Bone Abstracts

Peripheral quantitative computed tomography (pQCT) is receiving considerable attention in the diagnosis and monitoring of human bone diseases. It is well accepted that lower image resolution compared to micro-computed tomography (micro-CT) affects bone morphometry. With advances in micro-CT evaluation techniques such as sample-specific remodeling simulations or dynamic bone morphometry, there is the potential to also allow the application of such techniques to clinical pQCT sc...

Bone strength, hence fracture risk, is dependent on bone geometry, microstructure and bone material level properties. We have reported that microstructure and material level properties contribute independently to the increase in bone strength in rats treated with strontium ranelate for 2 years, as evaluated by μCT-based Finite Element analysis.We investigated the effects of strontium ranelate (SrRan) treatment on bone material level properties of tr...

Bone microarchitecture and material level properties independently contribute to the improvement of bone strength induced by strontium (Sr) ranelate treatment as evaluated by μCT-based finite element analysis. The influence of in vitro Sr exposure on material level properties and on bone mechanical properties is unknown.We investigated whether in vitro exposure of rat femurs to Sr is able to modify the bone mechanical properties in...

A micro-indentation technology potentially allows in vivo investigation of intrinsic bone tissue quality, a determinant of bone fragility. Thus the signification of the parameters investigated is still unclear.Since protein malnutrition affects bone material level properties – geometry and strength – rats were fed a normal or an isocaloric low-protein diet. Both femurs were collected and measurements of geometry using micro CT, materia...

Subchondral bone remodelling and osteophyte growth are widely recognised hallmarks of knee osteoarthritis (OA) although their contribution to disease is not fully understood. Murine models, with targeted genetic modifications, have become powerful tools for discovering disease pathophysiology. Our unpublished observations suggest that osteophyte formation is independent of cartilage loss thereby implying potentially independent molecular drivers. We have developed a novel imag...

Adaptive responses of the skeleton to loading changes architecture and physical properties in order to optimise strength for function. However, bone is subjected to many local and circulating osteotropic factors, most acting on G-protein coupled receptors. Receptor activity modifying protein-3 is a single trans-membrane domain receptor accessory protein, which aids in trafficking of calcitonin and calcitonin-like receptors to the cell surface and changes ligand selectivity. As...

Glucocorticoids inhibit osteoblast function and cause an increase in osteoblast and osteocyte apoptosis. Bone remodelling defects occur resulting in an increase in fracture risk that cannot be fully explained by decreases in bone mineral density (BMD). We propose that this may be due to alterations in bone quality. Trabecular bone score (TBS) correlates with 3D bone micro-architectural parameters and can be derived directly from grey-level variations within 2D DXA images.<...

Mammalian target of rapamycin (mTOR) is a serine–threonine kinase that plays a central role in a number of key cellular pathways that have been previously implicated in bone formation. mTOR mediates these diverse roles by forming two multi-protein complexes, mTORC1 and mTORC2, each of which is defined by unique proteins raptor and rictor respectively.Studies from our laboratory have previously demonstrated that inhibition of mTORC1 increases the ost...

Neurofibromatosis type 1 (NF1) is a genetic disorder with an incidence of 1/3000. Inactivating mutations in the NF1 gene cause Ras-MEK overstimulation, and predisposes NF1 patients to cancer. A new generation of MEK inhibitors (PD0325901 and AZD6244) are under clinical trials in cancer patients, including NF1 patients. Congenital pseudarthrosis of the tibia is a major complication for NF1 patients, and associates with loss-of-heterozygosity of the NF1 gene. The primary aim of ...

The switch from a cartilage template to bone during endochondralossification of the growth plate requires dynamic and close interaction between the cartilage and the developing vascular structures. Vascular invasion of hypertrophic cartilage, with blood vessels coming from the bone collar, serves to bring in osteoblast- andendothelial precursor cells along with chondroclasts and their precursors into future ossification centres of the growth plate.Potent...