The Effects of Selective Estrogen Receptor Modulators in Bone





Thomas A. Brown

Pfizer Inc




Estrogen is the gold standard for the prevention of bone loss in postmenopausal women. However, objectionable side effects with estrogen and concerns about breast cancer have limited compliance among women. Selective estrogen receptor modulators (SERMS), a new class of agents including raloxifene, work through the estrogen receptor (ER), retain many of the positive effects of estrogen, yet minimize some of the unwanted side effects of estrogen. In postmenopausal women, SERMs have demonstrated the ability to prevent bone loss and skeletal fractures. Further, the positive effects on bone are accompanied by significant reductions in breast cancer in women treated with raloxifene.

The ability of SERMs to inhibit bone loss has been well characterized in preclinical models of osteoporosis. Utilizing the ovariectomized (OVX) rat as a model for postmenopausal bone loss, numerous SERMs have been identified to have potential in the prevention of bone loss. SERMs that have shown the ability to prevent bone loss in animal models include: raloxifene, droloxifene, tamoxifen, lasofoxifene, idoxifene, and levomeloxifene. Each of these SERMs bind with high affinity to the estrogen receptor and appear to act in bone in a similar manner to estrogen. Data suggest that both SERMS and estrogen inhibit bone turnover via their ER-mediated effects on osteoclastogenesis. Emerging evidence points to the SERM-mediated induction of apoptosis as a mechanism for the inhibition of osteoclast formation. More recent data from preclinical models suggest that SERMs also inhibit bone loss in orchidectomized male rats, further suggesting that SERMs may also have utility in the prevention of bone loss in males. Taken together, these data suggest that SERMS offer a significant advance in prevention and treatment of osteoporosis.







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