Aristeidis Giannakopoulos, Despoina Gkentzi, Alexandra Efthymiadou, Dionisios Chrysis
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.
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.