ENDOCRINE AND PHARMACOLOGICAL SUPPRESSORS OF BONE TURNOVER PROTECT AGAINST OSTEOPENIA IN OVARIECTOMIZED RATS
ENDOCRINE AND PHARMACOLOGICAL SUPPRESSORS OF BONE TURNOVER PROTECT AGAINST OSTEOPENIA IN OVARIECTOMIZED RATS
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DOI：
10.1210/endo-125-2-810
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发表时间：
1989-08-01
期刊：
影响因子：
4.8
通讯作者：
CROOKE, LR
中科院分区：
文献类型：
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作者：
WRONSKI, TJ;DANN, LM;CROOKE, LR
本研究的目的是假设，内分泌和药理学抑制剂的骨转换防止骨质疏松症的发展，在雌激素缺乏。假手术对照组和卵巢切除（OVX）大鼠在手术后35或70天间歇性给予单独溶媒、雌激素或二膦酸盐化合物依替膦酸二钠（EHDP）和NE-58095 [2-（3-吡啶基）-2-羟基亚乙基-1，1-二膦酸二钠]。对它们的近端胫骨进行不脱钙处理，用于定量骨组织形态计量学。溶剂处理的OVX大鼠的特征为松质骨体积减少，成骨细胞表面、骨形成率和骨吸收率增加3- 4倍。用雌激素和NE-58095治疗OVX大鼠提供了对骨丢失的完全保护，并显著抑制了所有上述骨转换指数。用EHDP治疗的OVX大鼠表现出至少部分的骨丢失保护和骨转换降低。EHDP诱导轻度矿化缺陷，如胫骨皮质内表面矿化滞后时间延长所示。新的二膦酸盐化合物NE-58095不损害骨矿化。我们的研究结果表明，内分泌和药理学抑制剂的骨转换防止骨质减少的发展，在早期阶段的雌激素缺乏。如果在人类的临床试验证实，二膦酸盐化合物可能被证明是一种替代雌激素预防绝经后骨质流失。
This study was designed to the hypothesis that endocrine and pharmacological suppressors of bone turnover prevent the development of osteopenia during estrogen deficiency. Sham-operated control and ovariectomized (OVX) rats were treated intermittently with vehicle alone, estrogen, or the diphosphonate compounds etidronate disodium (EHDP) and NE-58095 [2-(3-pyridinyl)-2-hydroxyethylidene-1,1-bisphosphonate disodium] for 35 or 70 days after surgery. Their proximal tibiae were processed undecalcified for quantitative bone histomorphometry. Vehicle-treated OVX rats were characterized by decreased cancellous bone volume and 3- to 4-fold increases in osteoblast surface, bone formation rate, and bone resorption rate. Treatment of OVX rats with estrogen and NE-58095 provided complete protection against bone loss and signifcantly depressed all of the above indices of bone turnover. OVX rats treated with EHDP exhibited at least partial protection against bone loss and decreased bone turnover. EHDP induced a mild mineralization defect, as indicated by a prolonged mineralization lag time at the tibial endocortical surface. The new diphosphonate compound NE-58095 did not impair bone mineralization. Our results indicate that endocrine and pharmacological suppressors of bone turnover prevent the development of osteopenia during the early stages of estrogen deficiency. If confirmed by clinical trials in humans, diphosphonate compounds may prove to be an alternative to estrogen for the prevention of postmenopausal bone loss.