DROLOXIFENE, A NEW ESTROGEN ANTAGONIST AGONIST, PREVENTS BONE LOSS IN OVARIECTOMIZED 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 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 (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 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-mu m longitudinal sections. Body weight gain in E(2)-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 E(2). Uterine weight in DRO-treated OVX rats was slightly, but significantly, increased from the vehicle-treated control value, and was significantly-lower than that ill sham controls and E(2)-treated