Fibroblast Growth Factor-23 Is Regulated by 1α,25-Dihydroxyvitamin D

Collins, Michael T.; Lindsay, John R.; Jain, Anuj; Kelly, Marilyn H.; Cutler, Carolee M.; Weinstein, Lee S.; Liu, Jie; Fedarko, Neal S.; Winer, Karen K.

doi:10.1359/jbmr.050718

Cited by 91 publications

(83 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although F e PO 4 increased within the VIT-D group, there were no between-group differences in F e PO 4 , serum phosphate, PTH, or calcium levels. Prior studies have shown that 1,25(OH) 2 D increases FGF23 synthesis and its circulating levels (13,14,25). This study is the first to show that ergocalciferol administration is associated with increased FGF23 production; however, in this model, we were unable to determine if the increase was because of ergocalciferol, 25OHD, or 1,25(OH) 2 D.…”

Section: Discussioncontrasting

confidence: 56%

See 1 more Smart Citation

Randomized Trial Assessing the Effects of Ergocalciferol Administration on Circulating FGF23

Burnett-Bowie

Leder

Henao

et al. 2012

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

SummaryBackground 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 1867 to 40612 ng/ml at week 4 (P,0.0001) and remained stable at 43612 ng/ml at week 12 (P,0.0001); 1,25-dihydroxyvitamin D increased from 42617 to 52618 pg/ml at week 4 (P,0.001) and then remained stable, and fibroblast growth factor 23 increased from 43617 to 60633 pg/ml at week 8 (P=0.001) and 74642 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.

show abstract

Section: Discussioncontrasting

confidence: 56%

“…1,25-Dihydroxyvitamin D [1,25(OH) 2 D], dietary phosphate, and circulating phosphate are key regulators of FGF23 (12)(13)(14)(15)(16)(17)(18). However, it is unknown if vitamin D (either ergocalciferol or cholecalciferol) affects FGF23 secretion.…”

Section: Introductionmentioning

confidence: 99%

Randomized Trial Assessing the Effects of Ergocalciferol Administration on Circulating FGF23

Burnett-Bowie

Leder

Henao

et al. 2012

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Concerning humans, there are data that correlate calcitriol with FGF23 in patients with renal impairment (17) and in patients with hypoparathyroidism (18), while data relating calcitriol with FGF23 in healthy individuals do not exist as far as we are aware.…”

mentioning

confidence: 95%

Effect of Calcitriol on FGF23 Level in Healthy Adults and its Dependence on Phosphate Level

Georgiadou

Marketou

Trovas

et al. 2017

View full text Add to dashboard Cite

Abstract. Aim: To evaluate the short-term effects of calcitriol and sevelamer hydrochloride on fibroblast growth factor-23 (FGF23) in humans and to determine whether the effect is direct or indirect through calcitriol-induced increased absorption of phosphorus from the intestine. Patients andFibroblast growth factor-23 (FGF23) is a circulating factor that plays an important role in the regulation of phosphate and vitamin D (1-3). FGF23 is produced by mature osteoblasts and osteocytes (2) and acts through FGF receptor-Klotho complexes in cell membranes. The kidney is the major target for FGF23; in the proximal renal tubule, FGF23 acts to promote phosphaturia by down-regulating the expression of luminal sodium-dependent phosphate transporters and to reduce synthesis of 1,25-dihydroxyvitamin D by downregulating 1a-hydroxylase and up-regulating 24-hydroxylase activity (4-6).Although the control of FGF23 production remains poorly understood, a complex interplay between systemic and local factors allows the coordination of bone buffering capacity with renal phosphate handling. The primary systemic factors that stimulate FGF23 secretion appear to be calcitriol and increased dietary phosphorus intake. Moreover the FGF23 level is directly correlated with serum parathyroid hormone (PTH), calcium, and phosphate level in uremic patients who are on maintenance hemodialysis (7-9).There is evidence that the plasma FGF23 level is regulated or affected by dietary phosphate. Recently, dietary consumption of phosphate was shown to increase serum FGF23 level in both uremic rats and non-uremic mice (10-12). In healthy individuals, increased dietary phosphate load has been reported to increase the serum level of FGF23 (13-16).In addition, calcitriol was shown to up-regulate serum FGF23 level in mice and in parathyroidectomized rats without a corresponding increase in serum phosphate level 145

