Divergent effects of EDCs on bone maturation: Role of body mass index and puberty

Exposure to endocrine-disrupting chemical (EDC) mixture and its association with bone maturation in children remain unclear. In this case-control study, the relationship between EDC exposure and accelerated bone maturation in girls aged 6-13 years (n = 501) was investigated using data from the Evaluation and Monitoring on School-based Nutrition and Growth in Shenzhen study. Urinary concentrations of 11 phthalate metabolites, as well as seven bisphenols, nonylphenol (NP), and triclosan, were measured. Bone age (BA) was assessed using a mobile X-ray bone rheometer via the TW3-RUS method. Statistical analyses included binary logistic regression, weighted quantile sum, Bayesian Kernel Machine Regression, mediation effect analysis, and quantile regression. Girls with advanced BA had significantly lower median concentrations of mono-isobutyl phthalate (MiBP), mono(2-ethylc5-hydroxyhexyl) phthalate, and NP. Only total monoethyl phthalate (MEP) was positively associated with advanced BA in prepubertal girls, whereas mono-methyl phthalate (MMP), MiBP, bisphenol A (BPA), NP, and total EDCs were negatively associated. Negative correlations were observed between several phthalate metabolite concentrations and height for the BA standard deviation score. Body mass index (BMI) and puberty mediated the associations between mono-methyl phthalate concentration and NP with advanced BA. The findings reveal that MMP, MEP, BPA, MiBP, and NP exposure exert divergent effects and pubertal sensitivity differences on accelerated bone maturation, with BMI and pubertal stage playing mediating roles. These findings have significant public health implications, given the pervasiveness of EDCs and the increasing trends in overweight/obesity, earlier puberty initiation, and accelerated bone maturation.