3D simulation of remodeling at the level of the cell and its deregulation in disuse

A load-adaptive bone remodeling theory is used to simulate remodeling at the level of the cell in threedimensional models. It was found that the theory can successfully explain the formation of hemi-osteons in trabecular bone and full osteons in cortical bone and their deregulation after disuse. Introduction: Osteoporosis can occur as the result of mechanical disuse. In recent studies, we developed a remodeling theory that explains bone remodeling at the level of the cell as the result of changes in local mechanical loading that is sensed by osteocytes which then regulate osteoblast and osteoclast activity. Using two-dimensional computer simulation modeling, we demonstrated that this theory can explain the coupling between osteoclast and osteoblast cells, the formation of trabeculae and cortical osteons, and their adaptation to changes in mechanical loading. The goal of the present study was to extend the modeling to three dimensions and to investigate if it can explain the three-dimensional direction of resorption and the coupling of formation as well as the effects of disuse at the level of the cell. Methods: Finite element analysis is used to calculate the local mechanical strains resulting from external loads acting on the bone structure that either represents a single trabeculae or a cortical osteon. Osteocytes within the bone are modeled to sense mechanical loading and emit a signal. This signal inhibits attachment of osteoclasts, which are explicitly represented using a cell simulation model, and stimulates bone formation by osteoblasts. Osteon development was simulated starting from an initial resorption cavity, first for normal and second for 25% reduced loading conditions. Results: In the cortical volume, cylindrical osteons aligned to the principal loading direction developed. In the modeled trabecula, osteoclasts moved along the surface, creating hemi-osteons. In both situations, a clear coupling between osteoclast and osteoblast activity was found. Reducing the load resulted in increased osteon diameter in cortical bone and perforation of the trabecula. Discussion: The model successfully captured typical bone remodeling characteristics at the level of the cell as a result of the strain-induced osteocyte signaling theory. Changes in remodeling after simulation of disuse concur with observations reported in the literature.