The osteocyte as an orchestrator of bone remodeling: an engineer’s perspective

Bone is adapted to mechanical loading. The trabeculae in cancellous bone and the osteons in cortical bone are aligned to the mechanical loading direction. Our bones are constantly remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts, cooperating in so-called basic multicellular units or BMUs. In cortical bone, osteoclasts dig tunnels through solid bone, while in cancellous bone, they dig trenches across the trabecular surface. Osteoblasts fill these tunnels and trenches, creating osteons and hemi-osteons, respectively. How mechanical forces guide these cells is still uncertain, but mechanosensitive osteocytes are believed to orchestrate bone remodeling by sending signals to the cells at the bone surface. Computer simulations have demonstrated that local remodeling regulated by mechanosensitive osteocytes indeed produces load-aligned trabeculae and osteons. The strains around a BMU resorption cavity are concentrated at the lateral sides, away from the loading axis. Strain-induced osteocyte signals from these regions likely repel osteoclasts, forcing them to resorb bone in the loading direction, and at the same time, such signals could recruit osteoblasts to start bone formation. Thus, mechanosensitive osteocytes likely regulate the steering of and coupling within BMUs. A region of osteocyte death (therefore, lacking osteoclast-repelling signals) near the path of the BMU redirects its course to resorb this region. This may provide a mechanism for damage removal, because osteocyte death is associated with microdamage. BMUs may also function with disuse-induced osteocyte signals that recruit osteoclasts to the relatively unloaded region in front of the BMU and inhibit osteoblastic bone formation by osteoblast-inhibiting signals such as sclerostin when the tunnel or trench is sufficiently filled.