IBMS BoneKEy | Perspective
Regulation of bone mass: Local control or systemic influence or both?
Lance E Lanyon
Toshihiro Sugiyama
Joanna S Price
DOI:10.1138/20090382
Abstract
Bone mass and architecture are primarily of importance in relation to load-bearing. Despite this it is common to ascribe the role of “regulator of bone mass” to practically any substance that influences bone cell activity. Here we argue that “regulation” of bone mass and architecture, as a process to achieve particular local structural objectives, should be distinguished from “influence” arising from effects on (re)modeling derived from local, systemic or centrally-derived factors that are uninfluenced (often uninfluencible) by the architectural outcome. The mechanisms involved in structural regulation of bone mass and architecture in relation to functional loading are commonly termed the “mechanostat.” Its controlling input is assumed to be the mechanical strains engendered within the tissue by customary loading. Even in its initial stages during which strains are transduced into biochemical responses the mechanostat does not appear to employ a unique signaling pathway; instead it shares a number of pathways used by local or systemic influences that have no feedback directly related to any particular bone mass or architecture. Through the effect of these interactions the initial assessment of strain, as well as the early responses to it, are sensitive to context. The effect of different contexts such as high or low estrogen or PTH can diminish, complement or synergize with the consequences of strain-related stimulation. At extreme levels the effect of context may mask the consequences of strain completely. Strategies for therapeutic intervention to achieve structurally beneficial effects on bone (re)modeling should therefore be designed to synergize, rather than to compete, with the mechanisms of the mechanostat.
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