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Journal of Osteoporosis
Volume 2011, Article ID 240328, 7 pages
http://dx.doi.org/10.4061/2011/240328
Research Article

Testosterone and the Male Skeleton: A Dual Mode of Action

1Experimental Medicine and Endocrinology, Department of Experimental Medicine, K. U. Leuven, 300 Leuven, Belgium
2Division of Geriatric Medicine, Leuven University Hospital, Leuven, 300 Leuven, Belgium
3Gerontology and Geriatrics Section, Department of Experimental Medicine, K. U. Leuven, 300 Leuven, Belgium
4Leuven University Centre for Metabolic Bone Diseases, 300 Leuven, Belgium
5Molecular Endocrinology Laboratory, Department of Molecular Cell Biology, K. U. Leuven, 300 Leuven, Belgium
6Laboratory for Experimental Medicine and Endocrinology, Leuven University Hospital, Herestraat 49, 300 Leuven, Belgium

Received 13 April 2011; Accepted 4 July 2011

Academic Editor: Pawel Szulc

Copyright © 2011 Mieke Sinnesael et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Testosterone is an important hormone for both bone gain and maintenance in men. Hypogonadal men have accelerated bone turnover and increased fracture risk. In these men, administration of testosterone inhibits bone resorption and maintains bone mass. Testosterone, however, is converted into estradiol via aromatization in many tissues including male bone. The importance of estrogen receptor alpha activation as well of aromatization of androgens into estrogens was highlighted by a number of cases of men suffering from an inactivating mutation in the estrogen receptor alpha or in the aromatase enzyme. All these men typically had low bone mass, high bone turnover and open epiphyses. In line with these findings, cohort studies have confirmed that estradiol contributes to the maintenance of bone mass after reaching peak bone mass, with an association between estradiol and fractures in elderly men. Recent studies in knock-out mice have increased our understanding of the role of androgens and estrogens in different bone compartments. Estrogen receptor activation, but not androgen receptor activation, is involved in the regulation of male longitudinal appendicular skeletal growth in mice. Both the androgen and the estrogen receptor can independently mediate the cancellous bone-sparing effects of sex steroids in male mice. Selective KO studies of the androgen receptor in osteoblasts in male mice suggest that the osteoblast in the target cell for androgen receptor mediated maintenance of trabecular bone volume and coordination of bone matrix synthesis and mineralization. Taken together, both human and animal studies suggest that testosterone has a dual mode of action on different bone surfaces with involvement of both the androgen and estrogen receptor.