{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:56:42Z","timestamp":1789394202509,"version":"build-2803163510"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"Supplement_5","license":[{"start":{"date-parts":[[2025,1,5]],"date-time":"2025-01-05T00:00:00Z","timestamp":1736035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intravenous iron infusions (particularly ferric carboxymaltose) are associated with hypophosphatemia. This is mediated by increased fibroblast growth factor 23 (FGF-23), resulting in decreased activation of 25(OH)vitamin D to 1,25(OH)2 vitamin D and increased urinary phosphate excretion. Similarly, parenteral antiresorptive agents can lead to hypocalcemia due to reduced bone calcium mobilization, increasing parathyroid hormone (PTH) secretion, and exacerbating kidney phosphate excretion. When given concurrently, electrolyte disturbances can be severe and refractory to treatment, necessitating intravenous replacement, frequent monitoring, and prolonged hospitalization. We describe a case series of six patients with severe hypophosphatemia and hypocalcemia from concurrent administration of intravenous iron and antiresorptive therapy. The average time to hypophosphatemia following iron therapy in the presence of antiresorptives was 17.5\u00a0days. This is consistent with the nadir of phosphate 2\u00a0weeks following iron infusion and appears to be prolonged and exacerbated by antiresorptive therapy, increasing urinary phosphate loss through increased PTH activity. With the increasing popularity of intravenous iron infusions and parenteral antiresorptive agents, the interplay of these medications is an important consideration for clinicians. The emerging administration of these agents in the community and fragmentation of care across primary and specialist networks create the risk of unintentional concurrent use. Increased awareness of their impact on calcium-phosphate homeostasis is needed to mitigate the risk of severe electrolyte derangements with consideration of alternate iron formulations preferentially in those receiving medications for osteoporosis.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae177","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T07:18:29Z","timestamp":1735802309000},"page":"v88-v93","source":"Crossref","is-referenced-by-count":7,"title":["\u201cDouble trouble\u201d: the impact of iron infusion and antiresorptive therapy on calcium-phosphate homeostasis"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3237-9492","authenticated-orcid":false,"given":"Gabrielle","family":"Stokes","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrinology, Westmead Hospital , Westmead, NSW, 2145 ,","place":["Australia"]},{"name":"Bone and Muscle Research Group, Faculty of Medicine, Nursing and Health Sciences, Monash University , VIC, 3168 ,","place":["Australia"]},{"name":"Metabolic Bone Research Group, Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research , Clayton, VIC, 3168 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Sheu","sequence":"additional","affiliation":[{"name":"Bone Epidemiology, Clinical and Translation Science Lab, Skeletal Diseases Program, Garvan Institute of Medical Research , Darlinghurst, NSW, 2010 ,","place":["Australia"]},{"name":"School of Clinical Medicine, University of New South Wales , Sydney, NSW, 2052 ,","place":["Australia"]},{"name":"Department of Endocrinology, St Vincent\u2019s Hospital , Darlinghurst, NSW, 2010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8746-5529","authenticated-orcid":false,"given":"Christian M","family":"Girgis","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Westmead Hospital , Westmead, NSW, 2145 ,","place":["Australia"]},{"name":"Faculty of Medicine and Health, University of Sydney , Sydney, NSW, 2006 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P","family":"White","sequence":"additional","affiliation":[{"name":"Bone Epidemiology, Clinical and Translation Science Lab, Skeletal Diseases Program, Garvan Institute of Medical Research , Darlinghurst, NSW, 2010 ,","place":["Australia"]},{"name":"Department of Endocrinology and Metabolism, Prince of Wales Hospital , Randwick, NSW, 2031 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"2025122308364334600_ref1","doi-asserted-by":"publisher","first-page":"116202","DOI":"10.1016\/j.bone.2021.116202","article-title":"Hypophosphatemia after intravenous iron therapy: comprehensive review of clinical findings and recommendations for management","volume":"154","author":"Schaefer","year":"2022","journal-title":"Bone"},{"issue":"7","key":"2025122308364334600_ref2","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1210\/jc.2008-2396","article-title":"FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study","volume":"94","author":"Schouten","year":"2009","journal-title":"JCEM"},{"issue":"2","key":"2025122308364334600_ref3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.5694\/mja2.50618","article-title":"Rapid