Alon Uri S, Levy-Olomucki Rachel, Moore Wayne V, Stubbs Jason, Liu Shiguang, Quarles L Darryl
Pediatric Nephrology, Bone and Mineral Disorders Clinic, Children's Mercy Hospital, University of Missouri, Kansas City, MO 64108, USA.
Clin J Am Soc Nephrol. 2008 May;3(3):658-64. doi: 10.2215/CJN.04981107. Epub 2008 Feb 6.
The treatment for X-linked hypophosphatemia (XLH) with phosphate and calcitriol can be complicated by secondary hyperparathyroidism and nephrocalcinosis. Furthermore, vitamin D and phosphate stimulate FGF23 production, the pathogenic factor causing XLH. We investigated in XLH patients: 1) whether treatment with the calcimimetic agent, cinacalcet, will block the rise in parathyroid hormone (PTH) caused by phosphate administration; and 2) whether treatment with oral phosphate and calcitriol increases FGF23 levels.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Eight subjects with XLH were given a single oral dose of phosphate, followed the next day by combined treatment with phosphate and cinacalcet. Serum measurements of ionized calcium (Ca), phosphate, creatinine, intact PTH, 1,25(OH)(2)D, FGF23, and tubular threshold for phosphate/glomerular filtration rate (TP/GFR) were assessed in response to short-term treatment with phosphate and cinacalcet and compared with long-term administration of phosphate and calcitriol.
Oral phosphate load increased serum phosphate, decreased ionized calcium, and increased PTH. Twenty-four hours later, FGF23 significantly increased and 1,25(OH)(2)D decreased. The concomitant administration of phosphate and cinacalcet resulted in further decrease in serum Ca(2+) but suppression of PTH and greater increase in serum phosphate and TP/GFR. Chronic treatment with phosphate and calcitriol resulted in a smaller increment in serum phosphate and high serum FGF23.
Traditional therapy of XLH with phosphate and calcitriol elevates FGF23 and has the potential to stimulate PTH. Short-term treatment with cinacalcet suppresses PTH, leading to increase in TP/GFR and serum phosphate. Thus, long-term clinical studies are needed to investigate whether cinacalcet may be a useful adjuvant in the treatment of XLH, allowing the use of lower doses of phosphate and calcitriol.
用磷酸盐和骨化三醇治疗X连锁低磷血症（XLH）可能会并发继发性甲状旁腺功能亢进和肾钙质沉着症。此外，维生素D和磷酸盐会刺激成纤维细胞生长因子23（FGF23）的产生，而FGF23是导致XLH的致病因素。我们对XLH患者进行了研究：1）拟钙剂西那卡塞治疗是否会阻止因给予磷酸盐而导致的甲状旁腺激素（PTH）升高；2）口服磷酸盐和骨化三醇治疗是否会增加FGF23水平。
设计、地点、参与者与测量方法：8名XLH患者单次口服一剂磷酸盐，次日给予磷酸盐和西那卡塞联合治疗。评估短期给予磷酸盐和西那卡塞治疗后血清中离子钙（Ca）、磷酸盐、肌酐、完整PTH、1,25(OH)₂D、FGF23以及磷酸盐/肾小球滤过率肾小管阈值（TP/GFR）的测量值，并与长期给予磷酸盐和骨化三醇治疗进行比较。
口服磷酸盐负荷使血清磷酸盐升高，离子钙降低，PTH升高。24小时后，FGF23显著升高，1,25(OH)₂D降低。同时给予磷酸盐和西那卡塞导致血清Ca²⁺进一步降低，但PTH受到抑制，血清磷酸盐和TP/GFR升高幅度更大。长期用磷酸盐和骨化三醇治疗导致血清磷酸盐升高幅度较小，血清FGF23升高。
传统的XLH治疗方法，即使用磷酸盐和骨化三醇，会升高FGF23并有可能刺激PTH。短期使用西那卡塞治疗可抑制PTH，导致TP/GFR和血清磷酸盐升高。因此，需要进行长期临床研究，以调查西那卡塞是否可能是治疗XLH的有用辅助药物，从而允许使用更低剂量的磷酸盐和骨化三醇。
