Predicting cortical bone resorption in the mouse tibia under disuse conditions caused by transient muscle paralysis

Load removal from the load-bearing bone, such as during extended space travel or prolonged bed rest, negatively affects bone health and leads to significant bone loss. However, the underlying principle that relates the bone loss to the lack of physiological loading is poorly understood. This work develops a mathematical model that predicts cortical bone loss at three sections along the length of a mouse tibia: distal, mid-section, and proximal. Dissipation energy density induced by loading, based on interstitial fluid flow, has been adopted as the mechanotransduction-triggering stimulus. The developed model uses the loss of stimulus due to the disuse of bone as an input and predicts the quantity of bone loss with spatial accuracy. It is hypothesized that the bone loss would occur at the site of maximum stimulus loss due to disuse. To test the hypothesis, stimulus loss was calculated, i.e., loss of dissipation energy density due to bone disuse, through poroelastic analysis using the finite element method. A novel mathematical model has been developed, successfully relating this loss of stimulus to the in vivo bone loss data in the literature. As per the model, the site-specific mineral resorption rate is shown to be proportional to the square-root of the loss of dissipation energy density. To the best of the authors' knowledge, this model is the first of its kind to compute site-specific bone loss. The developed model can be extended to predict bone loss due to other disuse conditions, such as long space travel and prolonged bed rest.