Physiological regulation of FGF-23 by dietary phosphate

描述（由申请人提供）：X连锁低磷血症性佝偻病、常染色体显性低磷血症性佝偻病和致癌性骨软化症的特征为磷酸盐尿，不能根据已知的磷酸盐稳态调节剂来解释。来自这3种临床疾病的数据表明，成纤维细胞生长因子23（FGF-23）是一种磷酸尿激素。这项为期12天的研究的目的是确定膳食磷酸盐操作对FGF-23水平的影响。将60名健康男性和女性志愿者随机分配至：第1组，低膳食磷酸盐摄入量，通过补充Amphogel实现;或第2组，高膳食磷酸盐摄入量，通过补充Neutrapos实现。蛋白质、钠、钙和热量的摄入将保持不变。FGF-23，血和尿磷酸盐，以及其他已知影响磷酸盐水平的激素将每天和两个24小时入院期间进行评估。我们假设高膳食磷酸盐会刺激FGF-23水平，而低膳食磷酸盐会抑制FGF-23水平。我们预计男性和女性参与者将表现出不同的生理机能。最后，我们预计FGF-23会有一个昼夜变化，反映了磷酸盐的昼夜变化。

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.