Toward a unifying theory of bone remodeling

A theory is developed to resolve several inconsistencies between current co ncepts 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 sub stantial fatigue damage, is contrary to the widely held assumption that a s ignal generated by osteocytes in proportion to mechanical loading stimulate s bone lining cells to activate remodeling. The new theory resolves this di sparity by assuming that lining cells are inclined to activate remodeling u nless restrained by an inhibitory signal, and that the mechanically provoke d osteocytic signal serves this inhibitory function. Consequently, remodeli ng is elevated when signal generation declines due to reduced loading, or w hen signal generation or transmission is interrupted by damage due to exces sive loading. Otherwise, remodeling is kept at a relatively low level by in hibitory signals produced through physiologic loading. Furthermore, the inh ibitory 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 linin g cell functions, and thereby a variety of important phenomena in bone biol ogy. (C) 2000 by Elsevier Science Inc. All rights reserved.