Toward a unifying theory of bone remodeling.

A theory is developed to resolve several inconsistencies between current concepts and observations about bone remodeling. For example, the observation that remodeling increases both when mechanical loading is excessively low, that is, in a disuse state, and when it is excessively high, producing substantial fatigue damage, is contrary to the widely held assumption that a signal generated by osteocytes in proportion to mechanical loading stimulates bone lining cells to activate remodeling. The new theory resolves this disparity by assuming that lining cells are inclined to activate remodeling unless restrained by an inhibitory signal, and that the mechanically provoked osteocytic signal serves this inhibitory function. Consequently, remodeling is elevated when signal generation declines due to reduced loading, or when signal generation or transmission is interrupted by damage due to excessive loading. Otherwise, remodeling is kept at a relatively low level by inhibitory signals produced through physiologic loading. Furthermore, the inhibitory signal is postulated to be identical to that proposed by Marotti as the mechanism for conversion of osteoblasts to osteocytes, and responsible for the diminishment of apposition rate during refilling of osteonal basic multicellular units. Consequently, a single, mechanically derived signal, produced in the osteocytic syncytium, may control osteoblast and bone lining cell functions, and thereby a variety of important phenomena in bone biology.