Randomized trial assessing the effects of ergocalciferol administration on circulating FGF23

Abstract

Background and objectives: Fibroblast growth factor 23 is a phosphate- and vitamin D-regulating hormone. The objective of this study was to determine the effect of ergocalciferol administration on fibroblast growth factor 23 levels in healthy vitamin D-deficient subjects.

Design, setting, participants, & measurements: In this 12-week trial conducted in a clinical research center, 18- to 45-year-old subjects (n=90) with 25-hydroxyvitamin D levels ≤20 ng/ml (by chemiluminescent immunoassay) were randomized to weekly ergocalciferol treatment of 50,000 international units or placebo, while consuming a self-selected diet. Changes in fibroblast growth factor 23, 25-hydroxyvitamin D (by liquid chromatography/tandem mass spectroscopy), 1,25-dihydroxyvitamin D, parathyroid hormone, and serum phosphate were measured.

Results: Mean 25-hydroxyvitamin D (P<0.0001), 1,25-dihydroxyvitamin D (P=0.01), and fibroblast growth factor 23 (P=0.003) increased in the treatment versus placebo group. In the treatment group, 25-hydroxyvitamin D increased from 18 ± 7 to 40 ± 12 ng/ml at week 4 (P<0.0001) and remained stable at 43 ± 12 ng/ml at week 12 (P<0.0001); 1,25-dihydroxyvitamin D increased from 42 ± 17 to 52 ± 18 pg/ml at week 4 (P<0.001) and then remained stable, and fibroblast growth factor 23 increased from 43 ± 17 to 60 ± 33 pg/ml at week 8 (P=0.001) and 74 ± 42 pg/ml at week 12 (P<0.0001). Urinary phosphate excretion increased within the treatment group, but parathyroid hormone and serum phosphate were unchanged.

Conclusions: Ergocalciferol administration increases circulating fibroblast growth factor 23. When measuring fibroblast growth factor 23, concurrent 25-hydroxyvitamin D measurements should be obtained, because vitamin D deficiency may lower circulating fibroblast growth factor 23 levels.

Figure 1.

Changes in 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D [1,25(OH)₂D], and fibroblast growth factor 23 (FGF23) with ergocalciferol administration. Mean (±SEM) of (A) 25OHD measured by liquid chromatography/tandem mass spectroscopy (the horizontal line represents the lower limit of normal), (B) 1,25(OH)₂D (the horizontal lines represent the normal range), and (C) FGF23 (the horizontal lines represent the normal range based on our prior data) at weeks 0, 4, 8, and 12 in the vitamin D (solid line) and placebo (dashed line) groups. P value assesses change over time by repeated-measures ANOVA compared with placebo. Systeme International conversion factors are 25OHD (nM), 2.496; and 1,25(OH)₂D (pmol/L), 2.6.

Figure 2.

Changes in fractional excretion of phosphate (F_ePO₄), phosphate, parathyroid hormone (PTH), and calcium with ergocalciferol administration. Mean (±SEM) of (A) F_ePO₄, (B) serum phosphate, (C) PTH, and (D) serum calcium at weeks 0, 4, 8, and 12 in the vitamin D (solid line) and placebo (dashed line) groups. The horizontal lines represent the normal range for the variables. None of the changes over time by repeated measures ANOVA compared with placebo were statistically significant. Systeme International conversion factors are serum phosphate (mM), 0.2495; PTH (ng/L), 1; and serum calcium (mM), 0.3229.