Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men.
The renal handling of inorganic phosphate (Pi) is controlled not only by PTH, but also by hitherto undetermined mechanisms dependent on phosphate intake. Recently, fibroblast growth factor (FGF)-23 was identified as a novel phosphaturic factor in tumor-induced osteomalacia and autosomal-dominant hypophosphatemic rickets. We hypothesized that phosphate intake could influence FGF-23 concomitantly to the changes in renal Pi handling. Twenty-nine healthy males were subjected to a 5-d low-phosphate diet and a phosphate binder, followed by a high-phosphate diet including supplements. Concomitant modifications in calcium intake allowed minimizing PTH changes in response to dietary phosphate. Serum FGF-23 levels significantly decreased on the low-phosphate diet, then increased with the oral phosphate load. Changes in FGF-23 were positively correlated with changes in 24-h urinary Pi excretion and negatively correlated with changes in the maximal tubular reabsorption of Pi and 1,25(OH)(2)D(3) (calcitriol), whereas PTH was not. In multivariate analysis, changes in FGF-23 remained the most significantly correlated to changes in 1,25(OH)(2)D(3) and maximal tubular reabsorption of Pi. Moreover, FGF-23 was positively correlated to serum osteocalcin, a marker of osteoblastic activity. In summary, FGF-23 was inversely related to renal Pi transport and serum calcitriol levels in healthy young men. These data suggest that FGF-23 may be implicated in the physiological regulation of Pi homeostasis in response to dietary phosphate changes, independent of PTH.
Ferrari
Serge L
SL
Service of Bone Diseases, Geneva University Hospital, 24 rue Micheli-du-Crest, Geneva 1211, Switzerland. serge.ferrari@medecine.unige.ch
Bonjour
Jean-Philippe
JP
Rizzoli
René
R
D000328:Adult; D002117:Calcitriol / Q000097:blood; D002136:Calcium, Dietary / Q000493:pharmacokinetics; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000652:urine*; D016226:Phosphorus, Dietary / Q000493:pharmacokinetics*
D002136:Calcium, Dietary; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D016226:Phosphorus, Dietary; D015675:Osteocalcin; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol