ESTROGEN REGULATES THE RATE OF BONE TURNOVER BUT BONE BALANCE IN OVARIECTOMIZED RATS IS MODULATED BY PREVAILING MECHANICAL STRAIN

Estrogen deficiency induced bone loss is associated with increased bon e turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorptio n in mediating estrogen deficiency-induced cancellous bone loss was in vestigated in ovariectomized rats. Ovariectomy resulted in increased b one turnover in the distal femur. However, cancellous bone was prefere ntially lost in the metaphysis, a site that normally experiences low s train energy. No bone loss was observed in the epiphysis, a site exper iencing higher strain energy. The role of mechanical strain in maintai ning bone balance was investigated by altering the strain history. Mec hanical strain was increased and decreased in long bones of ovariectom ized rats by treadmill exercise and functional unloading, respectively . Functional unloading was achieved during orbital spaceflight and fol lowing unilateral sciatic neurotomy. Increasing mechanical loading red uced bone loss in the metaphysis. In contrast, decreasing loading acce ntuated bone loss in the metaphysis and resulted in bone loss in the e piphysis. Finally, administration of estrogen to ovariectomized rats r educed bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strai n.