Westerlind K C, Wronski T J, Ritman E L, Luo Z P, An K N, Bell N H, Turner R T
Department of Orthopedics, Mayo Foundation, Rochester, MN 55905, USA.
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4199-204. doi: 10.1073/pnas.94.8.4199.
Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced 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 strain.
雌激素缺乏所致的骨质流失与大鼠和人类骨转换增加有关。在去卵巢大鼠中研究了骨转换增加以及骨形成与骨吸收之间平衡改变在介导雌激素缺乏所致松质骨流失中的各自作用。去卵巢导致股骨远端骨转换增加。然而，松质骨优先在干骺端丢失，干骺端是一个正常情况下应变能较低的部位。在应变能较高的骨骺部位未观察到骨质流失。通过改变应变历程研究了机械应变在维持骨平衡中的作用。分别通过跑步机运动和功能失重在去卵巢大鼠的长骨中增加和降低机械应变。在轨道太空飞行期间和单侧坐骨神经切断术后实现功能失重。增加机械负荷可减少干骺端的骨质流失。相反，减少负荷会加剧干骺端的骨质流失，并导致骨骺部位骨质流失。最后，给去卵巢大鼠施用雌激素可减少失重肢体的骨质流失，并在单侧坐骨神经切断术后部分通过降低骨转换指标防止负重肢体骨质流失。这些结果表明，雌激素调节骨转换速率，但骨形成与骨吸收之间的总体平衡受主要机械应变水平的影响。
