Kalu D N, Salerno E, Liu C C, Echon R, Ray M, Garza-Zapata M, Hollis B W
Department of Physiology, University of Texas Health Science Center, San Antonio 78284-7756.
Bone Miner. 1991 Nov;15(2):109-23. doi: 10.1016/0169-6009(91)90002-h.
This study was undertaken to examine the separate and combined effects of tamoxifen (T), estrogen (E2) and progesterone (P) treatment on ovariectomized (Ooph) rats. The animals were treated for 40 days. Ovariectomy reduced cancellous bone volume at the proximal tibia by 50%. Estradiol treatment completely prevented the bone loss and further increased bone volume 77% over the level for the control group. Tamoxifen also prevented the ovariectomy induced bone loss, but significantly reduced the increase in cancellous bone induced by estradiol. In the ovariectomized rats, cancellous bone apposition rate increased 23%. This increase was suppressed 63% by estradiol, and only 18% by tamoxifen. Tamoxifen significantly suppressed the inhibitory effect of estradiol on cancellous bone apposition rate. In contrast, the effect of progesterone treatment was only marginal. Our findings indicate that the action of tamoxifen on bone is influenced by the ambient level of circulating estradiol, such that in estrogen deficiency, tamoxifen has a weak estrogen agonist action on bone, and in the presence of estrogen it has anti-estrogen actions, with the dose level and mode of administration employed. These conclusions have implications for the use of tamoxifen in the treatment of pre- and postmenopausal women.
本研究旨在探讨他莫昔芬（T）、雌激素（E2）和孕激素（P）单独及联合治疗对去卵巢（Ooph）大鼠的影响。动物接受治疗40天。去卵巢使胫骨近端的松质骨体积减少50%。雌二醇治疗完全阻止了骨量丢失，并使骨体积比对照组水平进一步增加77%。他莫昔芬也阻止了去卵巢诱导的骨量丢失，但显著降低了雌二醇诱导的松质骨增加。在去卵巢大鼠中，松质骨沉积率增加了23%。这种增加被雌二醇抑制了63%，而被他莫昔芬仅抑制了18%。他莫昔芬显著抑制了雌二醇对松质骨沉积率的抑制作用。相比之下，孕激素治疗的效果仅为边缘性。我们的研究结果表明，他莫昔芬对骨骼的作用受循环雌二醇环境水平的影响，即在雌激素缺乏时，他莫昔芬对骨骼具有弱雌激素激动剂作用，而在有雌激素存在时，根据所用剂量水平和给药方式，它具有抗雌激素作用。这些结论对他莫昔芬在绝经前和绝经后妇女治疗中的应用具有启示意义。
