Multiscale investigation of the functional properties of the human femur.

The mechanical strength of human bones has often been investigated in the past. Bone failure is related to musculoskeletal loading, tissue properties, bone metabolism, etc. This is intrinsically a multiscale problem. However, organ-level performance in most cases is investigated as a separate problem, incorporating only part (if any) of the information available at a higher scale (body level) or at a lower one (tissue level, cell level). A multiscale approach is proposed, where models available at different levels are integrated. A middle-out strategy is taken: the main model to be investigated is at the organ level. The organ-level model incorporates as an input the outputs from the body-level (musculoskeletal loads), tissue-level (constitutive equations) and cell-level models (bone remodelling). In this paper, this approach is exemplified by a clinically relevant application: fractures of the proximal femur. We report how a finite-element model of the femur (organ level) becomes part of a multiscale model. A significant effort is related to model validation: a number of experiments were designed to quantify the model's sensitivity and accuracy. When possible, the clinical accuracy and the clinical impact of a model should be assessed. Whereas a large amount of information is available at all scales, only organ-level models are really mature in this perspective. More work is needed in the future to integrate all levels fully, while following a sound scientific method to assess the relevance and validity of such an integrated model.