increase in intravenous iron therapy for women of reproductive age in Australia","volume":"213","author":"Shand","year":"2020","journal-title":"Med J Aust"},{"issue":"8","key":"2025122308364334600_ref4","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1002\/jbmr.1923","article-title":"Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women","volume":"28","author":"Wolf","year":"2013","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2025122308364334600_ref5","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s40610-019-0110-9","article-title":"Regulation of fibroblast growth factor 23 by iron, EPO, and HIF","volume":"5","author":"Wheeler","year":"2019","journal-title":"Curr Mol Biol Rep"},{"key":"2025122308364334600_ref6","doi-asserted-by":"publisher","first-page":"100862","DOI":"10.1016\/j.mam.2020.100862","article-title":"Intravenous iron supplementation therapy","volume":"75","author":"Schaefer","year":"2020","journal-title":"Mol Asp Med"},{"issue":"1","key":"2025122308364334600_ref7","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s11657-022-01139-0","article-title":"Trends in osteoporosis diagnosis and management in Australia","volume":"17","author":"Smith","year":"2022","journal-title":"Arch Osteoporos"},{"issue":"4","key":"2025122308364334600_ref8","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1111\/ajco.12517","article-title":"Denosumab: prevention and management of hypocalcemia, osteonecrosis of the jaw and atypical fractures","volume":"13","author":"Pittman","year":"2017","journal-title":"Asia Pac J Clin Oncol"},{"issue":"13","key":"2025122308364334600_ref9","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1016\/j.ejca.2015.05.016","article-title":"Hypocalcaemia in patients with metastatic bone disease treated with denosumab","volume":"51","author":"Body","year":"2015","journal-title":"Eur J Cancer"},{"issue":"9","key":"2025122308364334600_ref10","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1111\/nep.14078","article-title":"Severe hypocalcaemia following denosumab and iron infusion","volume":"27","author":"Cohen","year":"2022","journal-title":"Nephrology (Carlton)"},{"issue":"11","key":"2025122308364334600_ref11","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1111\/imj.16261","article-title":"Severe hypocalcaemia after denosumab and intravenous iron: a cautionary tale","volume":"53","author":"Cuthbertson","year":"2023","journal-title":"Intern Med J"},{"issue":"5","key":"2025122308364334600_ref12","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1002\/jgh3.12150","article-title":"Symptomatic severe hypophosphataemia after intravenous ferric carboxymaltose","volume":"3","author":"Fang","year":"2019","journal-title":"JGH Open"},{"issue":"7","key":"2025122308364334600_ref13","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1111\/imj.16156","article-title":"Interaction between ferric carboxymaltose and denosumab causing severe hypocalcaemia and hypophosphataemia in a patient without chronic kidney disease","volume":"53","author":"Muhandiramge","year":"2023","journal-title":"Intern Med J"},{"issue":"3","key":"2025122308364334600_ref14","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/imj.13001","article-title":"Severe hypocalcaemia and hypophosphataemia following intravenous iron and denosumab: a novel drug interaction","volume":"46","author":"Smith","year":"2016","journal-title":"Intern Med J"},{"issue":"1","key":"2025122308364334600_ref15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/jppr.1791","article-title":"Hypocalcaemia and hypophosphataemia following denosumab and IV ferric carboxymaltose in an older patient with normal renal function","volume":"52","author":"Tai","year":"2022","journal-title":"J Pharm Pract Res"},{"issue":"2","key":"2025122308364334600_ref16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1210\/jcemcr\/luae005","article-title":"Concurrent Denosumab and parenteral iron therapy precipitating severe hypocalcaemia and hypophosphataemia","volume":"2","author":"Ye","year":"2024","journal-title":"JCEM Case Reports"},{"issue":"1","key":"2025122308364334600_ref17","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s00198-023-06926-0","article-title":"Prevalence of denosumab-induced hypocalcemia: a retrospective observational study of patients routinely monitored with ionized calcium post-injection","volume":"35","author":"Sp\u00e5ngeus","year":"2024","journal-title":"Osteoporos Int"},{"issue":"4","key":"2025122308364334600_ref18","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1210\/clinem\/dgab852","article-title":"Risk