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

There is substantial evidence that bones' ability to withstand functional l oading without damage depends on the processes of bone modeling and remodel ing, which are responsible for establishing and maintaining bone architectu re, being influenced by a feedback mechanism related to the control of func tional 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 understandi ng of the etiology of Postmenopausal osteoporosis but also significantly in fluence the ways in which it is investigated and treated. This would not me an that the many other factors affecting bone mass and bone cell activity w ill be ignored, but rather these factors will be put in perspective. Resear ch to prevent or treat osteoporosis could be directed usefully to understan ding how osteoblasts, lining cells, and osteocytes respond to mechanically derived information and how these responses are converted into stimuli cont rolling structurally appropriate modeling and remodeling. Evidence suggesti ng that early strain-related responses of bone cells in males and females i nvolve the estrogen receptor (ER) could explain decreased effectiveness of this pathway when ER levels are low.