades involving integrins, the estrogen receptor, and wnt/β-catenin play an important role in regulating adaptive response of cancer bone cells to mechanical stimuli. In this review, we discuss recent advances investigating how IGF-1 and other interlinked molecules and signaling pathways regulate skeletal mechano-transduction involving different bone cells, providing an overview of the IGF-1 signaling mediated cell-specific response to mechanical stimuli. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:576-583, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

[Impact of thyroid diseases on bone].

Science.gov (United States)

Tsourdi, E; Lademann, F; Siggelkow, H

2018-05-09

Thyroid hormones are key regulators of skeletal development in childhood and bone homeostasis in adulthood, and thyroid diseases have been associated with increased osteoporotic fractures. Hypothyroidism in children leads to an impaired skeletal maturation and mineralization, but an adequate and timely substitution with thyroid hormones stimulates bone growth. Conversely, hyperthyroidism at a young age accelerates skeletal development, but may also cause short stature because of a premature fusion of the growth plates. Hypothyroidism in adults causes an increase in the duration of the remodeling cycle and, thus, leads to low bone turnover and enhanced mineralization, but an association with a higher fracture risk is less well established. In adults, a surplus of thyroid hormones enhances bone turnover, mostly due to an increased bone resorption driven by osteoclasts. Thus, hyperthyroidism is a well-recognized cause of high-bone turnover secondary osteoporosis, resulting in an increased susceptibility to fragility fractures. Subclinical hyperthyroidism, especially resulting from endogenous disease, also has an adverse effect on bone mineral density and is associated with fractures. In most patients with overt or subclinical hyperthyroidism restoration of the euthyroid status reverses bone loss. In postmenopausal women who receive thyroid-stimulating hormone suppression therapy because of thyroid cancer, antiresorptive treatments may be indicated. Overall, extensive data support the importance of a euthyroid status for bone mineral accrual and growth in childhood as well as maintenance of bone health in adulthood.

CT findings in skeletal cystic echinococcosis

Energy Technology Data Exchange (ETDEWEB)

Tuezuen, M.; Hekimoglu, B. [Social Security Hospital, Ankara (Turkey). Dept. of Radiology

2002-09-01

Purpose: To evaluate the CT findings of skeletal cystic echinococcosis. Material and Methods: CT findings of 7 patients with pathologically confirmed skeletal cystic echinococcosis were evaluated. Results: There were 4 men and 3 women, aged 36-75 years. Hydatid cysts were located in the spine (n=2), a rib (n=3), the pelvis and a vertebra (n=1), the pelvis and the left femur (n=1). The size of the lesions varied from 1 cm to 15 cm. CT showed well defined, single or multiple cystic lesions with no contrast enhancement, no calcification, no daughter cysts, and no germinal membrane detachment. The cystic lesion had a honeycomb appearance in 2 cases, there was pathologic fracture in 2 cases, bone expansion in 5 cases, cortical thinning in 6 cases, cortical destruction in 6 cases, bone sclerosis in 1 case, and soft tissue extension in 6 cases. Conclusion: Preoperative differential diagnosis of skeletal cystic lesions should include cystic echinococcosis, especially in endemic areas, since this diagnosis may easily be missed unless kept in mind.

Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma

International Nuclear Information System (INIS)

Boutry, Nathalie; Dutouquet, Bastien; Cotten, Anne; Leleu, Xavier; Vieillard, Marie-Helene; Duhamel, Alain

2013-01-01

To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. (orig.)

Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma

Energy Technology Data Exchange (ETDEWEB)

Boutry, Nathalie [University Hospital of Jeanne de Flandre and University of Lille 2, Departments of Pediatric and Musculoskeletal Imaging, Lille (France); University Hospital of Jeanne de Flandre and University of Lille 2, Department of Pediatric Imaging, Lille (France); Hopital Jeanne de Flandre, Service de Radiopediatrie, Lille (France); Dutouquet, Bastien; Cotten, Anne [University Hospital of Roger Salengro and University of Lille 2, Department of Musculoskeletal Imaging, Lille (France); Leleu, Xavier [University Hospital of Claude Huriez and University of Lille 2, Clinical Hematology Department, Lille (France); Vieillard, Marie-Helene [University Hospital of Roger Salengro and University of Lille 2, Rheumatology Department, Lille (France); Duhamel, Alain [University of Lille 2, Department of Medical Statistics, Lille (France)

2013-08-15

To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. (orig.)

Fibrous dysplasia mimicking bone metastasis on both bone scintigraphy and 18F FDG PET CT: Diagnostic dilemma in a patient with breast cancer

International Nuclear Information System (INIS)

KC, Sud Hir Suman; Sharma, Punit; Singh, Har Man Deep; Bal, Chand Rasekhar; Kumar, Rake Sh

2012-01-01

Bone is the most common distant site to which breast cancer metastasizes. Commonly used imaging modalities for imaging bone metastasis are bone scintigraphy, plain radiography, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Although bone scintigraphy gas high sensitivity for detecting bone metastasis, its specificity is low. This is because of the fact that bone scintigraphy images secondary changes in bone rather than just tumor cells 18 F fluorodeoxyglucose ( 18 F FDG) PET CT, on the other hand, directly images the tumor cells' glucose metabolism. Unfortunately, similar to bone scintigraphy, benign bone conditions can also show increased 18 F FDG uptake on PET CT, and PET positive asymptomatic fibrous dysplasia can be misinterpreted as a metastasis. Fibrous dysplasia of bone has wide skeletal distribution, with variability of 18 F FDG uptake and CT appearance. It is therefore important to recognize the characteristics of this skeletal dysplasia, to allow differentiation from skeletal metastasis. Bone lesions with 18 F FDG uptake need to be carefully interpreted when evaluating patients with known malignancy. In doubtful cases, fibrous dysplasia should be given as a differential diagnosis and histopathological diagnosis may be warranted, as highlighted in the present case

Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australasian Menopause Society and the Clinical Oncology Society of Australia.

Science.gov (United States)

Grossmann, Mathis; Ramchand, Sabashini; Milat, Frances; Vincent, Amanda; Lim, Elgene; Kotowicz, Mark A; Hicks, Jill; Teede, Helena

2018-05-09

To formulate clinical consensus recommendations on bone health assessment and management of women with oestrogen receptor-positive early breast cancer receiving endocrine therapy. Representatives appointed by relevant Australian Medical Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing five key questions. Women receiving adjuvant aromatase inhibitors and the subset of premenopausal woman on tamoxifen have accelerated bone loss and increased fracture risk. Both bisphosphonates and denosumab prevent bone loss, additionally denosumab has proven anti-fracture benefit. Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density (BMD) measurement, with monitoring based on risk factors. Weight-bearing exercise, vitamin D and calcium sufficiency is recommended routinely. Antiresorptive treatment should be considered in women with prevalent or incident clinical or morphometric fractures, a T-score (or Z-scores in women <50 years) of <-2.0 at any site, or if annual bone loss is ≥5%, considering baseline BMD and other fracture risk factors. Duration of antiresorptive treatment can be individualised based on absolute fracture risk. Relative to their skeletal benefits, risks of adverse events with antiresorptive treatments are low. Skeletal health should be considered in the decision-making process regarding choice and duration of endocrine therapy. Before and during endocrine therapy, skeletal health should be assessed regularly, optimised by nonpharmacological intervention and where indicated antiresorptive treatment, in an individualised, multidisciplinary approach. Clinical trials are needed to better delineate long-term fracture risks of adjuvant endocrine therapy, and to determine the efficacy of interventions designed to minimise these risks. This article is protected by copyright. All rights reserved. This

Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats.

Science.gov (United States)

Folwarczna, Joanna; Pytlik, Maria; Zych, Maria; Cegieła, Urszula; Kaczmarczyk-Sedlak, Ilona; Nowińska, Barbara; Sliwiński, Leszek

2013-10-01

Caffeine, a methylxanthine present in coffee, has been postulated to be responsible for an increased risk of osteoporosis in coffee drinkers; however, the data are inconsistent. The aim of the present study was to investigate the effects of a moderate dose of caffeine on the skeletal system of rats with normal and decreased estrogen level (developing osteoporosis due to estrogen deficiency). The experiments were carried out on mature nonovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving caffeine once daily, 20 mg/kg p.o., for 4 wk. Serum bone turnover markers, bone mass, mass of bone mineral, calcium and phosphorus content, histomorphometric parameters, and bone mechanical properties were examined. Caffeine favorably affected the skeletal system of ovariectomized rats, slightly inhibiting the development of bone changes induced by estrogen deficiency (increasing bone mineralization, and improving the strength and structure of cancellous bone). Moreover, it favorably affected mechanical properties of compact bone. There were no significant effects of caffeine in rats with normal estrogen levels. In conclusion, results of the present study indicate that low-to-moderate caffeine intake may exert some beneficial effects on the skeletal system of mature organisms. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discordant Findings of Skeletal Metastasis Between Tc99m MDP Bone Scans and F18 FDG PET/CT Imaging for Advanced Breast and Lung Cancers—Two Case Reports and Literature Review

Directory of Open Access Journals (Sweden)

Yu-Wen Chen

2007-12-01

Full Text Available Traditionally, Tc99m methyl diphosphate (MDP bone scintigraphy provides high-sensitivity detection of skeletal metastasis from breast and lung cancers in regular follow-up. Fluorodeoxyglucose (FDG positron emission tomography/computed tomography (PET/CT, based on the glucose metabolism of malignant cells, plays a role in describing rumor growth, proliferation of neoplasm and the extent of metastasis. In general, concordant findings of skeletal metastasis are seen on both types of image, especially in cases of breast and lung cancer. However, there were extremely discordant findings of skeletal metastasis between bone scans and F18 FDG PET/CT imaging in two cases among 300 consecutive F18 FDG PET/CT follow-up exams of patients with malignancies, during the past year, in our center. Both cases, one of breast cancer and one of lung cancer, had negative bone scintigraphic findings, but a diffusely high grade of F18 FDG avid marrow infiltration in the axial spine, leading to the diagnosis of stage IV disease in both cases. Owing to variant genetic aberrance of malignance, F18 FDG PET/CT reveals direct evidence of diffuse, rapid neoplasm metabolism in the bone marrow of the spine, but not of secondary osteoblastic reactions in vivo. F18 FDG PET/CT should always be employed in the follow-up of patients with malignancies.

Assessment of mandibular growth by skeletal scintigraphy

International Nuclear Information System (INIS)

Kaban, L.B.; Cisneros, G.J.; Heyman, S.; Treves, S.

1982-01-01

Accurate assessment of facial skeletal growth remains a major problem in craniomaxillofacial surgery. Current methods include: (1) comparisons of chronologic age with growth histories of the patient and the family, (2) hand-wrist radiographs compared with a standard, and (3) serial cephalometric radiographs. Uptake of technetium-99m methylene diphosphonate into bone is a reflection of current metabolic activity and blood flow. Therefore, scintigraphy with this radiopharmaceutical might serve as a good method of assessing skeletal growth. Thirty-four patients, ranging in age from 15 months to 22 years, who were undergoing skeletal scintigrams for acute pathologic conditions of the extremities, were used to develop standards of uptake based on age and skeletal maturation. The results indicate that skeletal scintigraphy may be useful in evaluation of mandibular growth

Impact of radiation history, gender and age on bone quality in sites for orthodontic skeletal anchorage device placement.

Science.gov (United States)

Konermann, A; Appel, T; Wenghoefer, M; Sirokay, S; Dirk, C; Jäger, A; Götz, W

2015-05-01

Stability of orthodontic miniscrew implants is prerequisite to their success and durability in orthodontic treatment. As investigations revealed a positive correlation of miniscrew stability to periimplant bone quality, it has been the aim of this study to analyze the bone structure of resection preparations of human mandibles histologically by investigating the samples according to age, gender and exposure to radiotherapy. Inflammation- and tumor-free alveolar bone sections from human mandibles (n = 31) with previously diagnosed carcinoma, chronic osteomyelitis or cysts were analyzed histomorphologically and histomorphometrically as to the dimension of trabeculae in cancellous areas. Group A investigated the impact of a history of radiation therapy, group B of gender and group C contrasted biopsies from individuals aging under 60 or over 60 years. Statistics were performed using the Kruskal-Wallis-test. Radiation, gender and age did not significantly influence bone density. The mean bone density averaged 40.7 ± 15.0% of spongiosa for the total collective with a median age of 58.4 years ± 14.7 years. Our findings provide new information on bone quality, thus contributing to a more precise evaluation of the parameters affecting and those not affecting miniscrew implant stability. On the basis of these results, the formulation of clinical guidelines for risk assessment of therapeutic approaches in patients prior to insertion of orthodontic skeletal anchorage devices seems to be conceivable. Copyright © 2014 Elsevier GmbH. All rights reserved.

Growth of limb muscle is dependent on skeletal-derived Indian hedgehog

OpenAIRE

Bren-Mattison, Yvette; Hausburg, Melissa; Olwin, Bradley B.

