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  • Title: Droloxifene, a new estrogen antagonist/agonist, prevents bone loss in ovariectomized rats.
    Author: Ke HZ, Simmons HA, Pirie CM, Crawford DT, Thompson DD.
    Journal: Endocrinology; 1995 Jun; 136(6):2435-41. PubMed ID: 7750465.
    Abstract:
    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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