DROLOXIFENE, A NEW ESTROGEN ANTAGONIST AGONIST, PREVENTS BONE LOSS INOVARIECTOMIZED RATS

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 def icient by ovariectomy. Sprague-Dawley female rats were ovariectomized (OVX) or sham operated (sham) at 5 months of age and treated with 17 b eta-estradiol (E(2)) at 30 mu g/kg, sc, daily or with DRO at 5, 10, or 20 mg/kg . day, orally, for 4 weeks. At the time of death, body weigh t gain, uterine weight, and total serum cholesterol were measured. Bon e area, bone mineral content (BMC), and bone mineral density (BMD) of whole femora, distal femoral metaphyses, femoral shaft, and proximal f emora were determined ex vivo using dual energy x-ray absorptiometry. Static and dynamic cancellous bone histomorphometric analysis of proxi mal tibial metaphyses was performed in double fluorescent labeled, und ecalcified, 4- and 10-mu m longitudinal sections. Body weight gain in E(2)-treated OVX rats was significantly reduced compared to that in OV X controls, but was not different from that in sham controls. Body wei ght 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 E(2). Uterine weight in DRO-tr eated OVX rats was slightly, but significantly, increased from the veh icle-treated control value, and was significantly-lower than that ill sham controls and E(2)-treated