Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol.
Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol.
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DOI：
10.1172/jci116483
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发表时间：
1993-06
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影响因子：
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通讯作者：
V. Shen;D. Dempster;R. Birchman;R. Xu;R. Lindsay
中科院分区：
文献类型：
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作者：
V. Shen;D. Dempster;R. Birchman;R. Xu;R. Lindsay
为了评估联合使用抗吸收和骨形成促进剂治疗绝经后骨质疏松症的可能性，我们研究了联合和单独给药雌激素（17 β -雌二醇，30微克/公斤/天，s.c）和甲状旁腺激素（rPTH[1-34]， 40微克/公斤/天，s.c）对去卵巢（Ovx）大鼠胫骨近端的影响。治疗持续4周，分别于术后1、3、5周开始。Ovx导致松质骨体积（Cn-BV/TV）和小梁连通性的快速损失，这是由二维支撑分析确定的。当以预防模式给药时，ovx后1周开始治疗，雌激素或PTH单独治疗可保持Cn-BV/TV和小梁连通性，雌激素和PTH联合治疗可使Cn-BV/TV增加40%，同时保持与假手术动物相当的小梁连通性。当以治疗模式给骨质疏松症的大鼠进行治疗时，在ovx后3或5周开始治疗，雌激素或PTH单独治疗可防止连接性和Cn-BV/TV的进一步丧失，而联合治疗可使小梁连接性参数之一（节点到节点支撑长度）改善300%，Cn-BV/TV增加106%，这与治疗开始时的骨骼状态有关。这种联合治疗的有益效果来自于雌激素防止骨吸收加速的能力，同时，甲状旁腺激素促进骨形成。这些数据表明，在动物模型中，可以设计治疗方法来治愈与骨质疏松症相关的骨骼缺陷。
To evaluate the potential use of a combination of antiresorption and bone formation-promoting agents as a treatment for postmenopausal osteoporosis, we examined the effects of combined and separate administration of estrogen (17 beta-estradiol, 30 micrograms/kg per d, s.c.) and parathyroid hormone (rPTH [1-34], 40 micrograms/kg per d, s.c.) on the proximal tibia of ovariectomized (Ovx) rats. The treatments lasted for 4 wk and were initiated 1, 3, and 5 wk after surgery. Ovx resulted in rapid loss of cancellous bone volume (Cn-BV/TV) as well as trabecular connectivity, as determined by two dimensional strut analysis. When administered in a preventive mode, treatment beginning 1 wk post-Ovx, estrogen or PTH treatment alone preserved Cn-BV/TV and trabecular connectivity, and combined estrogen and PTH treatment caused a 40% increment in Cn-BV/TV while maintaining comparable trabecular connectivity with that seen in the Sham-operated animals. When administered in a curative mode to rats with established osteoporosis, treatments beginning 3 or 5 wk post-Ovx, estrogen or PTH treatment alone prevented further loss of connectivity and Cn-BV/TV, whereas the combined treatment resulted in as much as a 300% improvement in one of the parameters of trabecular connectivity, node to node strut length, and a 106% increase in Cn-BV/TV, with respect to the bone status at the initiation of treatment. The beneficial effects of this combined treatment derive from estrogen's ability to prevent accelerated bone resorption and, simultaneously, PTH's promotion of bone formation. These data demonstrate, in an animal model, that therapies can be devised to cure the skeletal defects associated with established osteoporosis.