Age-specific centiles for fibroblast growth factor 23 and its associations with mineral and bone metabolism in healthy children

BACKGROUND: Fibroblast Growth Factor 23 (FGF23) regulates phosphate and vitamin D metabolism and is implicated in pediatric disorders such as X-linked hypophosphatemia and CKD-mineral and bone disorder. Accurate interpretation in children requires age-adjusted centile charts. OBJECTIVE: To construct age- and sex-specific centile charts for intact (iFGF23) and C-terminal (cFGF23) FGF23 in healthy UK children and examine associations with mineral and bone metabolism markers. METHODS: In a cross-sectional cohort of 430 children aged 0-16 years, plasma iFGF23 and cFGF23 were measured using DiaSorin and Quidel immunoassays. Age-specific centiles (2.5th-97.5th) were generated using GAMLSS modeling. Serum phosphate, albumin-adjusted calcium (AdCa), vitamin D metabolites, PTH, and bone turnover markers (PINP, CTX, NTX, BAP) were assessed. Associations were evaluated using LN-transformed regression and Pearson correlations. RESULTS: FGF23 concentrations declined with age, with highest values in infancy. At 2 years, median iFGF23 was 43.0 pg/mL (2.5-97.5th centiles: 20.8-81.6 pg/mL), while by 16 years, the median remained 42.9 pg/mL (20.8-81.5 pg/mL). For C-terminal FGF23 (cFGF23), the median was 98.2 RU/mL (2.5-97.5th centiles: 47.0-225.4 RU/mL) at 2 years and 80.2 RU/mL (38.4-184.1 RU/mL) at 16 years (p < 0.001). Correlation analyses showed weak but statistically significant associations of cFGF23 with PINP (r = 0.199, p < 0.001) and NTX (r = 0.150, p = 0.005), while iFGF23 exhibited similar weak correlations, with PINP (r = 0.120, p < 0.016) and BAP (r = 0.121, p = 0.013). CONCLUSION: We constructed age-specific centile charts for iFGF23 and cFGF23 in healthy children required for the interpretation of FGF23 in clinical practice and to provide a foundation for improved management of pediatric disorders in phosphate and vitamin D metabolism. Phosphate was the strongest predictor of both iFGF23 and cFGF23. Age and 25OHD predicted iFGF23 but not cFGF23. Both were correlated with markers of bone metabolism.