Droloxifene, a new estrogen antagonist/agonist, prevents bone loss in ovariectomized rats.
Droloxifene, a new estrogen antagonist/agonist, prevents bone loss in ovariectomized rats.
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屈洛昔芬是一种新型雌激素拮抗剂/激动剂，可预防卵巢切除大鼠的骨质流失。
作者：
H. Ke;H. Simmons;C. Pirie;D. Crawford;D. Thompson
研究新型雌激素拮抗剂/激动剂德洛昔芬（droloxifene， DRO）对卵巢切除后雌激素缺乏大鼠骨转换、骨量、血清总胆固醇和子宫重量的影响。Sprague-Dawley雌性大鼠在5月龄时切除卵巢（OVX）或假手术（sham），每天给予30微克/公斤的17 β -雌二醇（E2）或5、10或20毫克/公斤的DRO。每日口服，连用4周。在死亡时，测量体重增加、子宫重量和血清总胆固醇。采用双能x线骨密度仪测定全股骨、股骨远端、股骨干和股骨近端骨面积、骨矿物质含量（BMC）和骨矿物质密度（BMD）。在双荧光标记、未钙化、4微米和10微米纵剖面上对胫骨近端背骨进行静态和动态松质骨组织形态学分析。e2处理的OVX大鼠体重增加与OVX对照组相比显著降低，但与假对照组没有差异。与假药和OVX对照组相比，dro治疗的OVX大鼠体重增加明显减少。在OVX大鼠中，E2完全保留了子宫重量。dro处理的OVX大鼠的子宫重量较药液处理的对照组略有增加，但明显增加，明显低于假对照组和e2处理的OVX大鼠。sc注射E2对OVX大鼠血清总胆固醇无影响，而口服DRO 5 ~ 20mg /kg对OVX大鼠血清总胆固醇无影响。与假手术对照组和OVX对照组相比，每天降低了33-46%的血清总胆固醇。与假对照组相比，OVX降低了股骨远端外骺端BMC和骨密度，增加了股骨干的骨密度，对整个股骨和股骨近端BMC和骨密度无影响。E2或DRO均可阻止OVX引起的这些变化。5、10、20 mg/kg组胫骨近端干骺端骨小梁体积和骨小梁数量增加，骨小梁分离率、破骨细胞周长百分比、破骨细胞周长百分比、矿化周长百分比、矿物附着率、骨形成率和骨周转率降低。与OVX对照组相比。DRO处理的OVX大鼠的这些松质骨组织形态学指标与e2处理的OVX大鼠或假对照组没有差异，表明DRO完全阻止了OVX引起的大鼠骨转换的增加和骨量的减少。（摘要删节为400字）
The purpose of this study was to determine the effects of droloxifene (DRO), a new estrogen antagonist/agonist, on bone turnover, bone mass, total serum cholesterol, and uterine weight in rats made estrogen deficient by ovariectomy. Sprague-Dawley female rats were ovariectomized (OVX) or sham operated (sham) at 5 months of age and treated with 17 beta-estradiol (E2) at 30 micrograms/kg, sc, daily or with DRO at 5, 10, or 20 mg/kg.day, orally, for 4 weeks. At the time of death, body weight gain, uterine weight, and total serum cholesterol were measured. Bone area, bone mineral content (BMC), and bone mineral density (BMD) of whole femora, distal femoral metaphyses, femoral shaft, and proximal femora were determined ex vivo using dual energy x-ray absorptiometry. Static and dynamic cancellous bone histomorphometric analysis of proximal tibial metaphyses was performed in double fluorescent labeled, undecalcified, 4- and 10-microns longitudinal sections. Body weight gain in E2-treated OVX rats was significantly reduced compared to that in OVX controls, but was not different from that in sham controls. Body weight gain in DRO-treated OVX rats was decreased significantly compared to that in both sham and OVX controls. In OVX rats, uterine weight was completely preserved by treatment with E2. Uterine weight in DRO-treated OVX rats was slightly, but significantly, increased from the vehicle-treated control value, and was significantly lower than that in sham controls and E2-treated OVX rats. Treatment with sc injection of E2 in OVX rats had no effect on total serum cholesterol, whereas OVX rats orally treated with DRO at 5-20 mg/kg.day decreased total serum cholesterol by 33-46% compared to levels in sham and OVX controls. Compared to sham controls, OVX decreased BMC and BMD of distal femoral metaphyses, increased BMD of the femoral shaft, and had no effect on BMC and BMD of whole femora and proximal femora. Treatment with either E2 or DRO prevented these changes induced by OVX. Proximal tibial metaphyseal trabecular bone volume and trabecular number were increased, and trabecular separation, percent osteoclast perimeter, osteoclast number, percent mineralizing perimeter, mineral apposition rate, bone formation rate, and bone turnover rate were decreased in 5, 10, or 20 mg/kg.day DRO-treated OVX rats compared to OVX controls. These cancellous bone histomorphometric indexes in DRO treated OVX rats did not differ from those in E2-treated OVX rats or sham controls, suggesting that DRO completely prevented the increases in bone turnover and the decrease in bone mass induced by OVX in rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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