Impact of Aromatase Inhibitor Therapy on Bone Turnover, Cortical Bone Growth and Vertebral Morphology in Pre- and Peripubertal Boys with Idiopathic Short Stature

Abstract

In this randomized placebo-controlled study we examined the influence of aromatase inhibition on bone turnover, cortical bone growth, and vertebral body morphology in peripubertal boys. Thirty peripubertal boys with idiopathic short stature were treated with the aromatase inhibitor letrozole or placebo for 2 years. During treatment and posttreatment follow-up, dual-energy X-ray absorptiometry (DXA)-assessed bone mineral density, metacarpal index (MCI), and markers of bone turnover were examined. Vertebral morphology was examined by DXA after cessation of treatment. In letrozole-treated boys, the concentrations of the bone resorption marker urine aminoterminal telopeptide of type I collagen initially increased and thereafter slowly declined while the concentrations of the bone formation markers serum aminoterminal propeptide of type I collagen and serum alkaline phosphatase remained unchanged or slightly increased, respectively. In placebo-treated boys, all markers of bone turnover increased significantly during treatment. Among those who progressed into puberty, metacarpal index (MCI) increased more in the letrozole-treated than in the placebo-treated boys during treatment (25 vs. 9%, p = 0.007). The change in MCI correlated with the testosterone-to-estradiol ratio (r = 0.59, p = 0.02). Vertebral deformities were detected in 6 out of 13 boys receiving letrozole and in 4 out of 11 receiving placebo (p = 0.70). Aromatase inhibition suppresses bone turnover, possibly through an androgen-mediated effect. In pubertal boys, treatment stimulates cortical bone growth by increasing the testosterone-to-estradiol ratio.