2011-01-01

During embryogenesis, muscle and bone develop in close temporal and spatial proximity. We show that Indian Hedgehog, a bone-derived signaling molecule, participates in growth of skeletal muscle. In Ihh−/− embryos, skeletal muscle development appears abnormal at embryonic day 14.5 and at later ages through embryonic day 20.5, dramatic losses of hindlimb muscle occur. To further examine the role of Ihh in myogenesis, we manipulated Ihh expression in the developing chick hindlimb. Reduction of I...

Bone marrow immunoscintigraphy using technetium-99m anti-granulocyte antibody in multiple myeloma

International Nuclear Information System (INIS)

Sohn, Sang-Kyun; Kim, Dong-Hwan; Park, So-Hyang; Ahn, Byeong-Cheol; Lee, Sang-Woo; Chun, Kyung-Ah; Kim, Jung-Gyun; Lee, Kyu Bo; Lee, Jaetae; Song, Hong-Suk

2002-01-01

Conventional skeletal radiography and bone scan have certain limitations in the initial evaluation of bone and bone marrow lesions in multiple myeloma (MM). In this study we investigated the value of bone marrow immunoscintigraphy (BMIS) using anti-granulocyte monoclonal antibody (AGA) for the diagnosis of bone involvement of MM, in comparison with bone scan and skeletal radiography. Whole-body BMIS using technetium-99m-labelled AGA was performed in 22 MM patients (15 male, 7 female) and the imaging findings compared with those of skeletal radiography and 99m Tc-methylene diphosphonate bone scan. The findings of bone marrow aspiration and serum biochemical findings were also compared with BMIS findings. Abnormal findings of BMIS were defined as presence of a focal photon defect in the axial skeleton or expansion of peripheral bone marrow. A total of 124 focal lesions were detected in 19 subjects (86%) by skeletal radiography, bone scan or BMIS. BMIS detected 92 lesions (74%) in 19 subjects, whereas skeletal radiography detected 58 focal lesions (47%) in 14 and bone scan 40 lesions (32%) in 11. Fifty-one (41%) of the 124 lesions were only seen on BMIS. Spine and pelvic lesions were better visualised by BMIS, whereas skull lesions were better seen with skeletal radiography, and bone scan detected more lesions in the ribs. Marrow expansion was noted in 15 subjects (68%) on BMIS, and its grade correlated with marrow cellularity and myeloma cell percentage in bone marrow aspirates (P=0.0055 and P=0.0541, respectively). BMIS revealed abnormal lesions in one of three stage II patients and 17 out of 19 stage III patients. The number of lesions of the thoracolumbar vertebrae on BMIS was correlated with cellularity (P=0.0393), but not with myeloma cell percentage (P=0.1262). These findings suggest that the results of BMIS with 99m Tc-labelled AGA correlate with clinical stage, and thus reflect the functional status of bone marrow in MM patients. BMIS might be useful for the

The effects of bone marrow aspirate, bone graft, and collagen composites on fixation of titanium implants

DEFF Research Database (Denmark)

Babiker, Hassan; Ding, Ming; Sandri, Monica

2012-01-01

Replacement of extensive local bone loss especially in revision joint arthroplasty and spine fusion is a significant clinical challenge. Allograft and autograft have been considered as gold standards for bone replacement. However, there are several disadvantages such as donor site pain, bacterial...... contamination, and non union as well as the potential risk of disease transmission. Hydroxyapatite and collagen composites (HA/Collagen) have the potential in mimicking and replacing skeletal bones. This study attempted to determine the effects of newly developed HA/Collagen-composites with and without bone...... marrow aspirate (BMA) on enhancement of bone implant fixation. Method: Titanium alloy implants were inserted into bilateral femoral condyles of eight skeletally mature sheep, four implants per sheep. The implant had a circumferential gap of 2 mm. The gap was filled with: HA/Collagen; HA...

Bone scintigraphy in lesions of the skull

International Nuclear Information System (INIS)

Fischer, M.; Wasilewski, A.; Deitmer, T.

1982-01-01

The value of 3-phase-scintigraphy in bone lesions of the skull with a new seeking agent 99mTc-2,3-dicarboxypropane-1,1-diphosphonic acid (DPD) is studied. A high soft tissue-bone-ratio of DPD is emphasized. For this reason DPD is used for bone scintigraphy of the skull, because the mass of soft tissue in relation to bone is high and a higher clearance improves the interpretation of the images of the first two phases. An increased tracer uptake is found for skeletal neoplasms (malignant and benign lesions) and for acute osteomyelitis. By contrast, the chronic inflammatory bone lesions showed normal tracer uptake. This new bone seeking agent allows to localize and differentiate tumorous or acute inflammatory lesions and chronic inflammatory bone lesions of the skull

Osteogenesis and angiogenesis: The potential for engineering bone

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JM Kanczler

2008-05-01

Full Text Available The repair of large bone defects remains a major clinical orthopaedic challenge. Bone is a highly vascularised tissue reliant on the close spatial and temporal connection between blood vessels and bone cells to maintain skeletal integrity. Angiogenesis thus plays a pivotal role in skeletal development and bone fracture repair. Current procedures to repair bone defects and to provide structural and mechanical support include the use of grafts (autologous, allogeneic or implants (polymeric or metallic. These approaches face significant limitations due to insufficient supply, potential disease transmission, rejection, cost and the inability to integrate with the surrounding host tissue.The engineering of bone tissue offers new therapeutic strategies to aid musculoskeletal healing. Various scaffold constructs have been employed in the development of tissue-engineered bone; however, an active blood vessel network is an essential pre-requisite for these to survive and integrate with existing host tissue. Combination therapies of stem cells and polymeric growth factor release scaffolds tailored to promote angiogenesis and osteogenesis are under evaluation and development actively to stimulate bone regeneration. An understanding of the cellular and molecular interactions of blood vessels and bone cells will enhance and aid the successful development of future vascularised bone scaffold constructs, enabling survival and integration of bioengineered bone with the host tissue. The role of angiogenic and osteogenic factors in the adaptive response and interaction of osteoblasts and endothelial cells during the multi step process of bone development and repair will be highlighted in this review, with consideration of how some of these key mechanisms can be combined with new developments in tissue engineering to enable repair and growth of skeletal fractures. Elucidation of the processes of angiogenesis, osteogenesis and tissue engineering strategies offer

Unusual skeletal metastases from myxoid liposarcoma only detectable by MR imaging

International Nuclear Information System (INIS)

Ishii, T.; Ueda, T.; Myoui, A.; Tamai, N.; Hosono, N.; Yoshikawa, H.

2003-01-01

We present two cases of skeletal metastases from myxoid liposarcoma, occurring several years after treatment of the primary tumors in the lower limb. The present two case reports have unusual radiological features only detectable by MR imaging and not by plain radiographs or bone scans. From the present two cases, we found that a negative plain radiograph of the spine or a negative bone scan could not exclude skeletal metastases from myxoid liposarcoma, and MRI was a more sensitive screening procedure for their detection, especially in T1-weighted images. Unusual radiological features of skeletal metastases from myxoid liposarcoma are not well documented and only a few cases have been previously reported. Our aim is to document two more patients exhibiting the unusual radiological features of skeletal metastases from myxoid liposarcoma to improve their early detection and management. (orig.)

As solid as a rock-comparison of CE- and MPS-based analyses of the petrosal bone as a source of DNA for forensic identification of challenging cranial bones.

Science.gov (United States)

Kulstein, Galina; Hadrys, Thorsten; Wiegand, Peter

2018-01-01

Short tandem repeat (STR) typing from skeletal remains can be a difficult task. Dependent on the environmental conditions of the provenance of the bones, DNA can be degraded and STR typing inhibited. Generally, dense and compact bones are known to preserve DNA better. Several studies already proved that femora and teeth have high DNA typing success rates. Unfortunately, these elements are not present in all cases involving skeletal remains. Processing partial or singular skeletal elements, it is favorable to select bone areas where DNA preservation is comparably higher. Especially, cranial bones are often accidentally discovered during criminal investigations. The cranial bone is composed of multiple parts. In this examination, we evaluated the potential of the petrous bone for human identification of skeletal remains in forensic case work. Material from different sections of eight unknown cranial bones and-where available-additionally other skeletal elements, collected at the DNA department of the Institute of Legal Medicine in Ulm, Germany, from 2010 to 2017, were processed with an optimized DNA extraction and STR typing strategy. The results highlight that STR typing from the petrous bones leads to reportable profiles in all individuals, even in cases where the analysis of the parietal bone failed. Moreover, the comparison of capillary electrophorese (CE) typing to massively parallel sequencing (MPS) analysis shows that MPS has the potential to analyze degraded human remains and is even capable to provide additional information about phenotype and ancestry of unknown individuals.

Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production.

Science.gov (United States)

Courtland, Hayden-William; Sun, Hui; Beth-On, Mordechay; Wu, Yingjie; Elis, Sebastien; Rosen, Clifford J; Yakar, Shoshana

2011-04-01

Deficiencies in either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) are associated with reductions in bone size during growth in humans and animal models. Liver-specific IGF-1-deficient (LID) mice, which have 75% reductions in serum IGF-1, were created previously to separate the effects of endocrine (serum) IGF-1 from autocrine/paracrine IGF-1. However, LID mice also have two- to threefold increases in GH, and this may contribute to the observed pubertal skeletal phenotype. To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age. Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice. Reductions in both Tt.Ar and Le were proportional after treatment with pegvisomant. On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice, indicating that antagonizing GH action, either directly (through GH receptor signaling inhibition) or indirectly (through further reductions in serum/tissue IGF-1 levels), results in disproportionate reductions in the amount of cortical bone formed. This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased), suggesting that compensatory increases of GH in states of IGF-1 deficiency (LID mice) act to protect against a severe inhibition of bone modeling during growth, which otherwise would result in bones that are too weak for normal and/or extreme loading conditions. Copyright © 2011 American Society for

Membranous lipodystrophy: skeletal findings on CT and MRI

Energy Technology Data Exchange (ETDEWEB)

Nwawka, O.K.; Schneider, Robert; Mintz, Douglas N. [Hospital for Special Surgery, Department of Radiology and Imaging, New York, NY (United States); Bansal, Manjula [Hospital for Special Surgery, Department of Pathology and Laboratory Medicine, New York, NY (United States); Lane, Joseph [Hospital for Special Surgery, Department of Orthopedic Surgery, New York, NY (United States)

2014-10-15

Membranous lipodystrophy, also known as Nasu-Hakola disease, is a rare hereditary condition with manifestations in the nervous and skeletal systems. The radiographic appearance of skeletal lesions has been well described in the literature. However, CT and MRI findings of lesions in the bone have not been documented to date. This report describes the radiographic, CT, MRI, and histopathologic skeletal findings in a case of membranous lipodystrophy. With corroborative pathologic findings, a diagnosis of membranous lipodystrophy on imaging allows for appropriate clinical management of disease manifestations. (orig.)

Relative Skeletal Muscle Mass Is Associated with Development of Metabolic Syndrome

Directory of Open Access Journals (Sweden)

Byung Sam Park

2013-12-01

Full Text Available BackgroundVisceral adiposity is related to insulin resistance. Skeletal muscle plays a central role in insulin-mediated glucose disposal; however, little is known about the association between muscle mass and metabolic syndrome (MS. This study is to clarify the clinical role of skeletal muscle mass in development of MS.MethodsA total of 1,042 subjects were enrolled. Subjects with prior MS and chronic diseases were excluded. After 24 months, development of MS was assessed using NCEP-ATP III criteria. Skeletal muscle mass (SMM; kg, body fat mass (BFM; kg, and visceral fat area (VFA; cm2 were obtained from bioelectrical analysis. Then, the following values were calculated as follows: percent of SMM (SMM%; %: SMM (kg/weight (kg, skeletal muscle index (SMI; kg/m2: SMM (kg/height (m2, skeletal muscle to body fat ratio (MFR: SMM (kg/BFM (kg, and skeletal muscle to visceral fat ratio (SVR; kg/cm2: SMM (kg/VFA (cm2.ResultsAmong 838 subjects, 88 (10.5% were newly diagnosed with MS. Development of MS increased according to increasing quintiles of BMI, SMM, VFA, and SMI, but was negatively associated with SMM%, MFR, and SVR. VFA was positively associated with high waist circumference (WC, high blood pressure (BP, dysglycemia, and high triglyceride (TG. In contrast, MFR was negatively associated with high WC, high BP, dysglycemia, and high TG. SVR was negatively associated with all components of MS.ConclusionRelative SMM ratio to body composition, rather than absolute mass, may play a critical role in development of MS and could be used as a strong predictor.

Concepts on the pathogenesis of adolescent idiopathic scoliosis. Bone growth and mass, vertebral column, spinal cord, brain, skull, extra-spinal left-right skeletal length asymmetries, disproportions and molecular pathogenesis.

