ABSTRACT
INTRODUCTION Estrogen deficiency arising after the menopause or upon surgical removal of the ovaries leads to accelerated bone loss and promotes the development of postmenopausal osteoporosis in approximately one-third of the female population1. The primary consequence of the relative lack of estrogen is an increase in bone resorption, which can be attributed to marked increases in both the number and resorptive activity of osteoclasts2. Although bone formation also shows a notable increase upon the propagation of estrogen deficiency, the rise in resorption exceeds the increase in formation, the net changes leading to loss of bone mass. While bone resorption is carried out by osteoclasts, the paths by which estrogen exerts its inhibitory effects on these cells are still under debate. Although osteoclasts possess estrogen receptors and thus can be direct targets of estrogen action, a considerable part of the effect is believed to be indirect and mediated by osteoblasts and various cells of the immune system3. Research attempting the clarification of how estrogen acts on bone metabolism includes: the direct effects of sex steroids on osteoclasts investigated in simple in vitro systems; the impact of sex steroid receptor deficiency on osteoclastic function and skeletal homeostasis using data from estrogen and androgen receptor knock-out mice; and finally the in vivo effects of sex steroids on bone turnover assessed in various clinical settings. The current review combines these three major approaches to bring forward the present understanding of the action of sex steroids on osteoclast function and overall bone turnover.
