title: Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men.
abstract: 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.
authors.affiliation: Service of Bone Diseases, Geneva University Hospital, 24 rue Micheli-du-Crest, Geneva 1211, Switzerland. serge.ferrari@medecine.unige.ch
authors.forename: Serge L
authors.initials: SL
authors.lastname: Ferrari
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Bonjour
authors.forename: René
authors.initials: R
authors.lastname: Rizzoli
mesh_terms: 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*
chemical_list: 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