Physical activity in the androgen receptor knockout mouse: Evidence for reversal of androgen deficiency on cancellous bone

Disruption of the androgen receptor (AR) in male mice reduces cortical bone expansion and muscle mass during puberty and results in high bone turnover-related cancellous osteopenia. We hypothesized that voluntary wheel running during growth is able to rescue the effects of AR disruption on bone. To this end, 5-week-old AR knockout (ARKO) mice were randomized to a running group (cage with running wheel) and a sedentary group (cage without wheel) and followed-up until 16 weeks of age. Voluntary wheel running in ARKO mice did not influence body weight, muscle mass or periosteal bone expansion. Interestingly, voluntary running significantly reduced bone turnover in ARKO mice and prevented cancellous bone loss due to a preservation of trabecular number. Thus, voluntary running in ARKO mice was able to reduce cancellous bone resorption, suggesting that sustained exercise may potentially compensate the effects of androgen disruption on cancellous bone.