
FGF23 is a regulator of vitamin D metabolism and is associated with increased risk of vitamin D deficiency. Most management strategies for children with conditions associated with elevated FGF23 (such as X-linked hypophosphatemia) are based on studies in adults and reference ranges for FGF23 in children are limited. Due to skeletal growth, high bone turnover and pubertal changes, mineral homeostasis and their regulators differ from those in adults. Understanding FGF23 ranges and its regulatory factors in healthy children is required to enable FGF23 concentrations to be correctly interpreted and used in the management of paediatric conditions with elevated FGF23. Here we present references ranges (RR) for intact FGF23 (iFGF23, DiaSorin) and c-terminal FGF23 (cFGF23, Quidel) and their relationship with regulatory factors in a cohort of 488 children (62% males) aged 1-17 years from a single centre in East England, UK. Participants were classified by standard pubertal stages: infants (<1 year), pre-pubertal (Tanner stage 1), pubertal (Tanner stages 2 to 4), and post-pubertal (Tanner stage 5). BMI Standard Deviation Score (BMI-SDS) was used as covariate. 25-hydroxy and 1,25 di-hydroxy vitamin D (25OHD and 1,25(OH)2D) (LC-MS/MS), Phosphate, Albumin Adjusted Calcium (AdCa) and parathyroid hormone (PTH) (Cobas, Roche Diagnostics) were also analysed. RR between age groups were determined as the 2.5th and 97.5th percentiles and Kruskal-Wallis’s test used to compare groups. Predictors of FGF23 were analysed by multiple linear regression in SPSS. The RR for iFGF23 and cFGF23 by pubertal stage (Table) is given for sexes combined as sex was non-significant. We showed significantly higher concentrations in infants compared to older children. Significant predictors of iFGF23 were phosphate, pubertal age, 25OHD and AdCa, in univariate and multivariate models (r² = 7.3%, p < 0.001). Predictors of cFGF23 were phosphate and AdCa, in univariate and multivariate models (r² = 11.5%, p < 0.001). Standard pubertal ageIntact FGF23 (pg/mL)cFGF23 (RU/mL) Infants ≤11months$≤100 (n=12)≤318 (n=12) Pre-pubertal 22.5-71.5 a (n=269)44.5-185.5 a (n=259) Pubertal 22.5-66.3 a (n=108)42.7-148.6 a (n=107) Post-pubertal 19.6-78.2 a (n=68)48.5-202.8 a (n=65) $: Due to the limited number of infants, only the 90% percentile is given; a: Kruskal-Wallis with post-hoc test; significance at p<0.05 against infants. RR for iFGF23 and cFGF23 concentrations in children of all pubertal stages in this paediatric cohort exceeded typical adult ranges (22.7 to 93.1 pg/mL) for iFGF23 and <100 RU/mL for cFGF23) and may reflect higher phosphate concentrations found in childhood. The strong association with regulatory factors indicates that interpretations of FGF23 values should be considered in the context of other factors regulating mineral homeostasis. Establishing age-specific reference ranges and identifying key predictors lays the foundation for improved management of FGF23-related disorders in paediatric populations.