Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain
Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain
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DOI：
10.1073/pnas.94.8.4199
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Turner, RT
中科院分区：
文献类型：
--
作者：
Westerlind, KC;Wronski, TJ;Turner, RT
雌激素缺乏引起的骨丢失与大鼠和人类骨转换增加有关。在卵巢切除大鼠中，研究了骨转换增加和骨形成与骨吸收之间平衡改变在介导雌激素缺乏诱导的松质骨丢失中的各自作用。卵巢切除术导致股骨远端骨转换增加。然而，松质骨优先在干骺端丢失，这是一个通常经历低应变能的部位。在骨骺中没有观察到骨丢失，该部位经历更高的应变能。通过改变应变历史研究了机械应变在维持骨平衡中的作用。跑台运动和功能性去负荷分别增加和减少了去卵巢大鼠长骨的机械应变。在轨道航天飞行和单侧坐骨神经切断术后实现了功能卸载。增加机械负荷可减少干骺端的骨丢失。相反，降低负荷加重了干骺端的骨丢失，并导致骨骺的骨丢失。最后，给予雌激素卵巢切除大鼠减少骨丢失的卸载和防止损失的负载肢体后，单侧坐骨神经切断术的一部分，通过降低骨转换指数。这些结果表明，雌激素调节骨转换率，但骨形成和骨吸收之间的总体平衡受到机械应变水平的影响。
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.