Mechanical strain and bone cell function: A review

1. The fracture resistance of bones is established and maintained as the result of an adaptive mechanism in which bone cells' modeling and remodeling activity is directly or indirectly influenced by their strain environment. 2. The mechano-responsive cells are most likely osteocytes and osteoblasts. Many studies show acute mechanically related changes in behavior of these cells in culture but many of these have not been related to the long term control of remodeling on which adaptive control of bone architecture depends. Not all bone cells' responses to mechanical stimuli are part of the cascade of responses involved in adaptive (re)modeling. The specific mechanical stimuli to which osteocytes and osteoblasts respond in vivo probably include changes in strain itself and strain generated changes in their fluid environment. Physiologic levels of bone strain have been demonstrated to be directly and indirectly involved in increasing the release of signaling molecules and anabolic growth factors, such as PGE2, PGI2, NO, and IGF-I and IGF-II, that stimulate bone cell proliferation and matrix formation. 3. The osteoregulatory nature of a natural strain regimen appears to be determined primarily by the peak strains achieved, the rate of strain change, and the extent to which the strain distribution is different from the normal strains to which the bone has adapted. Loading regimens producing high strains, high strain rates and unusual strain distributions appear to have a high osteoregulatory potential stimulating osteogenic responses and maintaining high bone mass. Static strains, strains which change slowly, and 'error-free' strains may have little or no osteoregulatory potential and may thus permit (if not engender) bone loss and low bone mass. 4. The positive osteoregulatory influence of a strain regimen is most effective during growth. Appropriate activity at this time can lead to a larger and more robust skeleton that can maintain its strength despite loss of bone tissue later in life. 5. The reduced ability to maintain bone strength in postmenopausal women is a failure of the normally adaptive response to mechanical strain under the conditions of the postmenopausal state. Evidence that early strain-related responses of bone cells involve the estrogen receptor could explain the decreased effectiveness of this pathway when estrogen receptor levels are low postmenopausally. The high strains assumed to be associated with low bone mass may downregulate ERα expression thus further diminishing the responsiveness of bones to loading.