Multiscale modelling and nonlinear finite element analysis as clinical tools for the assessment of fracture risk.

The risk of osteoporotic fractures is currently estimated based on an assessment of bone mass as measured by dual-energy X-ray absorptiometry. However, patient-specific finite element (FE) simulations that include information from multiple scales have the potential to allow more accurate prognosis. In the past, FE models of bone were limited either in resolution or to the linearization of the mechanical behaviour. Now, nonlinear, high-resolution simulations including the bone microstructure have been made possible by recent advances in simulation methods, computer infrastructure and imaging, allowing the implementation of multiscale modelling schemes. For example, the mechanical loads generated in the musculoskeletal system define the boundary conditions for organ-level, continuum-based FE models, whose nonlinear material properties are derived from microstructural information. Similarly microstructure models include tissue-level information such as the dynamic behaviour of collagen by modifying the model's constitutive law. This multiscale approach to modelling the mechanics of bone allows a more accurate characterization of bone fracture behaviour. Furthermore, such models could also include the effects of ageing, osteoporosis and drug treatment. Here we present the current state of the art for multiscale modelling and assess its potential to better predict an individual's risk of fracture in a clinical setting.