Factors affecting bone maturation in 423 Chinese girls aged 4-8 years with isolated premature thelarche

Abstract Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age, but IPT girls requiring further investigations show another trend. We analysed BA and possible potentiating factors in girls aged 4-8 years with IPT. Methods: IPT girls aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were divided into two groups with advanced BA of 2 years as the cutoff. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups seperately according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS to compare BA. Results: Overall, 423 subjects were classified into the advanced BA (48.7%, n=206) and control groups (51.3%, n=217). The advanced BA group had significantly higher BMI SDS, DHEAS SDS, IGF-1 SDS, androstenedione and serum fasting insulin and significantly lower sex hormone binding globulin (all p<0.001). IGF-1 SDS (OR=1.642, p＜0.001) and DHEAS SDS (OR=1.125, p=0.021) were independent risk factors for advanced BA. In the multiple linear regression model, IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 18.9% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n=237 ), overweight (19.15%, n=81) and obesity (24.82%, n=105). The proportion of BA advancement in obesity was significantly higher than that of normal weight (χ2=18.088, P＜0.001). In a subgroup with normal weight, higher IGF-1 SDS (p=0.009) and DHEAS SDS (p=0.003) affect BA advancement independent of BMI SDS. Conclusions: Chinese girls aged 4-8 years with IPT requiring further investigations might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.