Abstract

The process of bone remodeling is carried out by ‘basic multicellular units’ of osteoclasts and osteoblasts. Osteoclasts excavate a resorption space that is subsequently filled with new bone by osteoblasts. In cortical bone osteoclasts dig tunnels through solid bone, in cancellous bone they dig trenches across the trabecular surface. Osteoblasts fill these tunnels and trenches, creating osteons and hemi-osteons, respectively. Both the osteons of cortical bone and the trabeculae of cancellous bone are aligned to the dominant loading direction, indicating that BMU's are mechanically regulated. How mechanical forces guide these cells is still uncertain. We hypothesize that strain-induced osteocyte signals inhibit osteoclast activity and stimulate osteoblast activity. This hypothesis was implemented in a finite element-based bone adaptation model, that was extended with a cell simulation model. This allowed us to examine tunneling and trenching by osteoclasts. We found that our simulations capture key features of BMU-based remodeling: (1) cortical BMU's create load-aligned osteons; (2) cancellous BMU's move across the surface of trabeculae instead of piercing them; (3) resorption–formation coupling occurs in response to strains around resorption sites; and (4) resorbing osteoclasts target nearby regions of osteocyte death, thus providing a mechanism for bone repair.

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