Effects of hPTH(1-34) infusion on circulating serum phosphate, 1,25-dihydroxyvitamin D, and FGF23 levels in healthy men

Abstract

Fibroblast growth factor 23 (FGF23) promotes phosphaturia and suppresses 1,25-dihydroxyvitamin D [1,25(OH)(2)D] production. PTH also promotes phosphaturia, but, in contrast, stimulates 1,25(OH)(2)D production. The relationship between FGF23 and PTH is unclear, and the acute effect of pharmacologically dosed PTH on FGF23 secretion is unknown. Twenty healthy men were infused with human PTH(1-34) [hPTH(1-34)] at 44 ng/kg/h for 24 h. Compared with baseline, FGF23, 1,25(OH)(2)D, ionized calcium (iCa), and serum N-telopeptide (NTX) increased significantly over the 18-h hPTH(1-34) infusion (p < 0.0001), whereas serum phosphate (PO(4)) transiently increased and then returned to baseline. FGF23 increased from 35 +/- 10 pg/ml at baseline to 53 +/- 20 pg/ml at 18 h (p = 0.0002); 1,25(OH)(2)D increased from 36 +/- 16 pg/ml at baseline to 80 +/- 33 pg/ml at 18 h (p < 0.0001); iCa increased from 1.23 +/- 0.03 mM at baseline to 1.46 +/- 0.05 mM at hour 18 (p < 0.0001); and NTX increased from 17 +/- 4 nM BCE at baseline to 28 +/- 8 nM BCE at peak (p < 0.0001). PO(4) was 3.3 +/- 0.6 mg/dl at baseline, transiently rose to 3.7 +/- 0.4 mg/dl at hour 6 (p = 0.016), and then returned to 3.4 +/- 0.5 mg/dl at hour 12 (p = 0.651). hPTH(1-34) infusion increases endogenous 1,25(OH)(2)D and FGF23 within 18 h in healthy men. Whereas it is possible that the rise in PO(4) contributed to the observed increase in FGF23, the increase in 1,25(OH)(2)D was more substantial and longer sustained than the change in serum phosphate. Given prior data that suggest that neither PTH nor calcium stimulate FGF23 secretion, these data support the assertion that 1,25(OH)(2)D is a potent physiologic stimulator of FGF23 secretion.

Figures

FIG. 1

Mean (±SE) (A) ionized calcium, (B) 1,25-dihydroxyvitamin D, (C) serum phosphate, and (D) FGF23 at 0, 6, 12, and 18 h with hPTH(1-34) infusion. *p value assesses change over time by repeated-measures ANOVA compared with baseline. ns, not significant. Systeme International conversion factors: 1,25-dihydroxyvitamin D (pM), 2.6; phosphate (mM), 0.2495; and parathyroid hormone (ng/liter), 1.

FIG. 2

Individual data for (A) ionized calcium, (B) 1,25-dihydroxyvitamin D, (C) serum phosphate, and (D) FGF23 at 0 and 18 h with hPTH(1-34) infusion for subjects with hyperparathyroidism/vitamin D deficiency [PTH > 60 pg/ml and 25(OH)D n = 2) or PTH ≤ 60 pg/ml and 25(OH)D < 30 ng/ml (n = 8)] (□) vs. those with normal PTH and vitamin D levels [PTH < 60 pg/ml and 25(OH)D ≥ 30 ng/ml (n = 10)] (■). For each variable, the top panel shows the individual data and the bottom panel shows the mean (±SE) for the two groups. *p value assesses a between-group difference at either hour 0 or 18. Systeme International conversion factors: 25-hydroxyvitamin D (nM), 2.496, 1,25-dihydroxyvitamin D (pM), 2.6; phosphate (mM), 0.2495; and parathyroid hormone (ng/liter), 1.