DROLOXIFENE INHIBITS CORTICAL BONE TURNOVER ASSOCIATED WITH ESTROGEN DEFICIENCY IN RATS

Droloxifene (DRO), an estrogen antagonist/agonist, has been shown to p ossess estrogen-like effects in inhibiting bone turnover leading to ca ncellous bone loss in ovariectomized (OVX) rats. The purpose of this s tudy was to determine the effects of DRO on cortical bone turnover in OVX rats. Sprague Dawley female rats at 5 months of age were sham-oper ated (sham, n=8) and orally treated with vehicle, or OVX (n=56) and or ally treated with either vehicle, DRO at 0.1, 1, 5, or 10 mg/kg/day, o r 17 alpha-ethynyl estradiol (EE) at 3 or 30 mu g/kg/day for 4 weeks. Static and dynamic cortical bone histomorphometry was performed on dou ble fluorescent labeled, undecalcified cross sections of tibial diaphy ses (proximal to the tibiofibular junction). There were no significant differences in tibial diaphyseal cross sectional area, marrow cavity area, and cortical bone area between groups after 4 weeks of administr ation. Periosteal mineralizing surface, mineral apposition rate, and b one formation rate-surface referent and endocortical eroded surface in creased significantly, while endocortical mineral apposition rate and bone formation rate-surface referent increased nonsignificantly in OVX controls compared to sham controls. Treatment with DRO at doses of 0. 1 to 10 mg/kg/day dose-dependently attenuated the OVX-induced higher b one formation indices in both the periosteal and endocortical surfaces and higher bone resorption index in the endocortical surface. At the highest dose (10 mg/kg/day), DRO completely inhibited the increases in bone formation and resorption indices in OVX rats. Similarly, EE at 3 0 mu g/kg/day inhibited the increase in periosteal and endocortical bo ne formation and endocortical bone resorption associated with estrogen deficiency in rats, while at 3 mu g/kg/day, EE decreased only periost eal mineral apposition rate in OVX rats. Our results indicated that DR O prevented OVX-induced higher bone turnover on endocortical surfaces and higher bone formation in periosteal surfaces of tibial diaphyses i n an identical manner to EE. Therefore, we concluded that DRO is an es trogen agonist on cortical bone in ovariectomized rats.