An analytical approach to investigate the evolution of bone volume fraction in bone remodeling simulation at the tissue and cell level.

Simulation of bone remodeling at the bone cell level can predict changes in bone microarchitecture and density due to bone diseases and drug treatment. Their clinical application, however, is limited since bone microarchitecture can only be measured in the peripheral skeleton of patients and since the simulations are very time consuming. To overcome these issues, we have developed an analytical model to predict bone density adaptation at the organ level, in agreement with our earlier developed bone remodeling theory at the cellular level. Assuming a generalized geometrical model at the microlevel, the original theory was reformulated into an analytical equation that describes the evolution of bone density as a function of parameters that describe cell activity, mechanotransduction and mechanical loading. It was found that this analytical model can predict changes in bone density due to changes in these cell-level parameters that are in good agreement with those predicted by the earlier numerical model that implemented a detailed micro-finite element (FE) model to represent the bone architecture and loading, at only a fraction of the computational costs. The good agreement between analytical and numerical density evolutions indicates that the analytical model presented in this study can predict well bone functional adaptation and, eventually, provide an efficient tool for simulating patient-specific bone remodeling and for better prognosis of bone fracture risk.