Antiestrogens bone loss prevention

While tamoxifen was being used for the treatment or prevention of breast cancer, it was discovered by chance that this compound had positive effects on bone, although its antiestrogenic activity was originally expected to accelerate and not to reduce bone loss (Evans and Turner, 1995 Jordan, 1993). 

Menopause is thus the condition in most urgent need of tissue- or cell-targeted endocrine therapy. In fact, estrogen-like compounds are required for prevention of bone loss and cardiovascular disease. On the other hand, for the breast and endometrium, the ideal approach is a pure antiestrogen that would inhibit the development and growth of breast and endometrial carcinoma. The effects required in the skeletal and cardiovascular systems (estrogenic) are thus the opposite of those required in the breast and endometrium, for which antiestrogenic activity is recommended. 

These compounds, however, do not possess cell or tissue specificity and show antiestrogenic activity in all the tissues tested. For example, ICI 164,384 and ICI 182,780 do not lower serum cholesterol levels and do not prevent ovariectomy-induced bone loss (Dodds et al., 1993 Jordan, 1992 Wakeling, 1993), thus limiting our interest in them when there are other compounds that also exert pure antiestrogenic activity in the breast and uterus, while at the same time preventing bone loss and decreasing serum cholesterol (Labrie et al., 1999). 

The present data clearly demonstrate that in the rat, low doses of EM-800 prevent bone loss and lower serum cholesterol levels without stimulatory effect on the endometrium, and previous studies have described the pure antiestrogenic activity of this compound in the mammary gland. Such data are encouraging and suggest that the antiestrogen EM-652 and its precursor EM-800 have the potential for exerting simultaneous beneficial effects on four important aspects of women s health, namely, prevention and/or treatment of breast and uterine cancer, osteoporosis, and coronary heart disease. 

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