show abstract

“…[17][18][19] In addition, FGF-23 is positively regulated by 1,25(OH) 2 D, PTH, and Klotho. [20][21][22] This complexity of the PO4-FGF-23 cybernetic system, coupled with the indeterminate evidence for an FGF-23 response to phosphate loads in humans, makes it difficult to predict the relative importance of these four hormones and the temporal relation of their response in the elimination of a PO4 load.…”

mentioning

confidence: 99%

The Human Response to Acute Enteral and Parenteral Phosphate Loads

Scanni

vonRotz

Jehle

et al. 2014

Journal of the American Society of Nephrology

104

View full text Add to dashboard Cite

The human response to acute phosphate (PO4) loading is poorly characterized, and it is unknown whether an intestinal phosphate sensor mechanism exists. Here, we characterized the human mineral and endocrine response to parenteral and duodenal acute phosphate loads. Healthy human participants underwent 36 hours of intravenous (IV; 1.15 [low dose] and 2.30 [high dose] mmol of PO4/kg per 24 hours) or duodenal (1.53 mmol of PO4/kg per 24 hours) neutral sodium PO4 loading. Control experiments used equimolar NaCl loads. Maximum PO4 urinary excretory responses occurred between 12 and 24 hours and were similar for low-dose IV and duodenal infusion. Hyperphosphatemic responses were also temporally and quantitatively similar for low-dose IV and duodenal PO4 infusion. Fractional renal PO4 clearance increased approximately 6-fold (high-dose IV group) and 4-fold (low-dose IV and duodenal groups), and significant reductions in plasma PO4 concentrations relative to peak values occurred by 36 hours, despite persistent PO4 loading. After cessation of loading, frank hypophosphatemia occurred. The earliest phosphaturic response occurred after plasma PO4 and parathyroid hormone concentrations increased. Plasma fibroblast growth factor-23 concentration increased after the onset of phosphaturia, followed by a decrease in plasma 1,25(OH)2D levels; a-Klotho levels did not change. Contrary to results in rodents, we found no evidence for intestinal-specific phosphaturic control mechanisms in humans. Complete urinary phosphate recovery in the IV loading groups provides evidence against any important extrarenal response to acute PO4 loads. Plasma phosphate (PO4) concentration is regulated within narrow limits and is the result of intestinal absorption, influx into and efflux from bone, renal excretion, and modest intestinal secretion. 1 Rapid changes in transcellular distribution are effected primarily by systemic acid-base equilibrium and hormones such as insulin and catecholamines. 2 1,25(OH) 2 D stimulates intestinal PO4 absorption, 4 while parathyroid hormone (PTH) and osteocytederived fibroblast growth factor-23 (FGF-23) are the best-characterized phosphaturic factors. Both inhibit proximal tubular sodium-dependent PO4 reabsorption (via Na/PO4 cotransport, NaPi2a and NaPi2c). 5,6 In addition, a-Klotho is a renal transmembrane and secreted protein that functions as an FGF-23 coreceptor and is phosphaturic independently of However, the relative roles of other phosphaturic agents, such as secreted frizzled related protein (sFRP-4), matrix extracellular phosphoglycoprotein, and FGF-8 are not yet defined in humans.1,25(OH) 2 D, PTH, and FGF-23 regulate PO4 metabolism within a complex system of positive and negative feedback mechanisms (for review, see Bergwitz and Jüppner 8 ). Increases in plasma PO4 concentration stimulate PTH secretion, while proximal tubule 1a-hydroxylase and, therefore,

show abstract

Fibroblast Growth Factor-23 Is Regulated by 1α,25-Dihydroxyvitamin D

Cited by 91 publications

References 37 publications

Randomized Trial Assessing the Effects of Ergocalciferol Administration on Circulating FGF23

Randomized Trial Assessing the Effects of Ergocalciferol Administration on Circulating FGF23

Effect of Calcitriol on FGF23 Level in Healthy Adults and its Dependence on Phosphate Level

The Human Response to Acute Enteral and Parenteral Phosphate Loads

Contact Info

Product

Resources

About