Skeletal effects of selective oestrogen receptor modulators (SERMs)

Women suffer a higher incidence of osteoporosis than men, in part due to oestrogen deficiency after menopause. In fact, the administration of oestrogen to post-menopausal women is associated with a decrease of bone resorption. Tamoxifen is a widely used selective oestrogen receptor modulator in women with breast cancer, which has been shown an agonistic profile in bone. However, tamoxifen seems less effective than oestradiol as an anti-resorptive agent and has no effect when the endogenous production of oestrogen is normal. Additionally, tamoxifen exhibits agonistic activity on the endometrium and has been suggested an oncogenic potential on that tissue. Raloxifene, a selective oestrogen receptor modulator from the benzothiophene family, behaves also as an agonist on the bone in both laboratory and clinical studies. Ongoing clinical trials confirm a protective effect of raloxifene similar to oestrogens. The Multiple Outcome of Raloxifene Evaluation (MORE) study is a prospective, randomized trial which, in a recent 2 year interim analysis, has shown that women suffering from osteoporosis receiving raloxifene had 42% fewer vertebral fractures than women receiving a placebo.