FGF23 Is Not Associated With Age-Related Changes in Phosphate, but Enhances Renal Calcium Reabsorption in Girls

Abstract

Context: Fibroblast growth factor (FGF)23 is a critical determinant of phosphate homeostasis. The role of FGF23, however, in regulating physiologic changes in serum phosphate and renal phosphate handling across childhood is not well described. In addition, animal models have suggested a role for FGF23 in regulating renal calcium excretion.

Objective: To assess changes in FGF23 concentrations across childhood in relation to changes in mineral ions and hormones of mineral ion homeostasis.

Design: This was a cross-sectional study.

Setting: The study was conducted at a Clinical Research Center at a tertiary care hospital.

Patients or other participants: Ninety healthy girls ages 9 to 18 years were recruited from the surrounding community.

Main outcome measures: The associations of intact and C-terminal FGF23 concentrations with measures of mineral ion homeostasis were determined by univariable and multivariable linear regression.

Results: Serum phosphate and renal phosphate excretion varied with age, as expected (R = -0.49, P < 0.001 and R = -0.48, P < 0.001, respectively). Neither intact nor C-terminal FGF23 varied with age, and FGF23 was not correlated with serum or urinary phosphate. Intact FGF23 was positively correlated with serum calcium (R = 0.39, P < 0.001) and negatively correlated with urinary calcium/creatinine ratio (R = -0.27, P = 0.011).

Conclusions: The changes in serum and urinary phosphate handling across childhood do not appear to be determined by alterations in FGF23 concentrations. These data may point to a role for FGF23 in calcium regulation in human physiology.

Trial registration: ClinicalTrials.gov NCT01180946.

Copyright © 2017 by the Endocrine Society

Figures

Figure 1.

Scatterplots showing correlations of (a) serum phosphate with age, (b) TP/GFR with age, (c) intact FGF23 with age, (d) C-terminal FGF23 with age, (e) intact FGF23 with serum phosphate, and (f) intact FGF23 with TP/GFR. PO4, phosphate.

Figure 2.

Scatterplots showing correlations of (a) intact FGF23 with 25-hydroxyvitamin D, (b) intact FGF23 with 1,25-dihydroxy-vitamin D, (c) intact FGF23 with serum calcium, and (d) intact FGF23 with the urinary calcium/creatinine ratio.

Figure 3.

Proposed model of FGF23 interactions with calcium and modulators of calcium homeostasis. FGF23 and 1,25(OH)2D interact in a previously described feedback loop in which 1,25(OH)2D stimulates FGF23, and FGF23 reduces 1,25(OH)2D levels by inhibiting CYP27B1 and stimulating CYP24A1 activity (solid lines). Data from this cohort suggest that FGF23 and serum calcium may also interact in an indirect feedback loop, in which increased serum calcium stimulates FGF23, thereby inhibiting 1,25(OH)2D synthesis, decreasing dietary calcium absorption, and thus decreasing serum calcium (dashed lines). In addition, the effect of FGF23 to enhance urinary calcium reabsorption, thereby decreasing urinary calcium excretion and increasing serum calcium, counters the effect of FGF23 to diminish 1,25(OH)2D-mediated dietary calcium absorption, and thus works to maintain serum calcium stability.