ESTROGEN INHIBITS BONE-RESORPTION BY DIRECTLY INDUCING APOPTOSIS OF THE BONE-RESORBING OSTEOCLASTS

Estrogen deficiency causes bone loss, which can be prevented by estrog en replacement therapy. Using a recently developed technique for isola tion of highly purified mammalian osteoclasts, we showed that 17 beta- estradiol (E-2) was able to directly inhibit osteoclastic bone resorpt ion. At concentrations effective for inhibiting bone resorption, E-2 a lso directly induced osteoclast apoptosis in a dose-and time-dependent manner. ICI164,384 and tamoxifen, as pure and partial antagonists, re spectively, completely or partially blocked the effect of E-2 on both inhibition of osteoclastic bone resorption and induction of osteoclast apoptosis. These data suggest that the protective effects of estrogen against postmenopausal osteoporosis are mediated in part by the direc t induction of apoptosis of the bone-resorbing osteoclasts by an estro gen receptor-mediated mechanism.