Department of Pediatrics, Osaka Hospital, Japan Community Healthcare Organization (JCHO), Osaka, Japan.
J Pediatr Endocrinol Metab. 2021 Apr 12;34(6):791-798. doi: 10.1515/jpem-2020-0734. Print 2021 Jun 25.
X-linked hypophosphatemic rickets (XLH) is a congenital fibroblast growth factor (FGF)23-related metabolic bone disease that is treated with active vitamin D and phosphate as conventional therapies. Complications of these therapies include nephrocalcinosis (NC) caused by excessive urine calcium and phosphate concentrations. Recently, an anti-FGF23 antibody, burosumab, was developed and reported to be effective in poorly-controlled or severe XLH patients. This study aimed to reveal the impact of switching treatments in relatively well-controlled XLH children with the Rickets Severity Scale less than 2.0.
The effects of the two treatments in eight relatively well-controlled XLH children with a mean age of 10.4 ± 1.9 years were compared retrospectively for the same treatment duration (31 ± 11 months) before and after the baseline.
Actual doses of alfacalcidol and phosphate as conventional therapy were 150.9 ± 43.9 ng/kg and 27.5 ± 6.3 mg/kg per day, respectively. Renal echography revealed spotty NC in 8/8 patients, but no aggravation of NC was detected by switching treatments. Switching treatments increased TmP/GFR (p=0.002) and %TRP (p<0.001), and improved the high urine calcium/creatinine ratio to the normal range (p<0.001) although both treatments controlled disease markers equally. Additionally, low intact parathyroid hormone during conventional therapy was increased within the normal range by switching treatments.
Our results suggest that a high dose of alfacalcidol was needed to control the disease, but it caused hypercalciuria and NC. We concluded that switching treatments in relatively well-controlled XLH children improved renal phosphate reabsorption and decreased urine calcium extraction, and may have the potential to prevent NC.
X 连锁低磷血症性佝偻病（XLH）是一种先天性成纤维细胞生长因子（FGF）23 相关代谢性骨病，采用活性维生素 D 和磷酸盐进行常规治疗。这些治疗的并发症包括因尿钙和磷酸盐浓度过高而导致的肾钙质沉着症（NC）。最近，一种抗 FGF23 抗体布罗索尤单抗被开发出来，并被报道对控制不佳或严重 XLH 患者有效。本研究旨在揭示在佝偻病严重程度评分小于 2.0 的相对控制良好的 XLH 儿童中切换治疗的影响。
回顾性比较了 8 名年龄为 10.4±1.9 岁的相对控制良好的 XLH 儿童在基线前后相同治疗时间（31±11 个月）下两种治疗的效果。
常规治疗中阿法骨化醇和磷酸盐的实际剂量分别为 150.9±43.9ng/kg 和 27.5±6.3mg/kg/天。肾脏超声显示 8/8 例点状 NC，但切换治疗未发现 NC 加重。切换治疗增加了 TmP/GFR（p=0.002）和 %TRP（p<0.001），并将高尿钙/肌酐比值改善至正常范围（p<0.001），尽管两种治疗均能同等控制疾病标志物。此外，常规治疗中低完整甲状旁腺激素在切换治疗后增加至正常范围内。
我们的结果表明，需要高剂量的阿法骨化醇来控制疾病，但它会导致高钙尿症和 NC。我们得出结论，在相对控制良好的 XLH 儿童中切换治疗可改善肾脏磷酸盐重吸收并减少尿钙提取，可能具有预防 NC 的潜力。
