Androgen exposure and the maintenance of skeletal integrity in aging men

Abstract

Androgen receptors that are of similar character to those in classical androgen target tissues have been reported in primary cultures of human osteoblasts, and a stimulatory effect of androgens on osteoblastic cell proliferation and differentiation has been demonstrated. In addition, recent evidence suggests that androgens may also affect bone resorption by inhibition of osteoclastic differentiation. In line with these anabolic androgen effects noted in vitro, animal studies in different orchidectomized rat models have provided evidence that androgen secretions are needed for normal skeletal growth and maintenance in vivo. The increasing evidence for the involvement of androgens in bone remodeling has given rise to considerable speculation as to whether bone loss and fracture occurrence in aging men might, at least partially, result from androgen deficiency. Numerous studies have provided evidence that the aging process in men is accompanied by changes in the hypothalamic-pituitary-gonadal axis that result in notable declines in serum levels of testosterone and, to a lesser degree, dihydrotestosterone. However, the skeletal impact of these deficiencies remains to be clarified. The extent to which bone loss in older men is accounted for by androgen status has only been studied cross-sectionally and no attempts have been made as yet to examine the antifracture efficacy of androgen substitution. Future studies are needed to assess the impact of different degrees of androgen deficiency on skeletal maintenance in aging men and to define the clinical potential of testosterone substitution in attenuating bone loss and reducingfracture risk.