Science.gov (United States)

Burwell, R Geoffrey; Dangerfield, Peter H; Freeman, Brian J C

2008-01-01

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). Encouraging advances thought to be related to AIS pathogenesis have recently been made in several fields including anthropometry of bone growth, bone mass, spinal growth modulation, extra-spinal left-right skeletal length asymmetries and disproportions, magnetic resonance imaging of vertebral column, spinal cord, brain, skull, and molecular pathogenesis. These advances are leading to the evaluation of new treatments including attempts at minimally invasive surgery on the spine and peri-apical ribs. Several concepts of AIS are outlined indicating their clinical applications but not their research potential. The concepts, by derivation morphological, molecular and mathematical, are addressed in 15 sections: 1) initiating and progressive factors; 2) relative anterior spinal overgrowth; 3) dorsal shear forces that create axial rotational instability; 4) rotational preconstraint; 5) uncoupled, or asynchronous, spinal neuro-osseous growth; 6) brain, nervous system and skull; 7) a novel neuro-osseous escalator concept based on a putative abnormality of two normal polarized processes namely, a) increasing skeletal dimensions, and b) the CNS body schema - both contained within a neuro-osseous timing of maturation (NOTOM) concept; 8) transverse plane pelvic rotation, skeletal asymmetries and developmental theory; 9) thoraco-spinal concept; 10) origin in contracture at the hips; 11) osteopenia; 12) melatonin deficiency; 13) systemic melatonin-signaling pathway dysfunction; 14) platelet calmodulin dysfunction; and 15) biomechanical spinal growth modulation. From these concepts, a collective model for AIS pathogenesis is formulated. The central concept of this model includes the body schema of the neural systems, widely-studied in adults, that control normal posture and coordinated movements with frames of reference in the posterior parietal cortex. The escalator concept

Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation

Science.gov (United States)

Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

2016-01-01

Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclastspecific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β–induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss. PMID:26108893

Altered elementary calcium release events and enhanced calcium release by thymol in rat skeletal muscle.

Science.gov (United States)

Szentesi, Péter; Szappanos, Henrietta; Szegedi, Csaba; Gönczi, Monika; Jona, István; Cseri, Julianna; Kovács, László; Csernoch, László

2004-03-01

The effects of thymol on steps of excitation-contraction coupling were studied on fast-twitch muscles of rodents. Thymol was found to increase the depolarization-induced release of calcium from the sarcoplasmic reticulum, which could not be attributed to a decreased calcium-dependent inactivation of calcium release channels/ryanodine receptors or altered intramembrane charge movement, but rather to a more efficient coupling of depolarization to channel opening. Thymol increased ryanodine binding to heavy sarcoplasmic reticulum vesicles, with a half-activating concentration of 144 micro M and a Hill coefficient of 1.89, and the open probability of the isolated and reconstituted ryanodine receptors, from 0.09 +/- 0.03 to 0.22 +/- 0.04 at 30 micro M. At higher concentrations the drug induced long-lasting open events on a full conducting state. Elementary calcium release events imaged using laser scanning confocal microscopy in the line-scan mode were reduced in size, 0.92 +/- 0.01 vs. 0.70 +/- 0.01, but increased in duration, 56 +/- 1 vs. 79 +/- 1 ms, by 30 micro M thymol, with an increase in the relative proportion of lone embers. Higher concentrations favored long events, resembling embers in control, with duration often exceeding 500 ms. These findings provide direct experimental evidence that the opening of a single release channel will generate an ember, rather than a spark, in mammalian skeletal muscle.

The Japanese Medakafish (Oryzias latipes) as Animal Model for Space-related Bone Research

Science.gov (United States)

Renn, J.; Schaedel, M.; Elmasri, H.; Wagner, T.; Goerlich, R.; Furutani-Seiki, M.; Kondoh, H.; Schartl, M.; Winkler, C.

Long-term space flight leads to bone loss due to reduced mechanical load. Animal models are needed to support the analysis of the underlying mechanisms at the molecular and cellular level that are presently largely unclear. For this, small laboratory fish offer many experimental advantages as in vivo models to study disease related processes. They produce large numbers of completely transparent embryos, are easy to keep under laboratory and space conditions and have relatively compact genomes. We are using the Japanese Medaka to characterize the genetic networks regulating bone formation and to study bone formation and remodeling under microgravity. We showed that despite the large evolutionary distance many known factors regulating bone formation are conserved between fish and humans. This includes osteoprotegerin (opg), a key regulator of bone resorption that is altered at the transcriptional level by simulated microgravity in mammals in vitro (Kanematsu et al., Bone 30, 2002). To monitor, how opg is regulated by altered gravity in vivo in fish and how fish react to microgravity, we isolated the Medaka opg regulatory region and produced transgenic fish that carry the green fluorescent protein reporter under the control of the Medaka opg promoter. This model will be useful to monitor gravity-induced changes at the molecular level in vivo. Fish also provide the opportunity to identify novel genes involved in bone formation by using large-scale mutagenesis screens. We have characterized several lines of mutant fish subjected to ENU mutagenesis that show morphological defects in the formation of the bone precursor cell compartment of the axial skeleton, the sclerotome. Using this genetic approach, the identification of the mutated genes is expected to reveal novel components of the genetic cascades that regulate bone formation. In an attempt to identify genes specifically expressed in the sclerotome in Medaka, we identified and characterized dmrt2, a gene that so far

The influence of lifestyle, menstrual function and oral contraceptive use on bone mass and size in female military cadets

Directory of Open Access Journals (Sweden)

Tendy Susan

2007-08-01

Full Text Available Abstract Purpose To determine the influence of menstrual irregularity, oral contraceptive use and other factors on bone mineral density (BMD and bone size at different skeletal sites in 135 college-aged fit women. Methods Menstrual history, oral contraceptive use, exercise history, and nutritional factors including calcium, caffeine, and alcohol intake as well as tobacco use were determined by written survey. Height, weight and fitness levels were measured. Spine and hip BMD were measured by dual x-ray absorptiometry (DXA, calcaneus BMD by peripheral DXA, and tibial bone mineral content (BMC and size by peripheral Quantitative Computed Tomography (pQCT. Results The mean age was 18.4 ± 0.8 years. Weight and prior exercise were positively related to BMD at most skeletal sites and to tibial bone size. Milk intake was positively related to calcaneal BMD, tibial BMC and cortical thickness. Fracture history was an important predictor of spine, hip and heel BMD. Women who had ≥ 10 menstrual cycles in the year prior to BMD measurement had higher BMD at all sites as well as a greater tibial mineral content and cortical thickness than women who had oligomenorrhea/amenorrhea (≤ 9 cycles in the prior year; all p p p = 0.04, smaller tibial periosteal circumference and lower tibial mineral content (p Conclusion In a population of fit, college-aged women, OC use and oligomenorrhea were associated with reduced BMD and bone size. Weight, as well as prior exercise and milk intake was positively related to bone density and size at some skeletal sites. Understanding these relationships would help improve skeletal health in young women.

Clinical application of skeletal scintigraphy and quantitative computed tomography (QCT) to osteoarthritis of the knee

International Nuclear Information System (INIS)

Mori, Muneshige

1989-01-01

Skeletal scintigraphy and QCT were performed to determine changes of subchondral bone tissues in osteoarthritis of the knee and findings were compared with plain X-ray findings, knee pain and femoro-tibial angle. Results on blood pool study were especially related to pain. Results in delayed study using single photon emission computed tomography revealed hign uptake on the medial side of the femur and tibia parallel to plain X-ray and pain. The QCT value was slightly decreased as osteoarthritic changes progressed without a significant change. In addition, delayed study in cases with previous surgical intervention by high tibial osteotomy revealed a lower uptake on the medial side of the femur and tibia. When skeletal scintigraphy accurately reflects blood flow through the subchondral bone tissues and is closely related to morbidity and pain, this modality is valuable in analysis of signs and symptoms as well as postoperative outcome. (author)

Bone scintigraphy in renal osteodystrophy

International Nuclear Information System (INIS)

de Graaf, P.; Schicht, I.M.; Pauwels, E.K.J.; te Velde, J.; de Graeff, J.

1978-01-01

Bone scintigraphy with Tc-99m HEDP was performed in 30 patients on maintenance hemodialysis, and the results of quantitative analysis were compared wth those of a normal group. To permit this comparison, elevated background activity due to the absence of renal radiotracer excretion was reduced by hemodialysis to levels found in the normals. Histologic proof of renal osteodystrophy had been obtained in all patients. the incidence of radiographic abnormalities was 46%, whereas abnormal scans were found in 25 patients (83%); skeletal lesions were also more pronounced and detected earlier. However, even when the scans appeared normal, the quantitative analysis showed increased skeletal activity in all patients. The total skeletal activity proved to be a good index of the severity of renal osteodystrophy and appeared dependent on both osteomalacia and hyperparathyroidism. These findings show that bone scintigraphy is a sensitive method to detect skeletal involvement in renal osteodystrophy

Use of dual-energy computed tomography to measure skeletal-wide marrow composition and cancellous bone mineral density.

Science.gov (United States)

Arentsen, Luke; Hansen, Karen E; Yagi, Masashi; Takahashi, Yutaka; Shanley, Ryan; McArthur, Angela; Bolan, Patrick; Magome, Taiki; Yee, Douglas; Froelich, Jerry; Hui, Susanta K

2017-07-01

Temporal and spatial variations in bone marrow adipose tissue (MAT) can be indicative of several pathologies and confound current methods of assessing immediate changes in bone mineral remodeling. We present a novel dual-energy computed tomography (DECT) method to monitor MAT and marrow-corrected volumetric BMD (mcvBMD) throughout the body. Twenty-three cancellous skeletal sites in 20 adult female cadavers aged 40-80 years old were measured using DECT (80 and 140 kVp). vBMD was simultaneous recorded using QCT. MAT was further sampled using MRI. Thirteen lumbar vertebrae were then excised from the MRI-imaged donors and examined by microCT. After MAT correction throughout the skeleton, significant differences (p < 0.05) were found between QCT-derived vBMD and DECT-derived mcvBMD results. McvBMD was highly heterogeneous with a maximum at the posterior skull and minimum in the proximal humerus (574 and 0.7 mg/cc, respectively). BV/TV and BMC have a nearly significant correlation with mcvBMD (r = 0.545, p = 0.057 and r = 0.539, p = 0.061, respectively). MAT assessed by DECT showed a significant correlation with MRI MAT results (r = 0.881, p < 0.0001). Both DECT- and MRI-derived MAT had a significant influence on uncorrected vBMD (r = -0.86 and r = -0.818, p ≤ 0.0001, respectively). Conversely, mcvBMD had no correlation with DECT- or MRI-derived MAT (r = 0.261 and r = 0.067). DECT can be used to assess MAT while simultaneously collecting mcvBMD values at each skeletal site. MAT is heterogeneous throughout the skeleton, highly variable, and should be accounted for in longitudinal mcvBMD studies. McvBMD accurately reflects the calcified tissue in cancellous bone.

Relationship of natural incidence and radiosensitivity for bone cancer in dogs

International Nuclear Information System (INIS)

Taylor, G.N.; Lloyd, R.D.; Miller, S.C.; Jee, W.S.S.

1997-01-01

A comparison of the risk coefficients for 239 Pu- or 226 Ra-induced bone cancer in two canine breeds, one with a relatively low (beagle) and the other with a very high (St. Bernard) natural incidence, indicated only slightly higher risk in the giant breed. The differences in risk for skeletal malignancy in 239 Pu and 226 Ra dogs were nonsignificant (p > 0.05). Likewise, the values of the 239 Pu: 226 Ra open-quotes toxicity ratiosclose quotes for these respective breeds, using bone cancer as the endpoint, were not significantly different at the 0.05 level. The anatomical distribution of the radiation-induced bone tumors tended to be a function of both the bone mass and the skeletal distribution of the radio nuclide, not the site of predilection for naturally occurring bone neoplasia. Although the etiology of the higher natural incidence of bone cancer in the St. Bernard was not determined, several possible factors, including a higher osteoblastic activity level in the St. Bernards, are presented. These data suggest that making extrapolations of radiation-induced bone cancer risk from animals to humans is valid. 26 refs., 5 tabs

Cerebellar medulloblastoma presenting with skeletal metastasis

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Barai Sukanta

2004-04-01

Full Text Available Medulloblastomas are highly malignant brain tumours, but only rarely produce skeletal metastases. No case of medulloblastoma has been documented to have produced skeletal metastases prior to craniotomy or shunt surgery. A 21-year-old male presented with pain in the hip and lower back with difficulty in walking of 3 months′ duration. Signs of cerebellar dysfunction were present hence a diagnosis of cerebellar neoplasm or skeletal tuberculosis with cerebellar abscess formation was considered. MRI of brain revealed a lesion in the cerebellum suggestive of medulloblastoma. Bone scan revealed multiple sites of skeletal metastases excluding the lumbar vertebrae. MRI of lumbar spine and hip revealed metastases to all lumbar vertebrae and both hips. Computed tomography-guided biopsy was obtained from the L3 vertebra, which revealed metastatic deposits from medulloblastoma. Cerebrospinal fluid cytology showed the presence of medulloblastoma cells. A final diagnosis of cerebellar medulloblastoma with skeletal metastases was made. He underwent craniotomy and histopathology confirmed medulloblastoma.

Estrogens and Androgens in Skeletal Physiology and Pathophysiology.

Science.gov (United States)

Almeida, Maria; Laurent, Michaël R; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A; Bouillon, Roger; Vanderschueren, Dirk; Manolagas, Stavros C

2017-01-01

Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. Copyright © 2017 the American Physiological Society.

