Christian Doppler Laboratory of Iron and Phosphate Biology at the Department of Medicine I, Medical University of Innsbruck, Innsbruck, Austria.
Division of Nephrology, Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
J Clin Endocrinol Metab. 2022 Mar 24;107(4):1009-1019. doi: 10.1210/clinem/dgab852.
Hypophosphatemia, osteomalacia, and fractures are complications of certain intravenous iron formulations.
This study investigated risk factors for incident, severe, and persistent hypophosphatemia, and associated alterations in bone and mineral biomarkers following intravenous iron treatment.
We analyzed data from the PHOSPHARE-IDA randomized clinical trials, comprising 245 patients aged 18 years or older with iron deficiency anemia at 30 outpatient clinics in the United States who received intravenous ferric carboxymaltose (FCM) or ferric derisomaltose (FDI). Outcome measures included serum phosphate, intact fibroblast growth factor-23 (iFGF23), 1,25-dihydroxyvitamin D (1,25(OH)2D), ionized calcium, parathyroid hormone (PTH), and alkaline phosphatase.
FCM was the only consistent risk factor for incident hypophosphatemia (< 2.0 mg/dL; odds ratio vs FDI: 38.37; 95% CI: 16.62, 88.56; P < 0.001). Only FCM-treated patients developed severe hypophosphatemia (< 1.0 mg/dL; 11.3%; 13/115) or persistent hypophosphatemia (< 2.0 mg/dL at study end; 40.0%; 46/115). More severe hypophosphatemia associated with significantly greater increases in iFGF23, PTH, and alkaline phosphatase, and more severe decreases in 1,25(OH)2D and ionized calcium (all P < 0.05). Patients with persistent vs resolved hypophosphatemia demonstrated significantly greater changes in iFGF23, PTH, 1,25(OH)2D, and N-terminal procollagen-1 peptide levels (all P < 0.01), but alkaline phosphatase increased similarly in both groups.
Treatment with FCM was the only consistent risk factor for hypophosphatemia. Patients who developed severe or persistent hypophosphatemia after FCM treatment manifested more severe derangements in bone and mineral metabolism. Changes in bone biomarkers continued beyond resolution of hypophosphatemia, suggesting ongoing effects on bone that may help explain the association of FCM with osteomalacia and fractures.
低磷血症、骨软化症和骨折是某些静脉铁制剂的并发症。
本研究旨在调查静脉铁治疗后发生、严重和持续性低磷血症的危险因素，以及相关的骨和矿物质生物标志物的变化。
我们分析了来自 PHOSPHARE-IDA 随机临床试验的数据，该试验纳入了美国 30 家门诊诊所的 245 名年龄在 18 岁或以上的缺铁性贫血患者，他们接受了静脉羧基麦芽糖铁（FCM）或静脉去铁胺（FDI）治疗。主要结局指标包括血清磷、完整成纤维细胞生长因子-23（iFGF23）、1,25-二羟维生素 D（1,25(OH)2D）、离子钙、甲状旁腺激素（PTH）和碱性磷酸酶。
FCM 是唯一与新发低磷血症（<2.0mg/dL；FCM 与 FDI 相比的比值比：38.37；95%置信区间：16.62,88.56；P<0.001）相关的危险因素。只有 FCM 治疗的患者发生严重低磷血症（<1.0mg/dL；11.3%；13/115）或持续性低磷血症（<2.0mg/dL，研究结束时；40.0%；46/115）。更严重的低磷血症与 iFGF23、PTH 和碱性磷酸酶的显著增加以及 1,25(OH)2D 和离子钙的显著减少相关（所有 P<0.05）。与低磷血症缓解的患者相比，持续性低磷血症的患者 iFGF23、PTH、1,25(OH)2D 和 N 端前胶原 1 肽水平的变化明显更大（所有 P<0.01），但两组碱性磷酸酶的增加相似。
FCM 治疗是低磷血症的唯一一致危险因素。FCM 治疗后发生严重或持续性低磷血症的患者表现出更严重的骨和矿物质代谢紊乱。骨生物标志物的变化在低磷血症缓解后仍在继续，这表明对骨骼的持续影响可能有助于解释 FCM 与骨软化症和骨折的关联。
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