Physiological regulation of FGF-23 by dietary phosphate

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DESCRIPTION (provided by applicant): X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, and oncogenic ostcomalacia, are characterized by phosphaturia that cannot be explained on the basis of known regulators of phosphate homeostasis. Data from these 3 clinical disorders suggest that fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone. The goal of this 12-day study is to determine the effects of dietary phosphate manipulation on FGF-23 levels. 60 healthy male and female volunteers will be randomly assigned to: Group 1, low dietary phosphate intake, achieved with Amphogel supplementation; or Group 2, high dietary phosphate intake, achieved with Neutraphos supplementation. Protein, sodium, calcium and caloric intake will be kept constant. FGF-23, blood and urinary phosphate, and other hormones known to affect phosphate levels will be assessed daily and during two 24-hour admissions. We hypothesize that high dietary phosphate will stimulate FGF-23 levels, and low dietary phosphate will suppress FGF-23 levels. We anticipate that male and female participants will show different physiology. Finally, we anticipate that there will be a diurnal variation in FGF-23 that mirrors the diurnal variation in phosphate.