La regulación mecánica de la estructura ósea: estudio multidisciplinario Translated title: Mechanical regulation of bone structure: a multidisciplinary stud

Osteocytes, the most abundant cells in bone, have been long postulated to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts. The discovery that the inhibitor of bone formation sclerostin is primarily expressed in osteocytes in bone and downregulated by anabolic stimuli provided a mechanism by which osteocytes influence the activity of osteoblasts. Advances of the last few years provided experimental evidence demonstrating that osteocytes also participate in the recruitment of osteoclasts and the initiation of bone remodeling. Apoptotic osteocytes trigger yet-to-be-identified signals that attract osteoclast precursors to specific areas of bone, which in turn differentiate to mature, bone-resorbing osteoclasts. Osteocytes are also the source of molecules that regulate the generation and activity of osteoclasts, such as OPG and RANKL; and genetic manipulations of the mouse genome leading to loss or gain of function or to altered expression of either molecule in osteocytes markedly affect bone resorption. This review highlights these investigations and discusses how the novel concept of osteocyte-driven bone resorption and formation impacts our understanding of the mechanisms by which current therapies control bone remodeling.

In former views hormones, calcium, vitamin D and other humoral and nonmechanical agents dominated control of postnatal bone strength (and "mass") in children and adolescents. However later evidence that led to the Utah paradigm of skeletal physiology revealed that this control depends strongly on the largest mechanical loads on bones. Trauma excepted, muscles cause the largest loads and the largest bone strains, and these strains help to control the biological mechanisms that determine whole-bone strength. That makes the strength of children's load-bearing bones depend strongly on growing muscle strength and how bones respond to it. Most hormones and other nonmechanical agents that affect bone strength can help or hinder that "bone strength-muscle strength" relationship but cannot replace it. In addition some agents long thought to exert bone effects by acting directly on bone cells, affect muscle strength too. In that way they could affect bone strength indirectly. Such agents include growth hormone, adrenalcorticosteroid analogs, androgens, calcium, genes, vitamin D and its metabolites, etc. Thus bone and muscle do form a kind of operational unit. It is part of the Utah paradigm that supplements earlier views with later evidence and concepts. The paradigm explains how the "bone strength-muscle strength" relationship works. This article provides an overview of that physiology, and some of its implications for pediatric endocrinologists.