Adrenal androgen mediates the association between obesity and accelerated skeletal maturation in children and adolescents

Abstract

Childhood obesity is associated with advanced bone age (BA), but the underlying endocrine mechanisms remain unclear. We investigated the mediating role of dehydroepiandrosterone sulfate (DHEA-S) in the relationship between adiposity and skeletal maturation. This retrospective study included 1,252 children aged 4–12 years from a single center. Skeletal maturation was assessed using the BA-to-chronological age (CA) ratio. Advanced maturation was defined as BA/CA > 1.1. Mediation analysis was performed to evaluate whether DHEA-S explains the association between BMI SDS and skeletal maturation. Body mass index standard deviation score (BMI SDS) and DHEA-S were independently associated with the BA/CA ratio (p < 0.05). In boys younger than 9 years, DHEA-S demonstrated good discriminative performance for advanced maturation (Area under the curve = 0.817). Mediation analysis showed that DHEA-S significantly mediated the association between BMI and BA/CA in boys < 9 years (β = 0.512, p = 0.024) and in girls ≥ 8 years (β = 0.377, p = 0.003). In young boys, the direct effect of BMI became non-significant after inclusion of DHEA-S, consistent with substantial mediation by adrenal androgens. Adrenal androgen activity, reflected by DHEA-S, represents a significant endocrine pathway linking obesity to accelerated skeletal maturation. The magnitude of this mediation varies by age and sex, highlighting developmentally specific windows of endocrine-metabolic interaction in growing children.