Sex Steroid Effects on Bone Metabolism

This chapter reviews the molecular structures, biosynthesis, and mechanism of action of the major clinically relevant sex steroids. The identification of estrogen and androgen receptors in bone cells was followed by a host of studies on the effects of sex steroids, in particular, estrogen, on ostoblasts and ostoclasts. This has led to the identification of candidate autocrine and paracrine mediators of estrogen and androgen action in bone. Although, important gaps remain in the understanding of the direct effects of sex steroids on bone cell functioning. Recent genetic, epidemiologic, and direct interventional evidence has also challenged traditional notions of the relative importance of estrogen on bone metabolism in men. While androgens clearly have significant effects on male skeleton, estrogen may also play a key role in males; conversely, androgens have important skeletal effects in women. These dual roles for estrogen and androgens have long been known in reproductive tissues, and now also appear to be true for the skeleton. Sex steroids also have important, indirect effects on bone metabolism via their effects on intestinal calcium absorption and renal calcium handling. While much has been learned in recent years on sex steroid effects on bone, this is a rapidly evolving area. Future studies are likely to reveal new insights, both into the mechanisms of sex steroid action on bone, as well as the relative contributions of estrogens versus androgens towards bone metabolism in both sexes.