Devising accurate techniques to understand mechanisms of increased fragility in metabolic bone diseases like osteoporosis is a critically important need. Osteoporosis affects over 3 million people in the UK – it is the leading cause of hospital admission for women over 50. Current diagnostic techniques like dual X-ray absorptiometry (DXA), which measure the changes in bone quantity (bone mineral areal density or BMD) cannot fully account for the increased fracture risk in osteoporotic patients. Likewise, the reduced fracture risk after treatment with drugs like bisphosphonates cannot be fully explained by changes in BMD alone.

In this project we develop novel synchrotron-based X-ray nanomechanical imaging techniques capable of assessing fracture-enhancing changes in bone quality (as distinct from bone quantity), and test its effectiveness by applying it to a range of bone disorders developed in mouse models developed by ENU mutagenesis. The disorders include glucocorticoid induced osteoporosis, premature ageing, osteoarthritis, and structural changes in bone associated with obesity.


Using high brilliance synchrotron X-rays to carry out time-resolved small-angle X-ray scattering and wide-angle X-ray diffraction on bone biopsies during in situ mechanical loading, we measure the nanoscale fibrillar and mineral strain in the bone matrix during the application of external stresses. These measurements provide previously inaccessible information on disease-induced changes in the nanomechanical competence of bone, which may lead to fragility fractures. By establishing SAXD-MT in this preclinical project on mouse models, we will enable its future application - in conjunction with wider field imaging modalities - in improving the diagnosis of fracture-enhancing changes in human cohorts. This project is in collaboration with the Medical Research Council (Harwell, UK), the Oxford Centre for Clinical Endocrinology and Metabolism (OCDEM) at the Nuffield Department of Medicine, University of Oxford, and Diamond Light Source (DLS), UK’s primary synchrotron source.

References

[1] A. Karunaratne et al, Bone (2013)
[2] A. Karunaratne et al, Bone (2012)
[3] A. Karunaratne et al, J. Bone Miner. Res. (2012)
[4] J. Seto et al, PLoS One (2012)
[5] C. Esapa et al, J. Bone Miner. Res. (2012)