Bone Abstracts

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The G protein-coupled receptor, protease-activated receptor 2 (PAR2), is expressed by osteoblasts and required for normal skeletal growth and repair. Prostate cancer (PCa) cells commonly secrete proteolytic activators of PAR2 (including matriptase and kallikrein-related peptidase 4) and frequently form osteogenic metastases in bone. This study was undertaken to investigate the hypothesis that PAR2 activators released by PCa cells modulate osteo...

Bisphosphonates (BPs) such as zoledronic acid (ZA) are widely used to treat bone diseases. The use of BPs can lead to osteonecrosis of the jaw (ONJ), but it is not clear why in particular the jaw bone is affected. Previously, it was shown that osteoclasts derived from different bone sites have different properties. We hypothesize that BPs have distinct effects on bone-site specific osteoclasts or precursors. To investigate this, female C57BL/6J mice were injected intraperitone...

Introduction: Dentinogenesis imperfecta (DI) is a common dental aberration in patients with osteogenesis imperfecta (OI). Mutations that cause abnormal collagen chains will cause more serious types of OI and it has been claimed that DI should be a marker for qualitative defected collagen. It has also been supposed that normal development of teeth may be more dependent on normal α2(I) than normal α1(I) chains which are encoded by COLIA2 and COLIA1 ge...

Denosumab (DMAb) significantly improves bone strength at the hip, estimated by FEA from QCT scans, from baseline (B/L) and vs placebo (Pbo) (Keaveny ASBMR 2010). We determined the extent and distribution of mass and thickness changes at the proximal femur, a key skeletal site for fracture risk, using a novel cortical bone mapping technique on the same serial QCT scans. A FREEDOM substudy included 80 women who underwent hip QCT scanning at B/L and months 12, 24 and 36 during DM...

Brittle bones have been reported in children, adolescents and adults with cystic fibrosis (CF), independently of sex; this has been termed CF-related bone disease. In CF patients with the F508del mutation in the (Cftr) gene, vertebral fractures and the subsequent dorsal kyphosis decrease pulmonary function, thus accelerating the course of the disease. Mice with the homozygous F508del mutation in CFTR develop a severe osteopenic phenotype early on, in both sexes (Le He...

Turner syndrome (TS) is known to be associated with increased risk of osteoporosis and fracture. Childhood treatment with GH has been considered standard of care for treatment of growth failure in TS, while the influence of GH on bone health has been poorly understood. The purpose of this study is to assess the influence of GH on bone microarchitecture on a cohort of TS subjects.TS subjects aged 16–45 were included. Bone mineral density (BMD) was as...

Fractures are very common and affect 2% of the population per annum. Fragility fractures represent the greatest unmet need and are associated with high rates of morbidity and mortality. Currently, there is no approved therapy for enhancing healing of fragility fractures. We previously reported that upregulation of the early inflammatory response following skeletal injury can promote fracture repair (Glass et al PNAS 2011). Inflammation represents the earliest response followin...

Background: Osteoclasts are unique multinucleated cells that originate from the fusion of monocytes. They are the only cells known to be capable of bone resorption. Interestingly, the foreign body multinucleated giant cell (FBGC) arises from the same lineage as the osteoclast, and they share numerous similar characteristics, among which the expression of tartrate resistant acid phosphatase (TRAcP). Yet, it is not known whether the FBGC has the capacity to resorb bone.<p cl...