Androgens and the skeleton.
Loss of estrogens or androgens causes bone loss by increasing the rate of bone remodeling, and also causes an imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, treatment with androgens, as well as estrogens, maintains cancellous bone mass and integrity, regardless of age or sex. Both androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs) can exert these effects, but the relative contribution of these 2 pathways remains uncertain. Androgens, like estrogens, stimulate endochondral bone formation at the start of puberty, whereas they induce epiphyseal closure at the end of puberty, thus, they have a biphasic effect. Androgen action on the growth plate is, however, clearly mediated via aromatization into estrogens and interaction with ER alpha. Androgens increase, while estrogens decrease radial growth. This differential effect of the sex steroids may be important because bone strength in males seems to be determined by higher periosteal bone formation and, therefore, greater bone dimensions. Experiments in mice suggest that both the AR and ER alpha pathways are involved in androgen action on radial bone growth. ER beta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. This androgen action on bone is mediated by the AR and ER alpha.
Lindberg
M K
MK
Division of Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. Marie.Lindberg@medic.gu.se
Vandenput
L
L
Movèrare Skrtic
S
S
Vanderschueren
D
D
Boonen
S
S
Bouillon
R
R
Ohlsson
C
C
D000728:Androgens / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism / Q000517:prevention & control; D010521:Periosteum / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism
D000728:Androgens; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen