Postmenopausal osteoporosis as a failure of bone's adaptation to functional loading: a hypothesis.

There is substantial evidence that bones' ability to withstand functional loading without damage depends on the processes of bone modeling and remodeling, which are responsible for establishing and maintaining bone architecture, being influenced by a feedback mechanism related to the control of functional strains. It is probably useful to consider the diminished ability to maintain bone strength in postmenopausal osteoporosis as a failure of this mechanism. Acceptance of this approach would not only increase understanding of the etiology of postmenopausal osteoporosis but also significantly influence the ways in which it is investigated and treated. This would not mean that the many other factors affecting bone mass and bone cell activity will be ignored, but rather these factors will be put in perspective. Research to prevent or treat osteoporosis could be directed usefully to understanding how osteoblasts, lining cells, and osteocytes respond to mechanically derived information and how these responses are converted into stimuli controlling structurally appropriate modeling and remodeling. Evidence suggesting that early strain-related responses of bone cells in males and females involve the estrogen receptor (ER) could explain decreased effectiveness of this pathway when ER levels are low.