Hypophosphatemia after intravenous iron therapy: Comprehensive review of clinical findings and recommendations for management

Bone. 2022 Jan:154:116202. doi: 10.1016/j.bone.2021.116202. Epub 2021 Sep 15.


Contemporary intravenous iron formulations allow administration of high doses of elemental iron and enable correction of total iron deficit in one or two infusions. An important but underappreciated complication of certain formulations is hypophosphatemia caused by increased secretion of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). The pathophysiology of FGF23-induced hypophosphatemia due to certain intravenous iron formulations has been recently investigated in prospective clinical trials. To reach the correct diagnosis, clinicians must recognize the typical clinical manifestations of intravenous iron-induced hypophosphatemia and identify a specific pattern of biochemical changes (hyperphosphaturic hypophosphatemia triggered by high FGF23 that causes low 1,25 (OH)2 vitamin D, hypocalcemia and secondary hyperparathyroidism). Physicians and patients should be aware of hypophosphatemia as a common complication of intravenous iron therapy and monitor serum phosphate concentrations in patients receiving repeated doses of specific intravenous iron formulations. Symptoms of hypophosphatemia are associated with severity and duration. Persistent hypophosphatemia can occur with iron therapy and can cause debilitating diseases including myopathy, osteomalacia and fractures. This review summarizes the current understanding of the iron-phosphate axis as well as complications of intravenous iron-induced hypophosphatemia.

Keywords: FGF23; Ferric carboxymaltose; Ferric derisomaltose; Osteomalacia; Secondary hyperparathyreodism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia, Iron-Deficiency* / complications
  • Anemia, Iron-Deficiency* / drug therapy
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Hypophosphatemia* / chemically induced
  • Hypophosphatemia* / complications
  • Iron / adverse effects
  • Osteomalacia* / complications
  • Prospective Studies


  • Fibroblast Growth Factors
  • Iron