The relationships between pubertal development, IGF-1 axis, and bone formation in healthy adolescents

As IGF-1 is the major factor that affects bone growth, and both osteocalcin and bone-specific alkaline phosphatase are important markers of bone formation during puberty, there must be a relationship between these markers that does not change according to sex. The aim of this study was to investigate the relationships between pubertal development, the IGF-1 axis, and bone formation in healthy adolescents. Two hundred and five healthy children and adolescents were included in this cross-sectional study. Tanner’s classification was used to determine the pubertal developmental stage. Serum IGF-1 levels and IGF-1/IGFBP-3 ratios increased with advancing pubertal stages, and maximum mean values were found at stages III–IV in girls and at stage IV in boys. Serum IGF-1 and IGFBP-3 levels were significantly correlated with osteocalcin and bone-specific alkaline phosphatase levels in boys, but not in girls. This difference between the sexes, and the relation of the IGF-1 axis to increased bone formation during puberty in both sexes, can be explained by the rate of increase of the IGF-1/IGFBP-3 ratio. We conclude that the timing of the increased bone formation rate during puberty; that is, the timing of the pubertal growth spurt, is determined by the maximum increase rate of the IGF-1/IGFBP-3 ratio. But this new hypothesis needs to be supported by longitudinal studies.