Structural and material changes of human cortical bone with age : Lessons from the Melbourne femur research collection

Age-related bone diseases, such as osteoporosis (OP), have a detrimental impact on individuals and society. One in ten people who suffer an osteoporotic hip fracture will die soon after the event, and at least a further 50% will suffer from chronic debility and deterioration in their quality of life. The cost of hip fractures to the Australian community (a relatively small population of only 24million people) was estimated at AUD 600 million in 2017 and the situation continues to get rapidly worse as the population ages. In order to address this problem bone research has pursued several avenues to better understand age-related changes of the skeleton and the effects of therapeutic interventions. Advances in imaging technologies combined with computational modeling has the potential to provide new insights into disease etiology and predicting effects of various therapeutic interventions. While longitudinal dual X-ray absorptiometry (DXA) imaging has been the gold standard for assessment of OP and effectiveness of drug treatments, it does not provide detailed three-dimensional information on structural morphology and material properties. Significant progress of current understanding of age-related changes in cortical bone has been made using cross-sectional studies, analyzing human post-mortem femoral specimen. Particularly, the Melbourne Femur Research Collection (MFRC), a collection of > 600 human femoral samples including males and females from across the lifespan (20-95 years). This collection is one of the most comprehensive collections currently available representing a contemporary, economically developed Western society. The MFRC has also acted as a catalyst for many research collaborations in the bone field across the world. This article first reviews how the MFRC was originally established and summarizes past and current collaborations. Secondly, we provide a summary on findings of structural changes of cortical bone with age with emphasis on changes in vascular porosity and bone specific surface. Thirdly, we provide an overview on changes in material properties with age with focus on spatial and temporal changes of bone tissue mineral density. Finally, we provide a summary and outlook of latest in-vivo imaging techniques which may pave the way to a more holistic understanding of age-related bone diseases and how to access the MFRC for future research.