Purpose of review
The review is timely given recent advances regarding mechanisms of androgen action on bone cells and in humans. Osteoporosis in men is an important public health problem. An improved understanding of the role of androgens in the pathophysiology of bone loss will lead to new treatments.
Androgen receptors are present in most bone cells. Testosterone acts on bone both directly via the androgen receptor and indirectly, following aromatization, via the oestrogen receptor. During skeletal modelling, ERα is critical for longitudinal bone growth. For periosteal growth and bone expansion, androgen receptor activation has a positive effect, whereas ERα activation is inhibitory. During skeletal remodelling, both receptor pathways generate similar and additive effects on bone.
Androgen deficiency is a common secondary cause of osteoporosis in men and should be treated with testosterone, particularly in symptomatic men. However, lack of efficacy data for testosterone in osteoporosis means it is less useful as a first-line treatment in men with age-related declines in testosterone and osteoporosis, when other agents such as bisphosphonates and parathyroid hormone are effective.
Randomized, placebo-controlled trials of testosterone therapy in men with age-related declines in testosterone and osteoporosis are needed, and should carefully evaluate potential risks, as well as its efficacy in reducing fractures and other health benefits.