Bone Abstracts

Objectives: Bone, muscle and fat share common mesenchymal origins yet current methods separately examine lean, fat and/or bone content. We hypothesized specific musculoskeletal phenotypes derived from relative contributions of each tissue.Methods: Design: We obtained information from the 6-year follow-up of mother–offspring pairs within the Southampton Women’s Survey, a prospective population-based cohort study of 12 583 initially non-pregnant ...

Background: Hypercalcaemia is a risk following stem cell transplant (SCT) for all types of autosomal recessive osteopetrosis (ARO) due to restored osteoclast differentiation. This can be particularly severe in the osteoclast-poor (OP) form involving the tumour necrosis factor receptor superfamily 11A (TNFRSF11A) gene, encoding RANK. Denosumab, a monoclonal antibody blocking RANK activation, has been described for refractory post-SCT hypercalcaemia in two cases. Our case adds n...

Biographical DetailsKen White, PhD is the David D Weaver Professor of Genetics in the Department of Medical and Molecular Genetics at the Indiana University School of Medicine in Indianapolis, IN, USA. He serves as Director of the Division of Molecular Genetics and Gene Therapy. Dr K White’s research interests focus on the molecular genetics of metabolic bone diseases in regards to p...

Introduction: Activated protein C (APC) plays an important role in the cutaneous healing of chronic wounds arising from orthopaedic surgery and has cytoprotective and anti-inflammatory properties which may also assist bone repair. The aim of this study was to examine whether APC could directly influence osteoblasts and increase bone formation in a rodent model.Methods: Proliferation of MG-63 osteoblast-like cells was quantified by MTT assay and direct co...

Osteoclast resorption depends on their ability to reorganise their actin cytoskeleton and form the sealing zone. In order to resorb bone, osteoclasts become polarised by condensing their podosomes into a highly dynamic podosomal belt. The podosome turnover is regulated by several factors such as non-receptor tyrosine kinases, small GTPases and actin-binding proteins. The innate immune system responds to viral pathogens. Cytoplasmic double-stranded DNA activates the immune syst...

Since the identification of LRP5 as the causative gene for the osteoporosis pseudoglioma syndrome (OPPG) as well as the high bone mass (HBM) phenotype, LRP5 and the Wnt/β-catenin signalling have been extensively studied for their role in the differentiation and proliferation of osteoblasts, in the apoptosis of osteoblasts and osteocytes and in the response of bone to mechanical loading. However, more recently the direct effect of LRP5 on osteoblasts and bone formation has...

The musculoskeletal system experiences severe mechanical strain, with repetitive or extreme strains causing significant trauma; the result being an increase in mechanobiological studies evaluating mechanical strain on musculoskeletal cells. Currently, most stretching studies utilise fibronectin-coated cultures, as these enhance cell attachment. However, recent studies suggest that fibronectin increases cell turnover and DNA damage and affects cell differentiation. Furthermore,...

Osteoclast-poor autosomal recessive osteopetrosis is characterised by susceptibility to fracture despite high bone mineral density as a consequence of an absence of osteoclasts. One of the 12 receptor activator of NF-κB (RANK) mutations associated with this condition is a frameshift mutation encoding a protein that is truncated within the extracellular, N-terminal domain (R110Pfs). We investigated the effect of this mutation on osteoclast formation, receptor localisation ...

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 ...

Shwachman Diamond syndrome (SDS; MIM 260400) is a monogenic, autosomal recessive, pancreatic condition often accompanied by low bone mass and fracture. In SDS, as in cystic fibrosis, a low bone mass may be secondary to poor nutrition or chronic low-grade infection, but it has also been suggested there may be a primary bone phenotype. Paradoxically, recent studies in cell lines and in a mouse knockout for the SBDS gene, have suggested changes in important osteoclast gr...