[Anti-estrogens and bone tissue]

Anti-oestrogens are a class of non-steroid compounds with, depending on the tissue, oestrogen-antagonist or oestrogen-agonist actions resulting from different mechanisms, especially by binding to oestrogen receptors. These compounds are commonly called anti-oestrogens because of their extensive use in treating breast cancer. Tamoxifen, the first of these complex compounds, has a partial agonist effect on the endometrium and also affects bone and lipid metabolism. Currently, our knowledge of anti-oestrogen action on bone is based on experimental work and a few clinical trials with tamoxifen. The animal studies show that tamoxifen has a preventive effect against bone hyper-remodelling resulting form ovariectomy in the rat. Most of the clinical studies, including the most recent, show that tamoxifen has no deleterious effect, and possibly even a moderate protective effect against bone loss, in menopaused women. This effect on bone tissue, together with lowered plasma cholesterol levels, has led to the development of other compounds with a bone and lipid agonist effect and secondary effects limited to endometrial hyperplasia. Third generation compounds include droloxifen keoxifen (or raloxifen) currently under investigation. This research should lead to wider indications for anti-oestrogens in the prevention of the effects of post-menopause oestrogen deficiency, particularly in patients with contraindications for oestrogen therapy.