Reference intervals for intact FGF 23 in healthy Korean adults: lower concentrations in young adulthood require...

Fibroblast growth factor 23 (FGF23) is a bone-derived phosphaturic hormone that is essential for phosphate homeostasis. Elevated FGF23 levels underlie FGF23-related hypophosphatemic rickets and tumor-induced osteomalacia. Despite its clinical importance, population-based reference intervals (RIs) for intact FGF23 using the widely deployed LIAISON XL automated chemiluminescent immunoassay platform (DiaSorin) are lacking for East Asian populations.

We established method-specific RIs for intact FGF23 (iFGF23) in 386 healthy Korean adults (193 males and 193 females; age, 20-79 years) following the Clinical and Laboratory Standards Institute EP28-A3c guidelines. After the Box-Cox transformation and Horn's outlier detection, the RIs were derived using nonparametric methods (2.5th-97.5th percentiles). The necessity for partitioning was assessed using the Harris-Boyd method. Associations between iFGF23 levels and demographic, anthropometric, and biochemical parameters were examined using Pearson's correlation coefficients.

The overall nonparametric RI was 28.04-100.33 pg/mL (90% CI: 25.77-31.91 to 96.29-109.20). Age emerged as the primary determinant requiring partitioning, with young adults (20-29 years) exhibiting significantly lower concentrations than older adults (≥30 years): 25.73-78.76 versus 32.01-107.00 pg/mL. A sex-stratified analysis confirmed that this age effect persisted independently in both males and females. Although males had higher median iFGF23 than females (65.03 vs. 51.98 pg/mL, p < 0.001), Harris-Boyd analysis did not support sex-based partitioning (z = 5.17, z* = 5.38). Intact FGF23 was significantly correlated with age (r = 0.278), estimated glomerular filtration rate (r = -0.254), and alkaline phosphatase (r = 0.143; all p ≤ 0.005), but not with traditional mineral metabolism parameters (phosphate, calcium, parathyroid hormone, and 25-hydroxyvitamin D).

This study provides the first population- and method-specific RIs for intact FGF23 in an East Asian population and establishes critical age-stratified benchmarks for clinical interpretation. The distinct RI in young adults underscores the necessity of age-appropriate reference standards for diagnosing and monitoring phosphate homeostasis disorders. These findings highlight the importance of population-specific reference data in the absence of assay harmonization.