Methods and application of bone densitometry in clinical diagnosis

International Nuclear Information System (INIS)

Wahner, H.W.; Riggs, B.L.

1986-01-01

With the awareness of osteoporosis as a major health problem for an aging population, there is great interest in early recognition and treatment of abnormal bone loss. Effective prevention of bone loss has to occur prior to the occurrence of irreparable damage. Standard radiographic procedures are not sensitive enough for the task. Therefore, a number of alternative procedures to estimate bone loss have been developed over the years, ranging from efforts to quantitate information obtained from radiographic images to sophisticated procedures such as neutron activation analysis or procedures based on the Compton scatter phenomenon. Only two procedures, photon absorptiometry and computed tomography (CT), have emerged as applicable for routine clinical use. In photon absorptiometry the entire bone mineral (cortical and trabecular bone) of a specific skeletal site is measured. CT allows measuring of bone mineral of trabecular or cortical bone alone. Normally, bone mass reaches a maximum in the third decade and then continuously declines. This age-related bone loss is greater in women in whom an accelerated rate of loss occurs at the menopause. When bone density reaches a critical fracture threshold, skeletal fractures occur (spine, hip, and distal long bones). The age at which this critical fracture threshold is reached depends on the maximal bone mass achieved in early adulthood and the rate of loss with increasing age. With the exception of NaF, present-day therapeutic efforts only retard or prevent bone loss but do not significantly add bone mineral to the skeleton. Recognition of high-risk groups and early treatment are therefore required. 79 references

Comparison of skeletal scintigraphy and radiology for showing the osseous manifestations of generalised mastocytosis

Energy Technology Data Exchange (ETDEWEB)

Bieler, E.U.; Wohlenberg, H.; Utech, C.

1985-05-01

Bone scans and skeletal X-rays of eight patients with systemic mastocytosis were reviewed. Mast cell infiltration of bone marrow had been proven histologically in every patient. Bone scan and roentgenographic findings are not specific for the disease and do not correlate well in some patients. A generalized increase of uptake was noted in two patients, a generalized decrease of skeletal activity with poor delineation of bony structures was observed in others. A circumscribed increase of activity was observed in some patients, only one patient had a normal bone scan. Roentgenographic examination revealed diffuse sclerosis of trabecular bone in three patients, osteoporosis with collaps of multiple vertebral bodies in three patients, and no abnormalities in two patients.

Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

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Barruet, Emilie; Hsiao, Edward C

2016-01-01

Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

Super bone scans on bone scintigraphy in patients with metastatic bone tumor

International Nuclear Information System (INIS)

Morita, Koichi; Fukunaga, Masao; Otsuka, Nobuaki

1988-01-01

Eight patients with malignant tumor (3 with gastric cancer, 4 with prostatic cancer, 1 with transitional cell carcinoma), which showed diffusely increased uptake of 99m Tc labelled phosphorous compound in axial skeleton (''Super Bone Scan'') on bone scintigraphy were clinically studied. No relationship with its histological type of the tumor was recognized. All cases revealed extremely high serum ALP concentration, which might reflect increased osteoblastic activity. Furthermore, on bone roentgenograms all cases showed predominantly osteosclerotic change in the metastatic bones, while some did locally osteolytic change. In three cases with gastric cancer, although they had diffuse skeletal metastases, two had no evidence of liver metastases. Thus, it seemed that clinical study of patients with ''Super Bone Scan'' was interesting to evaluate the mechanism of accumulation of 99m Tc labelled phosphorous compound to bone and bone metabolism, and the pathophysiology in the pathway of bone metastases. (author)

Bone scintigraphy predicts the risk of spinal cord compression in hormone-refractory prostate cancer

International Nuclear Information System (INIS)

Soerdjbalie-Maikoe, Vidija; Pelger, Rob C.M.; Nijeholt, Guus A.B. Lycklama; Arndt, Jan-Willem; Zwinderman, Aeilko H.; Bril, Herman; Papapoulos, Socrates E.; Hamdy, Neveen A.T.

2004-01-01

In prostate cancer, confirmation of metastatic involvement of the skeleton has traditionally been achieved by bone scintigraphy, although the widespread availability of prostate-specific antigen (PSA) measurements has tended to eliminate the need for this investigation. The potential of bone scintigraphy to predict skeletal-related events, particularly spinal cord compression, after the onset of hormone refractoriness has never been investigated. The aim of this study was to establish whether a new method of evaluating bone scintigraphy would offer a better predictive value for this complication of the metastatic process than is achieved with currently available grading methods. We studied 84 patients with hormone-refractory prostate cancer who had undergone bone scintigraphy at the time of hormone escape. Tumour grading and parameters of tumour load (PSA and alkaline phosphatase activity) were available in all patients. The incidence of spinal cord compression was documented and all patients were followed up until death. Bone scintigraphy was evaluated by the conventional Soloway grading and by an additional analysis determining total or partial involvement of individual vertebrae. In contrast to the Soloway method, the new method was able to predict spinal cord compression at various spinal levels. Our data suggest that there is still a place for bone scintigraphy in the management of hormone-refractory prostate cancer. (orig.)

Effects of caffeic and chlorogenic acids on the rat skeletal system.

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Folwarczna, J; Pytlik, M; Zych, M; Cegieła, U; Nowinska, B; Kaczmarczyk-Sedlak, I; Sliwinski, L; Trzeciak, H; Trzeciak, H I

2015-02-01

Caffeic acid, predominantly as esters linked to quinic acid (chlorogenic acids), is a phenolic acid present at high levels in coffee. The aim of the study was to investigate effects of caffeic and chlorogenic acids on the skeletal system of female rats with normal estrogen levels and estrogen-deficient. Caffeic acid (5 and 50 mg/kg p.o. daily) and chlorogenic acid (100 mg/kg p.o. daily) were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized mature Wistar rats, and their effects were compared with appropriate controls. Moreover, estradiol (0.2 mg/kg p.o. daily) was administered to ovariectomized rats. Bone turnover markers, mass, mineralization and mechanical properties were examined. Although caffeic acid at a low dose exerted some unfavorable effects on the skeletal system, at high doses, caffeic and chlorogenic acids slightly increased mineralization in the tibia and improved mechanical properties of the femoral diaphysis (compact bone). Unlike estradiol, they did not counteract the worsening of the tibial metaphysis bone strength (cancellous bone) and increases in osteocalcin concentration induced by estrogen deficiency. High doses of the phenolic acids slightly favorably affected the rat skeletal system independently of the estrogen status.

Expanding the Description of Spaceflight Effects beyond Bone Mineral Density [BMD]: Trabecular Bone Score [TBS] in ISS Astronauts

Science.gov (United States)

Sibonga, J. D.; Spector, E. R.; King, L. J.; Evans, H. J.; Smith, S. A.

2014-01-01

Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS

Fibrous dysplasia mimicking bone metastasis on both bone scintigraphy and {sup 18}F FDG PET CT: Diagnostic dilemma in a patient with breast cancer

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KC, Sud Hir Suman; Sharma, Punit; Singh, Har Man Deep; Bal, Chand Rasekhar; Kumar, Rake Sh [India Institute of Medical Sciences, New Delhi (India)

2012-12-15

Bone is the most common distant site to which breast cancer metastasizes. Commonly used imaging modalities for imaging bone metastasis are bone scintigraphy, plain radiography, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Although bone scintigraphy gas high sensitivity for detecting bone metastasis, its specificity is low. This is because of the fact that bone scintigraphy images secondary changes in bone rather than just tumor cells {sup 18}F fluorodeoxyglucose ({sup 18}F FDG) PET CT, on the other hand, directly images the tumor cells' glucose metabolism. Unfortunately, similar to bone scintigraphy, benign bone conditions can also show increased {sup 18}F FDG uptake on PET CT, and PET positive asymptomatic fibrous dysplasia can be misinterpreted as a metastasis. Fibrous dysplasia of bone has wide skeletal distribution, with variability of {sup 18}F FDG uptake and CT appearance. It is therefore important to recognize the characteristics of this skeletal dysplasia, to allow differentiation from skeletal metastasis. Bone lesions with {sup 18}F FDG uptake need to be carefully interpreted when evaluating patients with known malignancy. In doubtful cases, fibrous dysplasia should be given as a differential diagnosis and histopathological diagnosis may be warranted, as highlighted in the present case.

Expansion of the CHR bone code system

International Nuclear Information System (INIS)

Farnham, J.E.; Schlenker, R.A.

1976-01-01

This report describes the coding system used in the Center for Human Radiobiology (CHR) to identify individual bones and portions of bones of a complete skeletal system. It includes illustrations of various bones and bone segments with their respective code numbers. Codes are also presented for bone groups and for nonbone materials

Bone scans

International Nuclear Information System (INIS)

Hetherington, V.J.

1989-01-01

Oftentimes, in managing podiatric complaints, clinical and conventional radiographic techniques are insufficient in determining a patient's problem. This is especially true in the early stages of bone infection. Bone scanning or imaging can provide additional information in the diagnosis of the disorder. However, bone scans are not specific and must be correlated with clinical, radiographic, and laboratory evaluation. In other words, bone scanning does not provide the diagnosis but is an important bit of information aiding in the process of diagnosis. The more useful radionuclides in skeletal imaging are technetium phosphate complexes and gallium citrate. These compounds are administered intravenously and are detected at specific time intervals postinjection by a rectilinear scanner with minification is used and the entire skeleton can be imaged from head to toe. Minification allows visualization of the entire skeleton in a single image. A gamma camera can concentrate on an isolated area. However, it requires multiple views to complete the whole skeletal image. Recent advances have allowed computer augmentation of the data received from radionucleotide imaging. The purpose of this chapter is to present the current radionuclides clinically useful in podiatric patients

High Dietary Protein Intake and Protein-Related Acid Load on Bone Health.

Science.gov (United States)

Cao, Jay J

2017-12-01

Consumption of high-protein diets is increasingly popular due to the benefits of protein on preserving lean mass and controlling appetite and satiety. The paper is to review recent clinical research assessing dietary protein on calcium metabolism and bone health. Epidemiological studies show that long-term, high-protein intake is positively associated with bone mineral density and reduced risk of bone fracture incidence. Short-term interventional studies demonstrate that a high-protein diet does not negatively affect calcium homeostasis. Existing evidence supports that the negative effects of the acid load of protein on urinary calcium excretion are offset by the beneficial skeletal effects of high-protein intake. Future research should focus on the role and the degree of contribution of other dietary and physiological factors, such as intake of fruits and vegetables, in reducing the acid load and further enhancing the anabolic effects of protein on the musculoskeletal system.

Insulin signal transduction in skeletal muscle from glucose-intolerant relatives of type 2 diabetic patients [corrected

DEFF Research Database (Denmark)

Storgaard, H; Song, X M; Jensen, C B

2001-01-01

To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects...... phosphorylation in control subjects and IGT relatives, with a tendency for reduced phosphorylation in IGT relatives (P = 0.12). In conclusion, aberrant phosphorylation/activity of IRS-1, PI 3-kinase, and Akt is observed in skeletal muscle from relatives of patients with type 2 diabetes with IGT. However...... resistance in skeletal muscle from relatives of patients with type 2 diabetes....

Bone disease in primary hyperparathyroidism

Science.gov (United States)

Bandeira, Francisco; Cusano, Natalie E.; Silva, Barbara C.; Cassibba, Sara; Almeida, Clarissa Beatriz; Machado, Vanessa Caroline Costa; Bilezikian, John P.

2015-01-01

Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT. PMID:25166047

Study of bone densitometry of mongrel dogs comparing the methods of immersion and radiological densitometry

International Nuclear Information System (INIS)

Grossklauss, D.B.B.S.; Hormaza, J.M.; Rezende, M.A.; Costa, V.E.; Lima, A.; Machado, V.M.V.

2011-01-01

Bone quality is related to the effects of skeletal factors that contribute to resistance, however, can not be judged by measures of mass, but rather by its density. Bone density (BD) is a biophysical parameter of paramount importance, experimental clinic, because it assesses the process of bone mineralization. Calcium is the most abundant mineral in the skeletal system and this is associated with several metabolic functions, such as bone growth. Several pathologies in vertebrates are associated with bone structure that directly affects the locomotor system. Being an endoskeleton, the diagnosis of these diseases becomes abstruse in vivo. Physical characterization of the bone structure of healthy animals post mortem is a valuable tool for comparative diagnosis of animals in vivo. On this basis the project aims to evaluate, discuss and compare the methodologies of radiological density and immersion in water. Concomitantly, the immersion method (IM) is used to evaluate the effect of weight, sex, age and calcium content in bone tissue of the canine strain, correlating with the bone density of the right forelimb region of the humerus-radio-ulnar. (Author)

Selection of bone samples for 239Pu analyses in man

International Nuclear Information System (INIS)

Jee, W.S.S.; Wronski, T.J.; Smith, J.M.; Kimmel, D.B.; Miller, S.C.; Stover, B.J.

