Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone.

Bone is removed or replaced in defined locations by targeting osteoclasts and osteoblasts in response to its local history of mechanical loading. There is increasing evidence that osteocytes modulate this targeting by their apoptosis, which is associated with locally increased bone resorption. To investigate the role of osteocytes in the control of loading-related modeling or remodeling, we studied the effects on osteocyte viability of short periods of mechanical loading applied to the ulnae of rats. Loading, which produced peak compressive strains of -0.003 or -0.004, was associated with a 78% reduction in the resorption surface at the midshaft. The same loading regimen resulted in a 40% relative reduction in osteocyte apoptosis at the same site 3 days after loading compared with the contralateral side (P = 0.01). The proportion of osteocytes that were apoptotic was inversely related to the estimated local strain (P < 0.02). In contrast, a single short period of loading resulting in strains of -0.008 engendered both tissue microdamage and subsequent bone remodeling and was associated with an eightfold increase in the proportion of apoptotic osteocytes (P = 0.02) at 7 days. This increase in osteocyte apoptosis was transient and preceded both intracortical remodeling and death of half of the osteocytes (P < 0.01). The data suggest that osteocytes might use their U-shaped survival response to strain as a mechanism to influence bone remodeling. We hypothesize that this relationship reflects a causal mechanism by which osteocyte apoptosis regulates bone's structural architecture

Regulation of bone mass by mechanical loading: Microarchitecture and genetics

For decades, the processes that couple bone architecture and mass to function have been investigated and characterized. It is well known, and now well accepted, that increases in exercise and loading of bone are associated with increased bone mass, and that disuse induces osteopenia. However, the mechanisms by which disuse leads to bone loss remain poorly understood, even in the 21st century. Clearly, the skeleton is able to perceive and respond to some general input(s) generated, or lost, as a consequence of mechanical unloading of bone that are distinct from habitual activity, so called functional adaptation. It is the focus of this paper to evaluate the evidence underlying roles for genetics, osteocytes, and interstitial fluid flow in mediating disuse osteopenia.Larry J. Suva, Dana Gaddy, Daniel S. Perrien, Ruth L. Thomas and David M. Findla