Weber Thomas J, Liu Shiguang, Indridason Olafur S, Quarles L Darryl
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Bone Miner Res. 2003 Jul;18(7):1227-34. doi: 10.1359/jbmr.2003.18.7.1227.
We investigated if the circulating levels of the phosphaturic factor FGF23 are elevated in subjects with XLH. Although we failed to find a statistically significant increase, FGF23 levels were significantly correlated with the degree of hypophosphatemia in XLH. In contrast, FGF23 levels were markedly increased in subjects with ESRD and correlated inversely with the degree of hyperphosphatemia.
Inactivating mutations of PHEX cause renal phosphate wasting in X-linked hypophosphatemic rickets (XLH) because of the accumulation of a phosphaturic hormone called phosphatonin. The recent discovery that FGF23 is the circulating phosphaturic factor in autosomal dominant hypophosphatemia raises the possibility that FGF23 is phosphatonin.
Fasting serum FGF23 levels and serum biochemical parameters were measured using a human FGF23 (C-terminal) ELISA assay in 11 subjects with XLH and 42 age-matched controls, 5 subjects with hypophosphatemia of unknown cause, and 14 hyperphosphatemic subjects with end stage renal disease (ESRD). Associations between variables were examined using the Spearman's correlation coefficient and linear regression analysis.
FGF23 (RU/ml) concentrations were not different (p = 0.11) between control and hypophosphatemic XLH subjects, but were significantly increased in hyperphosphatemic subjects with ESRD (p < 0.001). Western blot analysis found the presence of both full-length and C-terminal FGF23 fragments in serum from ESRD subjects. There was a strong inverse correlation between FGF23 and serum phosphorus (r = -0.60) and calcium and phosphorus (Ca x P) product (r = -0.65) in XLH, and a strong positive relationship between FGF23 and Pi (r = 0.50) and Ca x P product (r = 0.62) in ESRD. FGF23 levels were variably elevated in subjects with hypophosphatemia of unknown cause, one of which had tumor-induced osteomalacia (TIO). Removal of the tumor resulted in rapid reduction in serum FGF23 levels. These findings suggest that FGF23 has a possible role in mediating hypophosphatemia in XLH and TIO, but the overlapping levels of FGF23 in hypophosphatemic disorders and normal subjects indicate that serum phosphorus and FGF23 can also be independently regulated.
我们研究了X连锁低磷血症（XLH）患者中磷调节因子FGF23的循环水平是否升高。尽管我们未能发现有统计学意义的升高，但FGF23水平与XLH患者的低磷血症程度显著相关。相比之下，终末期肾病（ESRD）患者的FGF23水平显著升高，且与高磷血症程度呈负相关。
PHEX基因的失活突变导致X连锁低磷性佝偻病（XLH）患者出现肾性磷 wasting，原因是一种称为磷调节素的磷调节激素积累。最近发现FGF23是常染色体显性低磷血症中的循环磷调节因子，这增加了FGF23是磷调节素的可能性。
使用人FGF23（C末端）ELISA检测法，对11例XLH患者、42例年龄匹配的对照、5例病因不明的低磷血症患者和14例终末期肾病（ESRD）的高磷血症患者，测量空腹血清FGF23水平和血清生化参数。使用Spearman相关系数和线性回归分析检查变量之间的关联。
对照和低磷血症XLH患者之间的FGF23（RU/ml）浓度无差异（p = 0.11），但ESRD的高磷血症患者中显著升高（p < 0.001）。蛋白质印迹分析发现ESRD患者血清中存在全长和C末端FGF23片段。在XLH中，FGF23与血清磷（r = -0.60）以及钙磷（Ca×P）乘积（r = -0.65）之间存在强烈的负相关，而在ESRD中，FGF23与磷（r = 0.50）以及Ca×P乘积（r = 0.62）之间存在强烈的正相关。病因不明的低磷血症患者中FGF23水平有不同程度升高，其中1例患有肿瘤诱导的骨软化症（TIO）。切除肿瘤导致血清FGF23水平迅速降低。这些发现表明FGF23在介导XLH和TIO中的低磷血症方面可能起作用，但低磷血症疾病和正常受试者中FGF23水平的重叠表明血清磷和FGF23也可以独立调节。