1981-01-01

Studies on the skeletal macrodistribution, microdistribution, and toxicity of 239 Pu and studies on bone turnover rates show that trabecular bone sites with high turnover rates have the greatest affinity for 239 Pu. In the adult beagle, these high-turnover, trabecular bone sites also show a higher occurrence of osteosarcomas. Correspondingly, high-turnover bone sites in the human would include the ilium (pelvis) and lumbar vertebrae (LVB), sites that are readily obtainable at autopsy. We recommend that the trabecular bone of the ilium and of the LVB be sampled to determine the skeletal radionuclide content of humans

The biorhythm of human skeletal growth.

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Mahoney, Patrick; Miszkiewicz, Justyna J; Chapple, Simon; Le Luyer, Mona; Schlecht, Stephen H; Stewart, Tahlia J; Griffiths, Richard A; Deter, Chris; Guatelli-Steinberg, Debbie

2018-01-01

Evidence of a periodic biorhythm is retained in tooth enamel in the form of Retzius lines. The periodicity of Retzius lines (RP) correlates with body mass and the scheduling of life history events when compared between some mammalian species. The correlation has led to the development of the inter-specific Havers-Halberg oscillation (HHO) hypothesis, which holds great potential for studying aspects of a fossil species biology from teeth. Yet, our understanding of if, or how, the HHO relates to human skeletal growth is limited. The goal here is to explore associations between the biorhythm and two hard tissues that form at different times during human ontogeny, within the context of the HHO. First, we investigate the relationship of RP to permanent molar enamel thickness and the underlying daily rate that ameloblasts secrete enamel during childhood. Following this, we develop preliminary research conducted on small samples of adult human bone by testing associations between RP, adult femoral length (as a proxy for attained adult stature) and cortical osteocyte lacunae density (as a proxy for the rate of osteocyte proliferation). Results reveal RP is positively correlated with enamel thickness, negatively correlated with femoral length, but weakly associated with the rate of enamel secretion and osteocyte proliferation. These new data imply that a slower biorhythm predicts thicker enamel for children but shorter stature for adults. Our results develop the intra-specific HHO hypothesis suggesting that there is a common underlying systemic biorhythm that has a role in the final products of human enamel and bone growth. © 2017 Anatomical Society.

Axial skeletal CT densitometry

International Nuclear Information System (INIS)

Lampmann, L.E.H.

1982-01-01

Since the discovery of the Roentgen ray a precise and accurate assessment of bone mineral content has been a challenge to many investigators. A number of methods have been developed but no one satisfied. Considering its technical possibilities computed tomography is very promising in determination of bone mineral content (BMC). The new modality enables BMC estimations in the axial skeletal trabecular bone. CT densitometry can be performed on a normal commercially available third generation whole body CT scanner. No dedicated device in a special clinical set-up is necessary. In this study 106 patients, most of them clinically suspected of osteoporosis, were examined. The new method CT densitometry has been evaluated. The results have been correlated to alternative BMC determination methods. (Auth.)

Skeletal diseases. Diagnostic clinical radiology and differential diagnostics. 2. rev. and enl. ed.

International Nuclear Information System (INIS)

Freyschmidt, J.

1997-01-01

The book focuses on the diagnostic evaluation of idiopathic diseases of the skeleton and bone joints, also including the fundamental healing processes of bone fractures, particularly of stress-induced and pathologic fractures. Ample space has been given to the description and imaging of the course of diseases under treatment by up-to-date therapies, as e.g. for ostitis deformans Paget's disease, or skeletal metastases. This second edition of the book incorporates the progress achieved over the last five years in skeletal diagnostics. The advances in this field have been resulting from basic research work, for instance in molecular biology, or from a variety of completed studies relating to clinical medicine, laboratory chemistry, histopathology and radiology of skeletal diseases, and from experience obtained with the diagnostic radiology methods and techniques, with the potentials and constraints of magnetic resonance imaging (MRI) today being more critically assessed than five years ago. MRI is a modality currently meeting with interest in the context of search for additional diagnostic information, new definition of complete pictures of diseases, or false or overinterpretation of diagnostic findings. (orig./MG). 431 figs [de

Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

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Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

2017-06-25

Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Following Surgically Assisted Rapid Palatal Expansion, Do Tooth-Borne or Bone-Borne Appliances Provide More Skeletal Expansion and Dental Expansion?

Science.gov (United States)

Hamedi-Sangsari, Adrien; Chinipardaz, Zahra; Carrasco, Lee

2017-10-01

The aim of this study was to compare outcome measurements of skeletal and dental expansion with bone-borne (BB) versus tooth-borne (TB) appliances after surgically assisted rapid palatal expansion (SARPE). This study was performed to provide quantitative measurements that will help the oral surgeon and orthodontist in selecting the appliance with, on average, the greatest amount of skeletal expansion and the least amount of dental expansion. A computerized database search was performed using PubMed, EBSCO, Cochrane, Scopus, Web of Science, and Google Scholar on publications in reputable oral surgery and orthodontic journals. A systematic review and meta-analysis was completed with the predictor variable of expansion appliance (TB vs BB) and outcome measurement of expansion (in millimeters). Of 487 articles retrieved from the 6 databases, 5 articles were included, 4 with cone-beam computed tomographic (CBCT) data and 1 with non-CBCT 3-dimensional cast data. There was a significant difference in skeletal expansion (standardized mean difference [SMD], 0.92; 95% confidence interval [CI], 0.54-1.30; P appliances. However, there was no significant difference in dental expansion (SMD, 0.05; 95% CI, -0.24 to 0.34; P = .03). According to the literature, to achieve more effective skeletal expansion and minimize dental expansion after SARPE, a BB appliance should be favored. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Skeletal metastases from breast cancer: uptake of 18F-fluoride measured with positron emission tomography in correlation with CT

International Nuclear Information System (INIS)

Petren-Mallmin, M.; Andreasson, I.; Bergh, J.; Ljunggren, Oe.; Ahlstroem, H.; Antoni, G.; Laangstroem, B.; Bergstroem, M.

1998-01-01

Objective. To characterise the uptake of 18 F in skeletal metastases from breast cancer using positron emission tomography (PET) and to relate these findings to the appearance on CT. Patients and design. PET with 18 F and CT were performed in five patients with multiple skeletal metastases from breast cancer. The CT characteristics were analysed in areas with high uptake on the PET study. Dynamic PET imaging of the skeletal kinetics of the 18 F-fluoride ion were included. Results. The areas of abnormal high accumulation of 18 F correlated well with the pathological appearance on CT. Lytic as well as sclerotic lesions had markedly higher uptake than normal bone, with a 5-10 times higher transport rate constant for trapping of the tracer in the metastatic lesions than in normal bone. Conclusion. PET with 18 F-fluoride demonstrates very high uptake in lytic and sclerotic breast cancer metastases. (orig.)

Bone healing and bone substitutes.

Science.gov (United States)

Costantino, Peter D; Hiltzik, David; Govindaraj, Satish; Moche, Jason

2002-02-01

With the advent of new biomaterials and surgical techniques, the reconstructive surgeon has a wider range of treatment modalities for the rehabilitation and reconstruction of craniofacial skeletal deformities than ever before. These innovative substances act as true bone graft substitutes, thereby allowing the surgeon to avoid the use of autogenous bone grafts and their associated donor site morbidity. Surgeons have long been interested in producing a composite graft that can heal faster by induction, incorporate with surrounding tissues, and be remodeled to resemble native bone. Currently, there are a host of bone graft substitutes available that vary in both their composition and properties. Craniomaxillofacial surgeons must therefore become comfortable with numerous biomaterials to best tailor the treatment for each patient individually. Ongoing investigations into the next phase of tissue engineering will continue to bring us closer to the ability to regenerate or replace bone.

Metabolic, endocrine, and related bone diseases

International Nuclear Information System (INIS)

Rogers, L.F.

1987-01-01

Bone is living tissue, and old bone is constantly removed and replaced with new bone. Normally this exchange is in balance, and the mineral content remains relatively constant. This balance may be disturbed as a result of certain metabolic and endocrinologic disorders. The term dystrophy, referring to a disturbance of nutrition, is applied to metabolic and endocrine bone diseases and should be distinguished from the term dysplasia, referring to a disturbance of bone growth. The two terms are easily confused but are not interchangeable. Metabolic bone disease is caused by endocrine imbalance, vitamin deficiency or excess, and other disturbances in bone metabolism leading to osteoporosis and osteomalacia

Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis.

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Raisingani, Manish; Preneet, Brar; Kohn, Brenda; Yakar, Shoshana

2017-06-01

Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases diagnosed in childhood. Childhood and adolescent years are also the most important period for growth in height and acquisition of skeletal bone mineral density (BMD). The growth hormone (GH)/insulin like growth factor -1 (IGF-1) axis which regulates growth, is affected by T1DM, with studies showing increased GH and decreased IGF-1 levels in children with T1DM. There is conflicting data as to whether adolescents with TIDM are able to achieve their genetically-determined adult height. Furthermore, data support that adolescents with T1DM have decreased peak BMD, although the pathophysiology of which has not been completely defined. Various mechanisms have been proposed for the decrease in BMD including low osteocalcin levels, reflecting decreased bone formation; increased sclerostin, an inhibitor of bone anabolic pathways; and increased leptin, an adipocytokine which affects bone metabolism via central and peripheral mechanisms. Other factors implicated in the increased bone resorption in T1DM include upregulation of the osteoprotegerin/ receptor-activator of the nuclear factor-κB ligand pathway, elevated parathyroid hormone levels, and activation of other cytokines involved in chronic systemic inflammation. In this review, we summarize the clinical studies that address the alterations in the GH/IGF-I axis, linear growth velocity, and BMD in children and adolescents with T1DM; and we review the possible molecular mechanisms that may contribute to an attenuation of linear growth and to the reduction in the acquisition of peak bone mass in the child and adolescent with T1DM. Copyright © 2017. Published by Elsevier Ltd.

Gonadal steroids and bone metabolism in men.

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Leder, Benjamin

2007-06-01

Over the past decade, our increasing awareness of the clinical importance of osteoporosis in men has stimulated intense interest in trying to better understand male skeletal physiology and pathophysiology. The present review focuses on a major focus of research in this area, namely the attempt to define the influence and therapeutic potential of gonadal steroids in male bone metabolism. Building on previous work defining the relative roles of androgens and estrogens in the developing male skeleton and in maintaining normal bone turnover, recent studies have begun to define these issues from epidemiologic, physiologic and therapeutic perspectives. With access to data from large prospectively defined populations of men, investigators are confirming and challenging existing hypotheses and forwarding new concepts. Clinical trials have expanded beyond standard androgen replacement studies to explore more complex hormonal interventions. Physiologic investigation has continued to probe the mechanisms underlying the differential and independent roles of androgens and estrogens in male bone metabolism. Recent work has added significantly to our understanding of the role of gonadal steroids in male skeletal physiology. Nonetheless, further research is necessary to build on these initial human studies and to capitalize on rapidly emerging advances in our understanding of the basic biology of bone metabolism.

Clinical evaluation of skeletal scintigraphy with sup(99m)Tc-pyrophosphate

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Sugiura, I; Sasaki, T; Kaneko, M; Watanabe, M [Nagoya Univ. (Japan). Faculty of Medicine

1975-04-01

Following about 10 mCi of intravenous administration of sup(99m)Tc-pyrophosphate, skeletal scintiphotography was performed in various skeletal diseases. Skeletal scintiphotograms were taken at about 2 to 3 hours after the administration of the radioisotope with Nuclear Chicago Rho/Gamma III scinticamera. The frontal, occipital and bilateral views of the skull, posterior and lateral views of the spine, anterior and posterior views of ribs, anterior and posterior views of the pelvis and either anterior and posterior views of extremities were scintiphotographed. 17 cases were studied of primary bone tumor (7 benign, 10 malignant), 20 cases of osseous metastasis and 20 cases of non-tumorous conditions. In malignant and benign bone tumors radioactivity is increased at the site of bony changes except for myeloma and leukaemia. In osseous metastasis radioactivity is increased at the site of lesion, even in the early stage. In non-tumorous conditions, radioactivity is also increased at the site of bony changes except for old healed osteomyelitis, old healed tuberculosis of bone and osteoporosis in Cushing's syndrome.

Morbidity, rickets and long-bone growth in post-medieval Britain--a cross-population analysis.

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Pinhasi, R; Shaw, P; White, B; Ogden, A R

2006-01-01

Vitamin D deficiency rickets is associated with skeletal deformities including swollen rib junctions, bowing of the legs, and the flaring and fraying of the wrist and long-bone metaphyses. There is, however, scarce information on the direct effect of rickets on skeletal growth in either present or past populations. The study investigated the effect of vitamin D deficiency rickets on long-bone growth in two post-medieval skeletal populations from East London (Broadgate and Christ Church Spitalfields). Subsequently, inter-population growth variations in relation to non-specific environmental stress (dental enamel defects), industrialization, urbanization and socio-economic status during infancy (birth to 3 years) and early childhood (3-7 years) were examined. Data on long-bone diaphyseal length dimensions and stress indicators of 234 subadults from Anglo-Saxon, late medieval and post-medieval archaeological skeletal samples were analysed using both linear and non-linear growth models. Rickets had no effect on the growth curves for any of the long bones studied. However, pronounced variations in growth between the four populations were noted, mainly during infancy. The diaphyseal length of long bones of Broadgate were significantly smaller-per-age than those of Spitalfields and the other samples up to the age of 4 years, and were associated with a high prevalence of enamel defects during early infancy. Socio-economic status, rather than urbanization, industrialization or rickets, was the central factor behind the observed differences in growth among the post-medieval populations. The observed inter-population growth variations were only significant during infancy.

Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

DEFF Research Database (Denmark)

Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

2011-01-01

Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk of f...

Caffeine at a Moderate Dose Did Not Affect the Skeletal System of Rats with Streptozotocin-Induced Diabetes

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Joanna Folwarczna

2017-10-01

Full Text Available Diabetes may lead to the development of osteoporosis. Coffee drinking, apart from its health benefits, is taken into consideration as an osteoporosis risk factor. Data from human and animal studies on coffee and caffeine bone effects are inconsistent. The aim of the study was to investigate effects of caffeine at a moderate dose on the skeletal system of rats in two models of experimental diabetes induced by streptozotocin. Effects of caffeine administered orally (20 mg/kg aily for four weeks were investigated in three-month-old female Wistar rats, which, two weeks before the start of caffeine administration, received streptozotocin (60 mg/kg, intraperitoneally alone or streptozotocin after nicotinamide (230 mg/kg, intraperitoneally. Bone turnover markers, mass, mineral density, histomorphometric parameters, and mechanical properties were examined. Streptozotocin induced diabetes, with profound changes in the skeletal system due to increased bone resorption and decreased bone formation. Although streptozotocin administered after nicotinamide induced slight increases in glucose levels at the beginning of the experiment only, slight, but significant unfavorable changes in the skeletal system were demonstrated. Administration of caffeine did not affect the investigated skeletal parameters of rats with streptozotocin-induced disorders. In conclusion, caffeine at a moderate dose did not exert a damaging effect on the skeletal system of diabetic rats.

Caffeine at a Moderate Dose Did Not Affect the Skeletal System of Rats with Streptozotocin-Induced Diabetes.

Science.gov (United States)

Folwarczna, Joanna; Janas, Aleksandra; Cegieła, Urszula; Pytlik, Maria; Śliwiński, Leszek; Matejczyk, Magdalena; Nowacka, Anna; Rudy, Karolina; Krivošíková, Zora; Štefíková, Kornélia; Gajdoš, Martin

2017-10-30

Diabetes may lead to the development of osteoporosis. Coffee drinking, apart from its health benefits, is taken into consideration as an osteoporosis risk factor. Data from human and animal studies on coffee and caffeine bone effects are inconsistent. The aim of the study was to investigate effects of caffeine at a moderate dose on the skeletal system of rats in two models of experimental diabetes induced by streptozotocin. Effects of caffeine administered orally (20 mg/kg aily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of caffeine administration, received streptozotocin (60 mg/kg, intraperitoneally) alone or streptozotocin after nicotinamide (230 mg/kg, intraperitoneally). Bone turnover markers, mass, mineral density, histomorphometric parameters, and mechanical properties were examined. Streptozotocin induced diabetes, with profound changes in the skeletal system due to increased bone resorption and decreased bone formation. Although streptozotocin administered after nicotinamide induced slight increases in glucose levels at the beginning of the experiment only, slight, but significant unfavorable changes in the skeletal system were demonstrated. Administration of caffeine did not affect the investigated skeletal parameters of rats with streptozotocin-induced disorders. In conclusion, caffeine at a moderate dose did not exert a damaging effect on the skeletal system of diabetic rats.

Primary non-Hodgkin lymphoma of skeletal muscle: imaging findings

International Nuclear Information System (INIS)

Zhou Liangping; Peng Weijun; Tang Feng; Mao Jian; Yang Wentao

2006-01-01

Objective: To analyze the imaging manifestations of primary non-Hodgkin lymphoma of skeletal muscle and improve the recognition of this rare disease. Methods: Five cases of primary non- Hodgkin lymphoma of skeletal muscle proved pathologically underwent imaging exam, including MRI and CT in 3 cases, only MRI in 1 case, only CT in 1 case, X-ray in 2 cases and bone scintigraphy in 2 cases. Results: Diffuse enlargements of involved muscle with presentation of overall configuration were observed in all five cases. All 4 cases manifested as homogeneous soft masses, which is isoattenuating to normal muscle on unenhanced CT images. After intravenous injection of contrast media, the masses enhanced homogeneously and slightly (2 cases) or moderately (1 case) on CT images. The lesions were homogenous and had isointense or slightly low signal intensity compared with that of uninvolved muscle on T 1 -weighted images and high signal intensity on T 2 -weighted images. After intravenous injection of contrast media, all 2 cases enhanced homogeneously and moderately with the enhanced signal intensity of involved muscle greatly higher than that of uninvolved muscle on MR images. Two cases of X-ray plain showed no destruction of bone and 2 cases of bone scintigraphy exams showed increased radiotracer uptake of involved muscle with no infiltration of bone marrow. Conclusion: There are several characteristics on the imaging of primary non-Hodgkin lymphoma of skeletal muscle. MRI is the optimal imaging method for the diagnosis of this disease. (authors)

SKELETAL MORPHOLOGY OF THE FORELIMB OF MYRMECOPHAGA TRIDACTYLA.

Science.gov (United States)

Sesoko, Natália Ferreira; Rahal, Sheila Canevese; Bortolini, Zara; de Souza, Lívia Pasini; Vulcano, Luiz Carlos; Monteiro, Frederico Ozanan Barros; Teixeira, Carlos Roberto

2015-12-01

Anteater forelimbs are morphologically adapted to obtain food and to provide defense and locomotion. Four species are known, but there are few anatomical studies presenting the morphologic features of each species. The aim of this study was to describe the skeletal morphology of the giant anteater (Myrmecophaga tridactyla) forelimb. Pictures and schematic drawings of six cadavers were created to show the bone morphology. In addition, radiographs and computed tomographs were obtained. The skeletal structure of the forelimb had several notable anatomical features. The scapula had two spines, with apparent differences between infant and adult animals. The humerus had a pectoral ridge, a pectoral tubercle, and a pronounced medial epicondyle that represent the origins of muscles important for fossorial activity. The radius had cranial, lateral, and caudal ridges that became more prominent in older animals, and the distal condyle joint provided enhanced support of the dorsal articulation for the manus. Knowledge of the bone morphology of the forelimb generates a better understanding of giant anteater habits and helps in the diagnosis of skeletal abnormalities and in the routine medical assessment of this species.

Clinical significance of bone age estimation

International Nuclear Information System (INIS)

Heinrich, U.E.

1986-01-01

Skeletal development is an important maturity indicator during childhood. In clinical practice determination of skeletal age is helpful for the diagnosis of disorders of growth and development. Most hormones have specific effects on skeletal maturation. Thus, different disease states (growth disorders, disorders of pubertal development, chornic disorders of the bowels, kidneys, heart etc.) are characterized by retardation or acceleration of skeletal maturation. Therapeutic effects as well as side effects of hormones can be monitored by skeletal age determination. Typical disharmonic patterns in the appearance of bone centres of hand and wrist have been found in certain disorders of development. (orig.) [de

The use of bone age in clinical practice - Part 2

DEFF Research Database (Denmark)

Martin, D.D.; Binder, Gitte Sommer; Ranke, M.B.

2011-01-01

and measures of bone lengths, width, thickness and cortical thickness should always be evaluated in relation to a child's height and BA, especially around puberty. The use of skeletal maturity, assessed on a radiograph alone to estimate chronological age for immigration authorities or criminal courts...

A modern documented Italian identified skeletal collection of 2127 skeletons: the CAL Milano Cemetery Skeletal Collection.

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Cattaneo, Cristina; Mazzarelli, Debora; Cappella, Annalisa; Castoldi, Elisa; Mattia, Mirko; Poppa, Pasquale; De Angelis, Danilo; Vitello, Antonio; Biehler-Gomez, Lucie

2018-06-01

The CAL Milano Cemetery Skeletal Collection is a modern and continuously growing identified osteological collection of 2127 skeletons under study in the Laboratorio di Antropologia e Odontologia Forense (LABANOF) in the Department of Biomedical Sciences for Health of the University of Milan (Italy), and part of the Collezione Antropologica LABANOF (CAL). The collection presents individuals of both sexes and of all age groups with a high representation of the elderly and an interesting sample of infants. Each individual is associated with a documentation that includes sex, age-at-death, dates of birth and death, and a death certificate that specifies the exact cause of death and the chain of events that led to it (related pathological conditions or traumatic events). It was also possible to recover for several individuals the autopsy reports and antemortem photographs. This documented osteological collection is of crucial interest in physical and forensic anthropology: it provides unique teaching opportunities and more importantly considerable research possibilities to test and develop sex and age estimation methods, investigate key subjects of forensic relevance and discuss pathological markers, among others. The aim of this paper is to introduce the CAL Milano Cemetery Skeletal Collection as a new identified skeletal collection and present its research and teaching potential. Copyright © 2018 Elsevier B.V. All rights reserved.

Future of bisphosphonates and denosumab for men with advanced prostate cancer

International Nuclear Information System (INIS)

Iranikhah, Maryam; Stricker, Steve; Freeman, Maisha Kelly

2014-01-01

Prostate cancer is the most common cancer occurring in American men of all races. It is also the second leading cause of cancer death among men in the USA. Bone metastasis is a frequent occurrence in men with advanced prostate cancer, with skeletal-related events being a common complication and having negative consequences, leading to severe pain, increased health care costs, increased risk of death, and decreased quality of life for patients. Bone loss can also result from antiandrogen therapy, which can further contribute to skeletal-related events. Treatment with antiresorptive agents bisphosphonates, and the newly approved denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, has been shown to reduce the risk of skeletal-related complications and prevent treatment-induced bone loss in patients with advanced prostate cancer. This review discusses the role of antiresorptive agents bisphosphonates and RANK-L inhibitor in the current treatment of advanced prostate cancer by examining the primary literature and also focuses on the likely role of the bisphosphonates in the treatment of advanced prostate cancer in the future

Decreased bone uptake of technetium-99m polyphosphate in thalassemia major

International Nuclear Information System (INIS)

Valdez, V.A.; Jacobstein, J.G.

1980-01-01

Bone scans were performed with Tc-99m stannous polyphosphate on four patients with thalassemia major. Three of the scans show generalized decrease in skeletal uptake of the radiopharmaceutical, associated with renal enlargement and markedly increased renal radioactivity. The skeletal findings are consistent with the known bone abnormalities in thalassemia major, which are secondary to the extensive marrow hyperplasia and include loss of trabeculae and cortical thinning with consequent loss of bone mass. The increased renal uptake is probably due in part to the increased renal excretion (secondary to the poor bone uptake) and in part to the tubular dilatation and renal enlargement associated with thalassemia major. In addition, the presence of excessive amounts of iron in these patients may play a role in both the skeletal and renal findings

High fluoride and low calcium levels in drinking water is associated with low bone mass, reduced bone quality and fragility fractures in sheep.

Science.gov (United States)

Simon, M J K; Beil, F T; Rüther, W; Busse, B; Koehne, T; Steiner, M; Pogoda, P; Ignatius, A; Amling, M; Oheim, R

2014-07-01

Chronic environmental fluoride exposure under calcium stress causes fragility fractures due to osteoporosis and bone quality deterioration, at least in sheep. Proof of skeletal fluorosis, presenting without increased bone density, calls for a review of fracture incidence in areas with fluoridated groundwater, including an analysis of patients with low bone mass. Understanding the skeletal effects of environmental fluoride exposure especially under calcium stress remains an unmet need of critical importance. Therefore, we studied the skeletal phenotype of sheep chronically exposed to highly fluoridated water in the Kalahari Desert, where livestock is known to present with fragility fractures. Dorper ewes from two flocks in Namibia were studied. Chemical analyses of water, blood and urine were executed for both cohorts. Skeletal phenotyping comprised micro-computer tomography (μCT), histological, histomorphometric, biomechanical, quantitative backscattered electron imaging (qBEI) and energy-dispersive X-ray (EDX) analysis. Analysis was performed in direct comparison with undecalcified human iliac crest bone biopsies of patients with fluoride-induced osteopathy. The fluoride content of water, blood and urine was significantly elevated in the Kalahari group compared to the control. Surprisingly, a significant decrease in both cortical and trabecular bones was found in sheep chronically exposed to fluoride. Furthermore, osteoid parameters and the degree and heterogeneity of mineralization were increased. The latter findings are reminiscent of those found in osteoporotic patients with treatment-induced fluorosis. Mechanical testing revealed a significant decrease in the bending strength, concurrent with the clinical observation of fragility fractures in sheep within an area of environmental fluoride exposure. Our data suggest that fluoride exposure with concomitant calcium deficit (i) may aggravate bone loss via reductions in mineralized trabecular and cortical bone

Bone/soft-tissue enrichment ratio in skeletal scintiscanning

International Nuclear Information System (INIS)

Reuschel, W.

