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

Bone

Volumn 154, Issue , 2022, Pages

  Schaefer, Benedikt ^a,b   Tobiasch, Moritz ^c   Wagner, Sonja ^a,b   Glodny, Bernhard ^a   Tilg, Herbert ^a   Wolf, Myles ^d   Zoller, Heinz ^a,b  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^b INSTITUTE FOR MICROELECTRONICS   (Austria)

^c Department for Psychiatry and Psychotherapy B   (Austria)

^d DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Ferric carboxymaltose; Ferric derisomaltose; FGF23; Osteomalacia; Secondary hyperparathyreodism

Indexed keywords

FERRIC CARBOXYMALTOSE; FERRIC PHOSPHATE; FIBROBLAST GROWTH FACTOR 23; IRON; FIBROBLAST GROWTH FACTOR;

HUMAN; HYPOCALCEMIA; HYPOPHOSPHATEMIA; IRON DEFICIENCY; IRON THERAPY; PHOSPHATE EXCRETION; PHOSPHATE URINE LEVEL; REVIEW; SECONDARY HYPERPARATHYROIDISM; COMPLICATION; IRON DEFICIENCY ANEMIA; METABOLISM; OSTEOMALACIA; PROSPECTIVE STUDY;

ANEMIA, IRON-DEFICIENCY; FIBROBLAST GROWTH FACTORS; HUMANS; HYPOPHOSPHATEMIA; IRON; OSTEOMALACIA; PROSPECTIVE STUDIES;

EID: 85115007696     PISSN: 87563282     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bone.2021.116202     Document Type: Review

References (45)

