Bone Abstracts

Glucocorticoids (GC) are effective drugs in the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited by negative effects on bone mass and strength, resulting in increased osteoporotic fractures. Conditional knockout mice demonstrated that the GR in osteoblasts is essential for GC-dependent bone loss. Recent studies show that GC profoundly inhibit Wnt signaling by stimulating the expression of Wnt antagonists such as dickkopf-1...

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Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that controls the engulfment of apoptotic cells and exerts anti-inflammatory effects. It has been implicated in the pathogenesis of several diseases, but its role in the bone microenvironment is still unknown. Here we tested the hypothesis that MFG-E8 also regulates bone metabolism and the development of arthritis.MFG-E8 expression was detected in mouse bones and primary murine osteobl...

Introduction: Bone metastases represent a frequent complication of breast cancer and are characterized by increased tumour-driven activation of osteoclasts and subsequent bone loss. Aminobisphosphonates inhibit osteoclast function and are established therapies of skeletal metastases. Similar to statins, they block the mevalonate pathway and are thought to have direct anti-tumour effects. Here, we report on the anti-tumour potential of a sequential inhibition of the mevalonate ...

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...

Introduction: Osteogenesis imperfecta (OI) is a genetically heterogeneous disorder characterized by bone fragility. OI type V, with autosomal dominant inheritance, is characterized by ossification of the forearm interosseus membrane, radiodense metaphyseal bands, propensity for hyperplastic callus formation, and mesh-like lamellation on bone histology. Type V OI probands are reported to have white sclerae and normal teeth. Recent reports identified the cause of type V OI as a ...

Antenatal glucocorticoid (GC) injections are not only used to enhance fetal lung maturation in preterm children but also for the treatment of maternal conditions such as autoimmune diseases or infections. Animal models and clinical studies suggest that the regulation of the hypothalamic–pituitary–adrenal axis is altered in the offspring of GC-treated mothers with increased sensitivity to stress.Objective: The aim of this study is i) to define t...