Physiological regulation of FGF-23 by dietary phosphate

描述(申请人提供)：X连锁低磷血症性软骨病，常染色体显性低磷血症性软骨病，以磷酸盐尿症为特征，不能用已知的磷酸盐稳态调节器来解释。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天的研究的目标是确定饮食中磷酸盐操作对成纤维细胞生长因子-23水平的影响。60名健康的男性和女性志愿者将被随机分配到：第一组，通过补充两性凝胶实现低饮食磷酸盐摄入量；或者第二组，通过补充Neutraphos实现高饮食磷酸盐摄入量。蛋白质、钠、钙和热量的摄入量将保持不变。每天和两次24小时入院期间将对成纤维细胞生长因子-23、血和尿磷酸盐以及其他已知影响磷酸盐水平的激素进行评估。我们假设高磷饮食会刺激成纤维细胞生长因子-23的水平，低磷饮食会抑制成纤维细胞生长因子-23的水平。我们预计，男性和女性参与者将表现出不同的生理特征。最后，我们预计成纤维细胞生长因子-23将会有一个反映磷酸盐日变化的日变化。

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.