Relationship of testosterone and osteocalcin levels during growth

Recent studies in mice have demonstrated that osteocalcin (OCN) regulates testosterone (T) production in males but not in females. We hypothesized that this novel bone-testis axis may be most relevant during rapid skeletal growth to help maximize bone size. Thus we measured serum T, total and undercarboxylated (UC) OCN, and periosteal circumference at the radius in 56 boys (bone age 4 to 20 years). T was correlated with OCN (bone-age-adjusted r=0.30, p=.024), with a similar trend for UC OCN. T began to increase in the boys at bone age 11 years, and OCN peaked at bone age 14 years. Thus we divided the boys into three groups: 4 to 10 years (n=16), 11 to 14 years (n=18), and 15 to 20 years (n=22). In boys of bone age 11 to 14 years (but not the other two groups), OCN was correlated with T (r=0.57, p=.013), with a similar trend for UC OCN; T, in turn, was correlated with periosteal circumference (r=0.75, p<.001). Collectively, these findings support the recent observations in mice of a novel bone-testis axis. Moreover, our data suggest that in human males, this axis may be most relevant during rapid skeletal growth, when T levels are rising under the influence of the hypothalamic-pituitary axis and OCN is increasing due to skeletal growth. During this phase, OCN may further stimulate testicular T production, which, in turn, contributes to an increase in bone size.