Parathyroid hormone is more effective than estrogen or bisphosphonates for restoration of lost bone mass in ovariectomized rats.
Parathyroid hormone is more effective than estrogen or bisphosphonates for restoration of lost bone mass in ovariectomized rats.
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DOI：
10.1210/endo.132.2.8425497
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发表时间：
1993-02
期刊：
影响因子：
4.8
通讯作者：
T. Wronski;C. Yen;H. Qi;L. Dann
中科院分区：
文献类型：
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作者：
T. Wronski;C. Yen;H. Qi;L. Dann
本研究旨在比较雌激素、双膦酸利塞膦酸酯(NE-58095)和甲状旁腺素(PTH)对去卵巢去骨量大鼠骨量恢复的疗效。此外，将这些单独治疗与甲状旁腺素+雌激素或甲状旁腺素+去甲肾上腺素-58095同时治疗的骨骼效应进行了比较。OVX大鼠在卵巢切除后的前4周不进行治疗，以允许出现中度的胫骨骨量减少。然后对这些动物进行为期5周、10周和15周的各种治疗。对其胫骨近端进行不脱钙处理，进行定量骨形态计量学研究。单独使用雌激素或NE-58095治疗骨质疏松的去势大鼠可降低骨转换，并防止在治疗期间发生额外的松质骨丢失。然而，这些治疗药物未能将去卵巢大鼠丢失的骨恢复到对照水平。相比之下，单独使用甲状旁腺素治疗的OVX大鼠表现出显著的骨形成刺激，导致松质骨量增加到比赋形剂治疗对照组大2倍的水平。同时应用甲状旁腺激素+雌激素和甲状旁腺素+去甲肾上腺素-58095的同时治疗也能有效地逆转去卵巢大鼠的松质骨量减少，但似乎并不比单独使用甲状旁腺素更有利于雌激素耗竭的骨骼。结果表明，甲状旁腺激素是一种强有力的骨形成刺激因子，能完全修复去骨性卵巢大鼠丢失的松质骨。此外，甲状旁腺激素的骨合成代谢作用比雌激素或双膦酸类要明显得多。这些在雌激素缺乏的动物模型中的发现支持PTH作为一种潜在的有效治疗卵巢切除和绝经后骨质疏松症的方法。
The study was designed to compare the therapeutic efficacy of estrogen, the bisphosphonate risedronate (NE-58095), and PTH for restoration of lost bone mass in osteopenic, ovariectomized (OVX) rats. In addition, the skeletal effects of these single treatments were compared to those of concurrent treatments with PTH + estrogen or PTH + NE-58095. OVX rats were untreated for the first 4 weeks postovariectomy to allow for the development of moderate tibial osteopenia. These animals were then subjected to the various treatments for periods of 5, 10, and 15 weeks. Their proximal tibiae were processed undecalcified for quantitative bone histomorphometry. Treatment of osteopenic OVX rats with estrogen or NE-58095 alone depressed bone turnover and prevented additional cancellous bone loss from occurring during the treatment period. However, these therapeutic agents failed to restore lost bone in OVX rats to control levels. In contrast, OVX rats treated with PTH alone exhibited a marked stimulation of bone formation which resulted in augmentation of cancellous bone mass to a level 2-fold greater than that of vehicle-treated control rats. Concurrent treatment of OVX rats with PTH + estrogen as well as PTH + NE-58095 also effectively reversed cancellous osteopenia in OVX rats, but did not appear to be more beneficial to the estrogen-deplete skeleton than treatment with PTH alone. The results indicate that PTH is a powerful stimulator of bone formation and completely restores lost cancellous bone in osteopenic OVX rats. Furthermore, the bone anabolic effects of PTH are much more pronounced than those of estrogen or bisphosphonates. These findings in an animal model of estrogen depletion provide support for PTH as a potentially effective treatment for oophorectomized and postmenopausal women with established osteoporosis.