1982-01-01

The thesis aimed at establishing normal values for the enrichment intensity of sup(99m)Tc-MDP above the sacrum (S) as reference point for spongy bones in relation to soft-tissue (ST) enrichment (S/St ratio). A normal range for S/ST was determined for five age groups which was given separately for males and females. In addition, the question was examined what causes there could be for S/ST exceeding, the norm or an increased F/ST ratio (F=femur centre) between bone and soft tissue. The question was studied whether or not beniguity or malignancy of a base disease has an important influence on F/ST values. Dependence of F/ST values from primary tumour localization and the tendency of metastatic spread in bones were investigated in malignoma patients. In addition, an assessment was made of what correlation existed, between the laboratory parameters measured, particularly alkaline phosphatase, and the F/ST values. The questions were examined what correlation existed between the F/ST values established and scintiscan findings; whether or not solitary radionuclide enrichments or multiple foci were found in the scintiscan; and what influence the number of foci had on the F/ST values. In tumour patients, the question examined what correlation existed between a tumour-specific treatment and the F/ST values. (orig./MG) [de

Automated radiogrammetry is a feasible method for measuring bone quality and bone maturation in severely disabled children

International Nuclear Information System (INIS)

Mergler, Sandra; Man, Stella A. de; Boot, Annemieke M.; Heus, Karen G.C.B.B.; Huijbers, Wim A.R.; Rijn, Rick R. van; Penning, Corine; Evenhuis, Heleen M.

2016-01-01

Children with severe neurological impairment and intellectual disability are prone to low bone quality and fractures. We studied the feasibility of automated radiogrammetry in assessing bone quality in this specific group of children. We measured outcome of bone quality and, because these children tend to have altered skeletal maturation, we also studied bone age. We used hand radiographs obtained in 95 children (mean age 11.4 years) presenting at outpatient paediatric clinics. We used BoneXpert software to determine bone quality, expressed as paediatric bone index and bone age. Regarding feasibility, we successfully obtained a paediatric bone index in 60 children (63.2%). The results on bone quality showed a mean paediatric bone index standard deviation score of -1.85, significantly lower than that of healthy peers (P < 0.0001). Almost 50% of the children had severely diminished bone quality. In 64% of the children bone age diverged more than 1 year from chronological age. This mostly concerned delayed bone maturation. Automated radiogrammetry is feasible for evaluating bone quality in children who have disabilities but not severe contractures. Bone quality in these children is severely diminished. Because bone maturation frequently deviated from chronological age, we recommend comparison to bone-age-related reference values. (orig.)

Automated radiogrammetry is a feasible method for measuring bone quality and bone maturation in severely disabled children

Energy Technology Data Exchange (ETDEWEB)

Mergler, Sandra [Erasmus MC, Department of General Practice and Intellectual Disability Medicine, University Medical Centre, Rotterdam (Netherlands); Care and Service Centre for People with Intellectual Disabilities, Medical Department ASVZ, Sliedrecht (Netherlands); Man, Stella A. de [Amphia Hospital, Department of Paediatrics, Breda (Netherlands); Boot, Annemieke M. [University of Groningen, Department of Paediatric Endocrinology, University Medical Centre Groningen, Groningen (Netherlands); Heus, Karen G.C.B.B. [Erasmus MC, Department of General Paediatrics, Sophia Children' s Hospital, University Medical Centre, Rotterdam (Netherlands); Huijbers, Wim A.R. [Beatrix Hospital, Department of Paediatrics, Gorinchem (Netherlands); Rijn, Rick R. van [Emma Children' s Hospital/Academic Medical Centre, Department of Radiology, Amsterdam (Netherlands); Penning, Corine; Evenhuis, Heleen M. [Erasmus MC, Department of General Practice and Intellectual Disability Medicine, University Medical Centre, Rotterdam (Netherlands)

2016-06-15

Children with severe neurological impairment and intellectual disability are prone to low bone quality and fractures. We studied the feasibility of automated radiogrammetry in assessing bone quality in this specific group of children. We measured outcome of bone quality and, because these children tend to have altered skeletal maturation, we also studied bone age. We used hand radiographs obtained in 95 children (mean age 11.4 years) presenting at outpatient paediatric clinics. We used BoneXpert software to determine bone quality, expressed as paediatric bone index and bone age. Regarding feasibility, we successfully obtained a paediatric bone index in 60 children (63.2%). The results on bone quality showed a mean paediatric bone index standard deviation score of -1.85, significantly lower than that of healthy peers (P < 0.0001). Almost 50% of the children had severely diminished bone quality. In 64% of the children bone age diverged more than 1 year from chronological age. This mostly concerned delayed bone maturation. Automated radiogrammetry is feasible for evaluating bone quality in children who have disabilities but not severe contractures. Bone quality in these children is severely diminished. Because bone maturation frequently deviated from chronological age, we recommend comparison to bone-age-related reference values. (orig.)

Retrospective review to determine the utility of follow-up skeletal surveys in child abuse evaluations when the initial skeletal survey is normal

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Kachelmeyer Andrea

2011-09-01

Full Text Available Abstract Objective The AAP recommends that a follow-up skeletal survey be obtained for all children Methods A retrospective review of radiology records from September 1, 1998 - January 31, 2007 was conducted. Suspected victims of child abuse who were Results Forty-seven children had a negative initial skeletal survey and were included for analysis. The mean age was 6.9 months (SD 5.7; the mean number of days between skeletal surveys was 18.7 (SD 10.1 Four children (8.5% had signs of healing bone trauma on a follow-up skeletal survey. Three of these children (75% had healing rib fractures and one child had a healing proximal humerus fracture. The findings on the follow-up skeletal survey yielded forensically important information in all 4 cases and strengthened the diagnosis of non-accidental trauma. Conclusion 8.5 percent of children with negative initial skeletal surveys had forensically important findings on follow-up skeletal survey that increased the certainty of the diagnosis of non-accidental trauma. A follow-up skeletal survey can be useful even when the initial skeletal survey is negative.

A distinct subtype of ''metatropic dysplasia variant'' characterised by advanced carpal skeletal age and subluxation of the radial heads

International Nuclear Information System (INIS)

Nishimura, G.; Satoh, Masato; Aihara, Toshinori; Aida, Noriko; Yamamoto, Takehisa; Ozono, Keiichi

1998-01-01

Background. ''Metatropic dysplasia variants'' are a group of bone dysplasias whose skeletal abnormalities are similar to, but milder than, those of classical metatropic dysplasia. The genetic and phenotypic heterogeneity has not been thoroughly elucidated. Objective. The objective was to designate a distinct subtype of these metatropic dysplasia variants. Materials and methods. The subjects were four Japanese patients, two sporadic cases and two siblings, who all had identical skeletal changes. The radiological features in these patients were compared with those of previously reported metatropic dysplasia variants. Results. Moderate platyspondyly with pear-shaped and/or anterior-tongued vertebral bodies, halberd pelvis, and dumbbell deformity of the tubular bones were regarded as hallmarks of metatropic dysplasia variants. The peculiar skeletal change in our patients was advanced carpal skeletal age in childhood, unlike most patients reported as metatropic dysplasia variants who manifest delayed carpal ossification. Another hallmark was congenital dislocation of the radial heads. A description of a patient with similar skeletal changes was found in the literature. Conclusion. These patients are considered to represent a distinct subgroup of metatropic dysplasia variants. It remains unknown whether the present siblings represent an autosomal recessive trait or an autosomal dominant trait with germinal mosaicism related to increased paternal age. (orig.)

Clodronate Therapy in Patients with Breast Cancer and Bone Metastases

International Nuclear Information System (INIS)

Saber, M.M.; Shouman, T.

2003-01-01

To assess whether clodronate can reduce frequency of skeletal morbidity in women with lytic bone metastases from breast cancer. Methods: Between 1997 and 2001,167 patients with stage IV breast cancer with bone metastases, were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for 12 months, in addition to the standard specific anti cancer therapy (87 patients) or standard anti cancer therapy only (80 patients). Skeletal complications, including pathological fractures, the need for radiation to bone or bone surgery, spinal cord compression and hypercalcaemia (a serum calcium concentration above 12 mg per deci liter (3.0 mmol per liter) or elevated to any degree and requiring treatment) were assessed monthly. Bone pam. use of analgesic drugs, performance status and quality of life were assessed throughout the trial. Results: There was no significant difference between the two groups at study entry regarding clinical characteristics. The median time for first skeletal complication was ,significantly less in the control group (6.1 vs 9.7 months, ρ=0.05). The proportion of patients who had any skeletal complication in the clodronate group than the control group, but the difference was insignificant (ρ 0.09). Clodronate was generally well tolerated and the main side effects were constipation (32%) flatulence/dyspepsia (17%) and anorexia (8%). The overall survival was not affected by clodronate therapy. The median survival was 14 months In the clodronate group and 13.8 months in the control group. Conclusions: Clodronate is an effective supplement to conventional anticancer treatment for breast cancer with bone metastasis. It reduces skeletal complications and relieves symptoms associated with lytic bone lesions. Further clinical trials that recruit a larger number of patients will be needed to clearly define the role of clodronate in metastatic breast cancer

Cortical bone metastases

International Nuclear Information System (INIS)

Davis, T.M. Jr.; Rogers, L.F.; Hendrix, R.W.

1986-01-01

Twenty-five cases of bone metastases involving the cortex alone are reviewed. Seven patients had primary lung carcinoma, while 18 had primary tumors not previously reported to produce cortical bone metastases (tumors of the breast, kidney, pancreas, adenocarcinoma of unknown origin, multiple myeloma). Radiographically, these cortical lesions were well circumscribed, osteolytic, and produced soft-tissue swelling and occasional periosteal reaction. A recurrent pattern of metadiaphyseal involvement of the long bones of the lower extremity (particularly the femur) was noted, and is discussed. Findings reported in the literature, review, pathophysiology, and the role of skeletal radiographs, bone scans, and CT scans in evaluating cortical bone metastases are addressed

Is there a relation between local bone quality as assessed on panoramic radiographs and alveolar bone level?

Science.gov (United States)

Nackaerts, Olivia; Gijbels, Frieda; Sanna, Anna-Maria; Jacobs, Reinhilde

2008-03-01

The aim was to explore the relation between radiographic bone quality on panoramic radiographs and relative alveolar bone level. Digital panoramic radiographs of 94 female patients were analysed (mean age, 44.5; range, 35-74). Radiographic density of the alveolar bone in the premolar region was determined using Agfa Musica software. Alveolar bone level and bone quality index (BQI) were also assessed. Relationships between bone density and BQI on one hand and the relative loss of alveolar bone level on the other were assessed. Mandibular bone density and loss of alveolar bone level were weakly but significantly negatively correlated for the lower premolar area (r = -.27). The BQI did not show a statistically significant relation to alveolar bone level. Radiographic mandibular bone density on panoramic radiographs shows a weak but significant relation to alveolar bone level, with more periodontal breakdown for less dense alveolar bone.

Simulation of 239Pu location in trabecular bone: a computerized model of adult endosteal bone remodeling and its interaction with injected 239Pu

International Nuclear Information System (INIS)

Kimmel, D.B.; Jee, W.S.S.

1979-01-01

A computer simulation of the relationship of bone microanatomic metabolic activity to the microscopic location of 239 Pu in bone has been attempted. The model incorporates the rate of bone turnover, cell location and density, bone resorptive activity (as it removes 239 Pu from bone), bone formation activity (as it buries 239 Pu in bone), recycling of 239 Pu, and liver translocation of 239 Pu to bone, such that the skeletal retention curve for 239 Pu injected in monomeric form into the young adult beagle is matched. The eventual aim of this work is to calculate the radiation dose to bone cells, knowing the relative location of 239 Pu deposited in bone and the cells that reside at bone surfaces as it changes throughout the lifespan of an animal. Early results indicate that osteosarcoma incidence may be proportional to the number of alpha hits which occur to osteoprogenitor cells and osteoblasts, the dividing cell population found near surfaces where bone turnover is in progress

Detection of bone metastasis of prostate cancer. Comparison of whole-body MRI and bone scintigraphy

International Nuclear Information System (INIS)

Ketelsen, D.; Roethke, M.; Aschoff, P.; Lichy, M.P.; Claussen, C.D.; Schlemmer, H.P.; Merseburger, A.S.; Reimold, M.

