Association of obesity and adrenal androgen levels with bone age progression in boys with premature adrenarche

Abstract

Purpose: Both premature adrenarche (PA) and obesity are closely linked to increases in bone age (BA). However, the mechanisms underlying these associations are unclear as research data, particularly in boys, are lacking. Therefore, our aim in this study was to test for an association between obesity and BA progression in boys with PA and to assess the role of adrenal androgen in the mediation of any identified association. Methods: We retrospectively analyzed data from medical records of prepubertal boys with PA. Participants were categorized into 2 groups based on the difference between their BA and chronological age (CA), BA–CA≥1 and BA–CA<1. Results: Among 67 boys having a mean age of 8.3±0.7 years, the 27 boys in the BA–CA≥1 group had significantly higher body mass index (BMI) z-scores (1.7±0.9 vs. 1.0±1.3, P=0.022) and dehydroepiandrosterone sulfate (DHEA-S) z-scores (1.7±1.3 μg/dL vs. 1.1±0.7 μg/dL, P=0.020), than the 40 boys in the BA–CA<1 group. Multivariate regression analyses revealed a significant association between BMI z-score and BA progression for the BA–CA≥1 group, even after adjusting for DHEA-S z-score, odds ratio=1.605 with P=0.048. Mediation analyses indicated that the direct effect of BMI z-score on BA–CA was statistically significant, β=0.2190 with P=0.039; however, the indirect effect of BMI z-score on BA–CA through DHEA-S z-score was not significant. Conclusion: In boys with PA, higher DHEA-S z-scores and BMI z-scores were associated with BA–CA. However, DHEA-S did not mediate the relationship between obesity and BA progression. Our data suggested that in boys with obesity and PA, the rapid progression of skeletal maturation is primarily the result of a direct impact of obesity on BA and not due to an increase in adrenal androgen levels.