Bone age advancement in prepubertal children with obesity and premature adrenarche: possible potentiating factors

Abstract

Obesity and premature adrenarche (PA) are both associated with bone age (BA) advancement of unclear etiology, which may lead to earlier puberty, suboptimal final height and obesity in adulthood. Our objective was to understand the hormonal and anthropometric characteristics of BA advancement in a spectrum of prepubertal children with and without obesity and PA. In this cross-sectional study of 66 prepubertal children (35 PA, 31 control, 5-9 years), BMI z-score, hormonal values and response to an oral glucose tolerance test were the main outcome measures. Subjects were divided into tertiles by BA divided by chronological age (BA/CA), an index of BA advancement. Subjects in the top tertile for BA/CA had the highest dehydroepiandrosterone sulfate (DHEAS), free testosterone (%), hemoglobin A(1C), BMI z-score, and weight (P < 0.05). BMI z-score (r = 0.47), weight (r = 0.40), free testosterone (%) (r = 0.34), and DHEAS (r = 0.30) correlated with BA/CA (P < 0.02). Regression analysis showed greater BA/CA in PA compared to controls after controlling for weight (0.21 ± 0.56, P < 0.004). An exploratory stepwise regression model showed that weight, estradiol, and DHEAS were the strongest predictors of BA/CA accounting for 24% of its variance. Obesity was highly associated with BA advancement in this study of prepubertal children. In addition, children with PA had greater BA/CA at any given weight when compared to controls. These findings suggest a possible hormonal factor, which potentiates the effect of obesity on BA advancement in children with obesity and/or PA.

Figure 1

Tertile analysis of BA/CA. Each bar depicts mean value. a. Mean weight by tertile; b. Mean BMI z-score by tertile; c. Mean DHEAS by tertile; d. Mean free testosterone (%) by tertile. Horizontal lines represent differences and significance among the tertiles.

Figure 1

Tertile analysis of BA/CA. Each bar depicts mean value. a. Mean weight by tertile; b. Mean BMI z-score by tertile; c. Mean DHEAS by tertile; d. Mean free testosterone (%) by tertile. Horizontal lines represent differences and significance among the tertiles.

Figure 1

Tertile analysis of BA/CA. Each bar depicts mean value. a. Mean weight by tertile; b. Mean BMI z-score by tertile; c. Mean DHEAS by tertile; d. Mean free testosterone (%) by tertile. Horizontal lines represent differences and significance among the tertiles.

Figure 1

Tertile analysis of BA/CA. Each bar depicts mean value. a. Mean weight by tertile; b. Mean BMI z-score by tertile; c. Mean DHEAS by tertile; d. Mean free testosterone (%) by tertile. Horizontal lines represent differences and significance among the tertiles.

Figure 2

Linear regression of weight on BA/CA in PA (grey symbols, dotted line) and control (black symbols, solid line) subjects: PA (BA/CA = 0.90244 + (weight × 0.00700), p < 0.02); controls (BA/CA = 0.91345 + (weight × 0.00550), p < 0.03). PA subjects had higher BA/CA than control subjects after controlling for group differences in weight (p<0.004). The PA subjects also showed a statistically higher slope relating BA/CA to weight (0.325 ± 0.014) than control subjects (0.0294 ± 0.018), with an approximate 11% difference in the slopes of the two regression lines (p<0.01). Thus, for example, if a control and a PA subject both weigh 20 kg, then the predicted advancement of bone age in PA is 1.84% compared to control; in order to have the same BA/CA as a control subject, a PA subject would weigh only 17.3 kg (2.7 kg less than control). If a control and a PA subject both weigh 60 kg then the predicted advancement of bone age is 6.32%; in order to have the same BA/CA as a control subject, a PA subject would weigh only 48.8 kg (11.2 kg less than control).