A whole bone-lacunocanalicular network-osteocyte model examining bone adaptation to distinct loading parameters

The mechanical adaptive responses of bone are affected by various parameters of the loading, such as magnitude, rate, frequency, number of cycles, and recovery time. However, the precise relationships between different loading parameters and bone adaptation as well as their governing mechanism remain unclear. Here, we developed a novel multi-scale model of whole bone-lacunocanalicular network (LCN)-osteocyte characterizing whole-bone deformation-produced fluid flow within a large LCN as well as responses of osteocytes to fluid shear stress (FSS) via opening, closing, or inactivating mechanosensitive ion channels (MSIC). The model was next used to examine the effects of loading magnitude, frequency, cycle numbers, and recovery time on the responses of osteocytes. Results showed that the load magnitude and frequency mainly affected the proportion of open MSIC by changing FSS on the osteocytes. When the load-induced FSS increased, the proportion of open osteocyte MSIC was enhanced. With an increase in the cycle number, MSIC transformed gradually from an open state into an inactivated state, resulting in saturation in response to continuous FSS. Interestingly, a short-term recovery time restored the MSIC to a closed state which could turn into an open state following subsequent loading, while a long-term recovery time was helpful for recovering the mechanical sensitivity of the osteocytes. These computational results largely replicated the mechanical responses of bone as observed in in vivo animal loading experiments, suggesting the importance of osteocyte MSIC in response to different loading parameters. This multi-scale model considering osteocyte MSIC could provide mechanistic insights into bone adaptation to distinct mechanical stimuli.