Bone Abstracts

Twelve different mutations in TNFRSF11A (encoding the RANK receptor) have been associated with osteoclast-poor autosomal recessive osteopetrosis in patients. Two truncated RANK proteins resulting from substitution mutations (W434X and G280X), identified in two infants, cause loss of the intracellular oligomerisation motif and in the case of the G280X mutation the TRAF6 binding domain. A third mutation was identified in a 10-year-old patient and is a frameshift mutatio...

Aims: To describe different multinucleated giant cell phenotypes and their associations with synovitis in people with rheumatoid arthritis (RA) or osteoarthritis (OA), and in an experimental model of chronic arthritis.Material and methods: A cross-sectional comparative study was performed on samples of knee synovia from age-matched patients with RA, OA, or non-arthritic post mortem (PM) controls. OA synovia were stratified by histological inflammation gr...

Chronic obstructive pulmonary disease (COPD) has been found associated with low areal bone mineral density and an increase in fracture rate. Previous histomorphometric findings revealed abnormally low cancellous bone volume and thin cortices. In the present work, we studied the same transiliac bone biopsy samples from n=19 COPD patients for cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) based on quantitative backscatter electron im...

Background: Magnetic resonance imaging (MRI) is used clinically to assess bone marrow, muscle and joints. The assessment of cortical and trabecular structure using MRI may provide further insight into the muscle–bone–bone marrow unit. Previous studies using MRI to evaluate microarchitecture are confined to research due to the need for specially adapted coils and navigator software to limit motion artifact. We present a novel statistical method using HRpQCT to determi...

Introduction: Bisphosphonate treatment in children with osteogenesis imperfecta reduces bone catabolism and relies on modelling to form new bone. An anabolic treatment, anti-sclerostin antibody (Anti-SOST Ab), is being investigated in clinical trials. We hypothesized that combined treatment may produce superior outcomes in OI.Methods: Female Col1a2 G610C mice and their wild type littermates (WT) were treated from week 5 to week 9 of life with either sali...

Fractures in infancy raise the spectre of child abuse; it has been suggested that lack of vitamin D could result in bone abnormalities that could predispose to fractures. We utilised a mouse model system to investigate whether vitamin D deficiency in utero alters early bone growth and development.C57BL/6 female mice received vitamin D deficient or replete diet for 6 weeks, then mated and continued on their respective diets until weaning. Pups were culled...

Objective: Bone metabolism was studied in patients with phosphate diabetes before and after medication.Methods: 39 patients with phosphate diabetes age 2–18 years (7.8±4 years, 64% male) and multiplanar deformities of the lower extremities were treated with monthly vitamin D (2000 IU/day), alfacalcidol (0.25 mg/every other day) and calcium glycerophosphate (600 mg/day) for 6 months.Biochemical indices were evaluated befor...

Cancer-associated muscle weakness is an important paraneoplastic syndrome for which there is currently no treatment. Human breast cancer bone metastases (MDA-MB-231 cells in immune deficient mice) induce extensive bone destruction, leading to the release of TGF-β from the bone matrix. We have previously shown that bone-derived TGF-β is responsible for muscle weakness in this model. Mechanistically, TGF-β signaling increases the expression of NADPH oxidase 4 (Nox...

Up to half of women treated with an aromatase inhibitor (AI) for breast cancer develop muscle weakness, bone loss, and joint pain. Moreover, an elevated state of osteoclastic bone resorption has been shown to prime the bone microenvironment in ways that accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Four-week female athymic nude mice underwe...

Loss of the gene encoding the secreted Wnt antagonist sclerostin results in increased bone mass in humans and mice. Administration of antibodies to sclerostin (Scl-Ab) has been shown to increase bone mineral density (BMD) by increasing bone formation and decreasing bone resorption, in both animal studies and human clinical trials. In these studies, the magnitude and rate of increase in bone formation markers, and the rate of increase of BMD, diminishes upon repeat dosing with ...