Abstract
Bones are thought to become fragile with advancing age due to a loss of mass and structure. However, there are important aspects of bone fragility and fracture that cannot be explained simply by a loss of bone: 30% of all patients told they have healthy bone based on bone mineral density (BMD) measurements go on to fracture.
It has been suggested that increased fracture risk might also be due to ageing at the nanoscale, which might deteriorate the overall mechanical properties of a bone. However, it is not clear how mechanics at the level of the collagen-mineral matrix relate to mechanical properties of the whole bone, or whether nano-mechanics contribute to fracture risk. In order to answer these questions our group is developing state of the art methods for analysing the structure and function of the collagen mineral matrix under loading.
To image the collagen mineral matrix we obtained beam time on a synchrotron particle accelerator at the Diamond Light Source (Didcot, UK). Electrons are accelerated to near light speed by powerful electromagnets, then slowed to create high energy monochromatic X-Ray beams. Through a combination of X-Ray computed tomography and X-Ray diffraction we have been able to image the collagen/mineral matrix. Furthermore, using in situ loading experiments it has been possible to visualise collagen fibrillar sliding and mineral crystal structure.
Our group is analysing how age related changes in nano-structure affect bone mechanical behaviour. As well as comparing fragility fracture patients with ‘healthy’ age matched controls to investigate whether ageing at the nano-scale could increase fracture risk. We are also assessing the effect of common treatments for bone fragility (e.g. bisphosphonate) on nano-mechanics.
Unfortunately the expense and high radiation dose associated with synchrotron imaging prevents the technology from being adapted for patients. Therefore the next step will be to identify and test tools that can be used to indirectly assess bone chemistry and mechanical properties at point of care (e.g. laser spectroscopy and indentation). The data could be used to improve the diagnosis, monitoring and treatment of bone fragility.