2008-01-01

Purpose: prostate cancer continues to be the third leading cancer-related mortality of western men. Early diagnosis of bone metastasis is important for the therapy regime and for assessing the prognosis. The standard method is bone scintigraphy. Whole-body MRI proved to be more sensitive for early detection of skeletal metastasis. However, studies of homogenous tumor entities are not available. The aim of the study was to compare bone scintigraphy and whole-body MRI regarding the detection of bone metastasis of prostate cancer. Materials and methods: 14 patients with histologically confirmed prostate cancer and a bone scintigraphy as well as whole-body MRI within one month were included. The mean age was 68 years. Scintigraphy was performed using the planar whole-body technique (ventral and dorsal projections). Suspect areas were enlarged. Whole-body MRI was conducted using native T1w and STIR sequences in the coronary plane of the whole body, sagittal imaging of spine and breath-hold STIR and T1w-Flash-2D sequences of ribs and chest. Bone scintigraphy and whole-body MRI were evaluated retrospectively by experienced radiologists in a consensus reading on a lesion-based level. Results: whole-body MRI detected significantly more bone metastasis (p = 0.024). 96.4% of the demonstrated skeletal metastases in bone scintigraphy were founded in whole-body MRI while only 58.6% of the depicted metastases in MRI were able to be located in scintigraphy. There was no significant difference regarding bone metastasis greater than one centimeter (p = 0.082) in contrast to metastasis less than one centimeter (p = 0.035). Small osteoblastic metastases showed a considerably higher contrast in T1w sequences than in STIR imaging. Further advantages of whole-body MRI were additional information about extra-osseous tumor infiltration and their complications, for example stenosis of spinal canal or vertebral body fractures, found in 42.9% of patients. (orig.)

The influence of dietary crude protein intake on bone and mineral metabolism in sheep

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T.S. Brand

1999-07-01

Full Text Available Increased dietary protein consumption is thought to cause calciuresis, a negative calcium balance and increased bone loss that may result in skeletal deformities and fracture. To explore this hypothesis, 40 approximately 100-day-old meat-type Merino ram lambs were fed, for 6 months, diets with an increasing crude protein (CP content (114, 142, 171 and 190 g/kg DM but approximately on an iso-nutrient basis with regard to metabolisable energy, calcium and phosphorus. Increased protein consumption modestly (NS enhanced calciuresis and resulted in significant (P < 0.01 limb skewness. This could not, however, be ascribed to osteopaenic bones, and compared with animals consuming lower protein rations, the bone mineral density (BMD and vertebral trabecular bone volume of animals fed high protein diets were significantly increased: theBMDof thoracic vertebrae was positively related to the CP intake (r=0.62; P < 0.001. In animals consuming higher protein diets, skeletal radiology and quantitative bone histology revealed no evidence of increased bone turnover as would be expected in animals that are in negative calcium balance. No relationship existed between limb skewness and the growth rate of lambs. However, the ratio of Ca:P in the forelimb (r = -0.98, vertebrae (r = -0.72 and rib (r = -0.42 was found to be inversely correlated with increased protein intake and resulted from an increase in the phosphorus content of bone, while the amount of bone calcium was unaffected. We conclude that qualitative micro-architectural abnormalities, and not mere bone loss, may underlie the skeletal deformities induced by increased protein consumption in sheep.

Role and mechanism of action of Sclerostin in bone

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Delgado-Calle, Jesus; Sato, Amy Y.; Bellido, Teresita

2016-01-01

After discovering that lack of Sost/sclerostin expression is the cause of the high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive animal experimentation and clinical studies demonstrated that sclerostin plays a critical role in bone homeostasis and that its deficiency or pharmacological neutralization increases bone formation. Dysregulation of sclerostin expression also underlies the pathophysiology of skeletal disorders characterized by loss of bone mass as well as the damaging effects of some cancers in bone. Thus, sclerostin has quickly become a promising molecular target for the treatment of osteoporosis and other skeletal diseases, and beneficial skeletal outcomes are observed in animal studies and clinical trials using neutralizing antibodies against sclerostin. However, the anabolic effect of blocking sclerostin decreases with time, bone mass accrual is also accompanied by anti-catabolic effects, and there is bone loss over time after therapy discontinuation. Further, the cellular source of sclerostin in the bone/bone marrow microenvironment under physiological and pathological conditions, the pathways that regulate sclerostin expression and the mechanisms by which sclerostin modulates the activity of osteocytes, osteoblasts, and osteoclasts remain unclear. In this review, we highlight the current knowledge on the regulation of Sost/sclerotin expression and its mechanism(s) of action, discuss novel observations regarding its role in signaling pathways activated by hormones and mechanical stimuli in bone, and propose future research needed to understand the full potential of therapeutic interventions that modulate Sost/sclerostin expression. PMID:27742498

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

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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.

Acute bone crises in sickle cell disease: the T1 fat-saturated sequence in differentiation of acute bone infarcts from acute osteomyelitis

International Nuclear Information System (INIS)

Jain, R.; Sawhney, S.; Rizvi, S.G.

2008-01-01

Aim: To prove the hypothesis that acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells (RBCs) in bone marrow, and to evaluate the unenhanced T1 fat-saturated (fs) sequence in the differentiation of acute bone infarction from acute osteomyelitis in patients with sickle-cell disease. Materials and methods: Two studies were undertaken: an experimental study using in-vitro packed red blood cells and normal volunteers, and a retrospective clinical study of 86 magnetic resonance imaging (MRI) studies. For the experimental study containers of packed RBCs were placed between the knees of four healthy volunteers with a saline bag under the containers as an additional control, and were scanned with the pre-contrast T1-fs sequence. Signal intensity (SI) ratios were obtained for packed RBCs:skeletal muscle and packed RBCs:saline. For the clinical study, the SIs of normal bone marrow, packed RBCs, bone and/or soft-tissue lesions, and normal skeletal muscle of 74 patients (86 MRI studies) were measured using unenhanced, T1 fat-saturated MRI. The ratios of the above SIs to normal skeletal muscle were calculated and subjected to statistical analysis. Results: Fifty-one of 86 MRI studies were included in the final analysis. The ratios of SIs for normal bone marrow, packed red cells, bone infarction, acute osteomyelitis, and soft-tissue lesions associated with bone infarct, compared with normal skeletal muscle were (mean ± SD) 0.9 ± 0.2, 2.1 ± 0.7, 1.7 ± 0.5, 1.0 ± 0.3, and 2.2 ± 0.7, respectively. The difference in the ratio of SIs of bone infarcts and osteomyelitis was significant (p = 0.003). The final diagnoses were bone infarction (n = 50), acute osteomyelitis (n = 1), and co-existent bone infarction and osteomyelitis (n = 2). Seven patients who had suspected osteomyelitis underwent image-guided aspiration. Conclusion: Acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells in the bone marrow. The

Systemic therapy of bone metastases

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Skripekova, A.

2012-01-01

Complications of bone metastases can seriously influence quality of life of the patients including of their independence in activities of daily living. Bisfosfonates are reducing skeletal morbidity in solid tumors and in multiple myeloma by 30 - 50% (1). They are not only used in active antineoplastic therapy in the prevention of skeletal complications by bone metastases but they are also significantly useful in prevention of the decrease of osseous mass by hormonal manipulation. Preclinical and in part clinical data suppose that there is some role of bisfosfonates in prevention of formation of metastases by early cancer. Denosumab is fully humanized antibody against RANKL (receptor activator of nuclear factor κ-B ligand) which is very important in pathogenesis of bone resorption induced by osteoclasts. In this work we discuss about pathological mechanisms of bone resorption in multiple myeloma and solid tumors, we resume data from randomized clinical trials and we focus on the application of anti resorption therapy in clinical practice. (author)

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

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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......-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. 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...

Aneurysmal bone cyst and other nonneoplastic conditions

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Dahlin, D.C.; McLeod, R.A.

1982-01-01

Aneurysmal bone cyst is a benign proliferative tumefaction of bone. Histologic similarities indicate a kinship among classic aneurysmal bone cysts, essentially 'solid' proliferative lesions in bones; giant cell reparative granulomas of the jaws, at the base of the skull, and in the small bones of the hands and feet; skeletal lesions of hyperparathyroidism; and even pseudosarcomatous myositis ossificans, proliferative myositis, and proliferative fasciitis. (orig.)

Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency?

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Klefter, Oliver; Feldt-Rasmussen, Ulla

2009-01-01

to a muscle modulating effect, and if treatment with GH would primarily increase muscle mass and strength with a secondary increase in BMD/BMC, thus supporting the present physiological concept that mass and strength of bones are mainly determined by dynamic loads from the skeletal muscles. METHOD: We...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...... in muscle mass occurred during the first 12 months of therapy. Most trials measuring BMD/BMC reported significant increases from baseline values. The significant increases in BMD/BMC occurred after 12-18 months of treatment, i.e. usually later than the increases in muscle parameters. Only seven trials...

Assessment of the influence of body composition on bone mass in children and adolescents based on a functional analysis of the muscle-bone relationship.

Science.gov (United States)

Golec, Joanna; Chlebna-Sokół, Danuta

2014-01-01

The functional model of skeletal development considers the mechanical factor to be the most important skeletal modulant. The aim of the study was a functional analysis of the bone-muscle relationship in children with low and normal bone mass. The study involved 149 children with low and 99 children with normal bone mass (control group). All patients underwent a densitometry examination (DXA). Low bone mass was diagnosed if the Z-score was below values of Z-scores for all parameters in children with low bone mass as compared to the control group. Children with low bone mass had lower content of adipose and muscle tissue and a marked deficit of muscle tissue with regard to height (which according to mechanostat theory leads to lower muscle-generated strain on bones). This group of children had also lower TBBMC/LBM Z-scores, which indicates greater fracture susceptibility. 1. Functional analysis, which showed associations between bone and muscle tissues, can be useful for diagnosing and monitoring skeletal system disorders as well as making therapeutic decisions.2. The study emphasizes the role of proper nutrition and physical activities, which contribute to proper body composition, in the prevention of bone mineralization disorders in childhood and adolescence. 3. The study showed the inadequacy of the classic reference ranges used in interpreting DXA data in children and demonstrated the usefulness of continuous variables for that purpose.

The Bone Marrow-Derived Stromal Cells

DEFF Research Database (Denmark)

Tencerova, Michaela; Kassem, Moustapha

2016-01-01

Bone marrow (BM) microenvironment represents an important compartment of bone that regulates bone homeostasis and the balance between bone formation and bone resorption depending on the physiological needs of the organism. Abnormalities of BM microenvironmental dynamics can lead to metabolic bone...... diseases. BM stromal cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal stem cell (BMSC)] are multipotent stem cells located within BM stroma and give rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of BMSC lineage commitment to adipocytic lineage...

Chronic alcoholism and bone remodeling processes: Caveats and considerations for the forensic anthropologist.

Science.gov (United States)

Michael, Amy R; Bengtson, Jennifer D

2016-02-01

Clinical literature provides substantial information on the effects of chronic alcohol abuse on bone remodeling and related skeletal disease processes. This biomedical information is seldom considered in detail by forensic anthropologists, who often rely on normative macroscopic models of bone remodeling and traditional macroscopic age estimation methods in the creation of biological profiles. The case study presented here considers the ways that alcoholism disrupts normal bone remodeling processes, thus skewing estimations of age-at-death. Alcoholism affects bone macroscopically, resulting in a porous appearance and an older estimation of age, while simultaneously inhibiting osteoblastic activity and resulting in a younger microscopic appearance. Forensic anthropologists must also be cognizant of pathological remodeling stemming from alcoholism in cases where trauma analysis is critical to the reconstruction of events leading up to death, as fracture healing rates can be affected. Beyond the case study, we also consider how forensic anthropologists and practitioners can recognize and account for osteological signatures of alcoholism in medico-legal contexts. In order to best estimate age at death, a combined macroscopic and microscopic approach should be employed whenever possible alcohol and drug abuse is known or suspected. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in Klinefelter syndrome

DEFF Research Database (Denmark)

Shanbhogue, Vikram V; Hansen, Stinus; Jørgensen, Niklas Rye

2014-01-01

Although the expected skeletal manifestations of testosterone deficiency in Klinefelter's syndrome (KS) are osteopenia and osteoporosis, the structural basis for this is unclear. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), microarchitecture...

Skeletal manifestations of granulocytic sarcoma (chloroma)

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Hermann, G.; Abdelwahab, I.F. (Mount Sinai Medical Center, New York, NY (United States). Dept. of Radiology); Feldman, F. (Columbia Presbyterian Medical Center, New York, NY (United States)); Klein, M.J. (Mount Sinai Medical Center, New York, NY (United States). Dept. of Pathology)

1991-10-01

Skeletal manifestations of chloroma were reviewed in five patients. In four cases, a chloroma was the initial manifestation of a systemic disease. In the fifth, an elderly patient developed a bone lesion during a blastic crisis while under treatment for chronic myelogeneous leukemia. Two patients presented with lytic lesions of the ribs, two with lytic lesions of the femur, and one with a predominantly sclerotic lesion of the scapula. The laboratory findings in two patients were within normal limits. All lesions were confirmed by bone biopsy. (orig.).

Effects of hypodynamic simulations on the skeletal system of monkeys

Science.gov (United States)

Young, D. R.; Tremor, J. W.

1977-01-01

A research and development program was undertaken to evaluate the skeletal losses of subhuman primates in hypodynamic environments. The goals of the program are: (1) to uncover the mechanisms by which weightlessness affects the skeletal system; (2) to determine the consequences and reversibility of bone mineral losses; and (3) to acquire a body of data needed to formulate an appropriate countermeasure program for the prevention of skeletal deconditioning. Space flight experiment simulation facilities are under development and will be tested for their capability in supporting certain of the requirements for these investigations.

Unexpected skeletal histology of an ichthyosaur from the Middle Jurassic of Patagonia: implications for evolution of bone microstructure among secondary aquatic tetrapods