Increased bone mineral density and serum leptin in non-obese girls with precocious pubarche: Relation to low birthweight and hyperinsulinism

Background: Hyperinsulinism and hyperandrogenism have the capacity to incre ase bone mineral density (BMD) and serum leptin, independently of body fat mass. We therefore assessed lumbar BMD and serum leptin in girls with the s equence of a low birthweight and precocious pubarche (PP) in childhood, in whom hyperinsulinism and hyperandrogenism have been described. Methods: Fif ty-two non-obese PP girls were studied (age range 6.9-14.9 years). Serum le ptin was also measured in 42 control girls, matched for age, body mass inde x and pubertal stage. Results: BMD SDS, measured by dual-energy X-ray absor ptiometry, was elevated in PP girls compared to the population reference (0 .39 +/- 0.18 SDS; p = 0.03) and bone age, assessed from hand radiographs, w as significantly advanced compared to chronological age (1.2 +/- 0.1 years; p < 0.0005). Conclusion: Compared to control girls, PP girls had higher le ptin levels for degree of body mass index (PP girls: 9.4 +/- 0.6 ng/ml; con trols: 7.8 +/- 0.6 ng/ml; p = 0.01). In PP girls, serum leptin was inversel y related to birthweight (r = -0.32, p = 0.01) and positively related to fr ee androgen index (FAI) (r = 0.71, p < 0.0005). BMD SDS was also inversely related to birthweight (r = -0.26, p < 0.05) and positively related to seru m leptin (r = 0.42, p < 0.05), FAI (r = 0.45, p < 0.05) and mean serum insu lin during oral glucose tolerance testing (MSI) (r = 0.59, p < 0.0005). in multiple regression, MSI was the strongest determinant of BMD SDS (p = 0.50 , p = 0.002). In conclusion, elevated BMD and serum leptin in non-obese PP girls were related to degrees of low birthweight, hyperinsulinism and hyper androgenism. The characteristic hyperinsulinism of PP girls is proposed to be the key variable in this constellation. Copyright (C) 2001 S.Karger AG, Basel.