Phosphate homeostasis in pediatrics: The pubertal transition to tighter hormonal control

Phosphate homeostasis is crucial for pediatric growth, regulated by a complex endocrine network involving PTH, FGF23, Klotho, vitamin D metabolites, and growth factors like IGF-1. The specific impact of pubertal transition on the integration and sensitivity of these phosphate regulatory factors remains poorly defined. We hypothesize that puberty involves a reorganization of the hormonal control of phosphate handling.

This study analyzed data from 158 healthy Greek children (108 prepubertal, 50 pubertal). Hormonal and biochemical parameters measured included serum phosphate, urinary phosphate, PTH, 25-(OH) D, 1,25-(OH)₂D, IGF-1, soluble Klotho, and both intact and C-terminal forms of FGF23. Statistical analysis compared groups using t-tests and non-parametric equivalents and employed correlation analysis of prepubertal and pubertal matrices to explore and visualize the interactions of the regulatory factors before and after initiation of puberty.

Significant differences were observed between prepubertal and pubertal children in the network of correlations among hormones that regulate phosphate homeostasis including Klotho, PTH, vitamin D metabolites, iFGF23, cFCG23 and IGF-1. Prepubertally, few significant hormonal-phosphate correlations were present. During puberty, the network became denser, characterized by strong associations involving Klotho, iFGF23, cFGF23, PTH, 1,25-(OH)₂ D, ALP, and renal phosphate reabsorption indices (TmPO/GFR). Sex did not significantly modify these hormone interactions.

The pubertal status-based exploratory correlation matrix analysis indicates a substantial reorganization of the phosphate regulatory hormonal network. This transition moves control from a relatively sparse, less integrated system in prepubertal children toward a tightly coupled, more interconnected network involving Klotho, the FGF23 axis, and PTH/Vitamin D, likely reflecting the increased skeletal demand of adolescence. The findings underscore the need for further research in understanding the role of pubertal transition in phosphate metabolism.