Oestrogen and the skeleton
Oestrogen plays a major role in the regulation of bone turnover during the different phases of life. During puberty, the increase in oestrogen has a bisphasic effect on growth, stimulating the secretion of growth hormone and promoting the closure of the growth plate. It has an effect on modelling to stimulate endosteal apposition and inhibit periosteal apposition. It has an effect on bone remodelling, to decrease the rate of bone remodelling, and possibly to have an anabolic effect on osteoblasts. The effects of oestrogen on modelling and remodelling persist until the menopause. After the menopause, the residual oestrogen is still an important regulator of bone turnover. The mechanisms by which oestrogen regulates bone turnover are now better understood, particularly its effects on the local production of cytokines and its action by modulating the production of osteoprotegerin and RANK-ligand. The importance of residual oestrogen is best shown with the use of aromatase inhibitors. These decrease the level of oestrogen to very low levels in all women and as a result there is a further increase in bone turnover and a further acceleration in the rate of bone loss. The standard approach to the prevention of postmenopausal bone loss has been the use of oestrogen replacement therapy; however, with the concerns over the increased risk of stroke, cardiovascular disease and breast cancer, there is great interest in developing oestrogens that are agonists on bone but antagonists in other tissues, the so-called 'selective oestrogen receptor modulators' or SERMs.