1. Pasricha, S.R., Tye-Din, J., Muckenthaler, M.U., Swinkels, D.W., Iron deficiency. Lancet 397 (2021), 233–248.
2. Camaschella, C., Iron-deficiency anemia. N. Engl. J. Med. 372 (2015), 1832–1843.
3. Jahn, M.R., et al. A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. Eur. J. Pharm. Biopharm. 78 (2011), 480–491.
4. Neiser, S., et al. Physico-chemical properties of the new generation IV iron preparations ferumoxytol, iron isomaltoside 1000 and ferric carboxymaltose. Biometals 28 (2015), 615–635.
5. Geisser, P., Baer, M., Schaub, E., Structure/histotoxicity relationship of parenteral iron preparations. Arzneimittelforschung 42 (1992), 1439–1452.
6. Onken, J.E., et al. A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Transfusion 54 (2014), 306–315.
7. Stein, J., et al. Safety and efficacy of intravenous iron isomaltoside for correction of anaemia in patients with inflammatory bowel disease in everyday clinical practice. Scand. J. Gastroenterol. 53 (2018), 1059–1065.
8. Adkinson, N.F., et al. Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: a randomized trial. Am. J. Hematol. 93 (2018), 683–690.
9. Wolf, M., et al. Effects of Iron isomaltoside vs ferric carboxymaltose on hypophosphatemia in iron-deficiency anemia: two randomized clinical trials. JAMA 323 (2020), 432–443.
10. Wolf, M., et al. Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight, 3, 2018.
11. Wolf, M., et al. Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight, 3, 2018, e124486.
12. Bellos, I., Frountzas, M., Pergialiotis, V., Comparative risk of hypophosphatemia following the administration of intravenous iron formulations: a network meta-analysis. Transfus. Med. Rev. 34 (2020), 188–194.
13. Glaspy, J.A., et al. Hypophosphatemia associated with intravenous iron therapies for iron deficiency anemia: a systematic literature review. Ther. Clin. Risk Manag. 16 (2020), 245–259.
14. Rosano, G., et al. A pooled analysis of serum phosphate measurements and potential hypophosphataemia events in 45 interventional trials with ferric carboxymaltose. J. Clin. Med., 9, 2020.
15. Schaefer, B., et al. Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside-a systematic review and meta-analysis. Br. J. Clin. Pharmacol. 87 (2021), 2256–2273.
16. Schaefer, B., et al. Choice of high-dose intravenous iron preparation determines hypophosphatemia risk. PLoS One, 11, 2016, e0167146.
17. Frazier, R., et al. Effects of ferric carboxymaltose on markers of mineral and bone metabolism: a single-center prospective observational study of women with iron deficiency. Bone, 141, 2020, 115559.
18. Detlie, T.E., et al. Incidence of hypophosphatemia in patients with inflammatory bowel disease treated with ferric carboxymaltose or iron isomaltoside. Aliment. Pharmacol. Ther. 50 (2019), 397–406.
19. Wolf, M., Koch, T.A., Bregman, D.B., Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J. Bone Miner. Res. 28 (2013), 1793–1803.
20. Emrich, I.E., et al. Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study. BMC Med., 18, 2020, 178.
21. Edmonston, D., Wolf, M., FGF23 at the crossroads of phosphate, iron economy and erythropoiesis. Nat. Rev. Nephrol. 16 (2020), 7–19.
22. Schaefer, B., et al. Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside-a systematic review and meta-analysis. Br. J. Clin. Pharmacol. 87:5 (2020), 2256–2273, 10.1111/bcp.14643.
23. Takashi, Y., et al. Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation. Proc. Natl. Acad. Sci. U. S. A. 116 (2019), 11418–11427.
24. David, V., et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int. 89 (2016), 135–146.
25. Yamamoto, H., et al. Posttranslational processing of FGF23 in osteocytes during the osteoblast to osteocyte transition. Bone 84 (2016), 120–130.
26. Topaz, O., et al. Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat. Genet. 36 (2004), 579–581.
27. Schaefer, B., Meindl, E., Wagner, S., Tilg, H., Zoller, H., Intravenous iron supplementation therapy. Mol. Asp. Med., 75, 2020, 100862.
28. Minisola, S., et al. Tumour-induced osteomalacia. Nat. Rev. Dis. Primers, 3, 2017, 17044.
29. Elder, C.J., Bishop, N.J., Rickets. Lancet 383 (2014), 1665–1676.
30. Zoller, H., Schaefer, B., Glodny, B., Iron-induced hypophosphatemia: an emerging complication. Curr. Opin. Nephrol. Hypertens. 26 (2017), 266–275.
31. Schaefer, B., Glodny, B., Wolf, M., Zoller, H., Letter: inconsistency in reporting of hypophosphatemia after intravenous iron. Aliment. Pharmacol. Ther. 46 (2017), 641–643.
32. Peach, H., Compston, J.E., Vedi, S., Horton, L.W., Value of plasma calcium, phosphate, and alkaline phosphatase measurements in the diagnosis of histological osteomalacia. J. Clin. Pathol. 35 (1982), 625–630.
33. Eastell, R., Garnero, P., Audebert, C., Cahall, D.L., Reference intervals of bone turnover markers in healthy premenopausal women: results from a cross-sectional European study. Bone 50 (2012), 1141–1147.
34. Walton, R.J., Bijvoet, O.L., Nomogram for derivation of renal threshold phosphate concentration. Lancet 2 (1975), 309–310.
35. Phan, C.M., Guglielmi, G., Metabolic bone disease in patients with malabsorption. Semin. Musculoskelet. Radiol. 20 (2016), 369–375.
36. McKenna, M.J., Heffernan, E., Hurson, C., McKiernan, F.E., Clinician approach to diagnosis of stress fractures including bisphosphonate-associated fractures. QJM 107 (2014), 99–105.
37. European Medicines Agency, Amendments to the product information of the nationally authorised medicinal product. https://www.ema.europa.eu/en/documents/psusa/iron-parenteral-preparations-except-iron-dextran-cmdh-scientific-conclusions-grounds-variation/00010236/202001_en.pdf.
38. American Regent Inc., Vifor (International) Inc, Switzerland. INJECTAFER® (ferric carboxymaltose injection), [package insert]., U.S. Food and Drug Administration website https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203565s013lbl.pdf, 2020 (Revised September). (Accessed 31 January 2021)
39. Amarnani, R., Travis, S., Javaid, M.K., Novel use of burosumab in refractory iron-induced FGF23-mediated hypophosphataemic osteomalacia. Rheumatology 59:8 (2020), 2166–2168, 10.1093/rheumatology/kez627 (Oxford).
40. Chen, Y.J., Lim, C., McCormick, J., Resistant iron-induced hypophosphatemia following colorectal surgery. N. Z. Med. J. 132 (2019), 72–75.
41. Urbina, T., et al. Iron supplementation-induced phosphaturic osteomalacia: FGF23 is the culprit. J. Bone Miner. Res. 33 (2018), 540–542.
42. Anand, G., Schmid, C., Severe hypophosphataemia after intravenous iron administration. BMJ Case Rep., 2017, 2017.
43. Bartko, J., et al. Hypophosphatemia, severe bone pain, gait disturbance, and fatigue fractures after iron substitution in inflammatory bowel disease: a case report. J. Bone Miner. Res. 33 (2018), 534–539.
44. Amarnani, R., Travis, S., Javaid, M.K., Novel use of burosumab in refractory iron-induced FGF23-mediated hypophosphataemic osteomalacia. Rheumatology (Oxford) 59 (2020), 2166–2168.
45. Geller, J.L., et al. Cinacalcet in the management of tumor-induced osteomalacia. J. Bone Miner. Res. 22 (2007), 931–937.