factors for and effects of persistent and severe hypophosphatemia following ferric carboxymaltose","volume":"107","author":"Schaefer","year":"2022","journal-title":"JCEM"},{"issue":"5","key":"2025122308364334600_ref19","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1111\/bcp.14643","article-title":"Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside\u2014a systematic review and meta-analysis","volume":"87","author":"Schaefer","year":"2021","journal-title":"Br J Clin Pharmacol"},{"key":"2025122308364334600_ref20","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.2147\/dddt.S55499","article-title":"Optimizing iron delivery in the management of anemia: patient considerations and the role of ferric carboxymaltose","volume":"8","author":"Toblli","year":"2014","journal-title":"Drug Des Devel Ther"},{"key":"2025122308364334600_ref21","article-title":"Amendments to the product information of the nationally authorised medicinal product","year":"2020"},{"key":"2025122308364334600_ref22"},{"key":"2025122308364334600_ref23"},{"issue":"4","key":"2025122308364334600_ref24","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1136\/gutjnl-2022-327897","article-title":"Hypophosphataemia following ferric derisomaltose and ferric carboxymaltose in patients with iron deficiency anaemia due to inflammatory bowel disease (PHOSPHARE-IBD): a randomised clinical trial","volume":"72","author":"Zoller","year":"2023","journal-title":"Gut"},{"issue":"12","key":"2025122308364334600_ref25","doi-asserted-by":"publisher","first-page":"e0167146","DOI":"10.1371\/journal.pone.0167146","article-title":"Choice of high-dose intravenous iron preparation determines hypophosphatemia risk","volume":"11","author":"Schaefer","year":"2016","journal-title":"PLoS One"},{"key":"2025122308364334600_ref26","doi-asserted-by":"publisher","first-page":"245","DOI":"10.2147\/tcrm.S243462","article-title":"Hypophosphatemia associated with intravenous iron therapies for iron deficiency anemia: a systematic literature review","volume":"16","author":"Glaspy","year":"2020","journal-title":"Ther Clin Risk Manag"},{"issue":"1","key":"2025122308364334600_ref27","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.ijgo.2015.09.007","article-title":"Randomized controlled trial comparing ferric carboxymaltose and iron sucrose for treatment of iron deficiency anemia due to abnormal uterine bleeding","volume":"133","author":"Mahey","year":"2016","journal-title":"Int J Gynaecol Obstet"},{"issue":"1","key":"2025122308364334600_ref28","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12884-019-2200-3","article-title":"Comparison of ferric Carboxymaltose and iron sucrose complex for treatment of iron deficiency anemia in pregnancy- randomised controlled trial","volume":"19","author":"Jose","year":"2019","journal-title":"BMC Pregnancy Childbirth"},{"issue":"4","key":"2025122308364334600_ref29","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1093\/ndt\/gft251","article-title":"Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial","volume":"29","author":"Onken","year":"2013","journal-title":"Nephrol Dial Transplant"},{"issue":"5","key":"2025122308364334600_ref30","doi-asserted-by":"publisher","first-page":"656","DOI":"10.7326\/m21-4009","article-title":"Risks for anaphylaxis with intravenous iron formulations: a retrospective cohort study","volume":"175","author":"Dave","year":"2022","journal-title":"Ann Intern Med"},{"issue":"23","key":"2025122308364334600_ref31","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124486","article-title":"Randomized trial of intravenous iron-induced hypophosphatemia","volume":"3","author":"Wolf","year":"2018","journal-title":"JCI Insight"},{"key":"2025122308364334600_ref32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2024\/8910092","article-title":"Hypocalcemia and hypophosphatemia following concurrent denosumab injection and ferric carboxymaltose infusion in a patient with normal renal function","volume":"2024","author":"Szwarcbard","year":"2024","journal-title":"Case Rep Endocrinol"},{"key":"2025122308364334600_ref33","doi-asserted-by":"publisher","first-page":"101759","DOI":"10.1016\/j.bonr.2024.101759","article-title":"Intravenous iron-induced hypophosphatemia and kidney stone disease","volume":"21","author":"Panzer","year":"2024","journal-title":"Bone Reports"},{"issue":"11","key":"2025122308364334600_ref34","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.1002\/jbmr.4705","article-title":"Multiple vertebral fractures after Denosumab discontinuation: FREEDOM and FREEDOM extension trials additional post hoc analyses","volume":"37","author":"Cosman","year":"2022","journal-title":"J Bone Miner Res"},{"issue":"8","key":"2025122308364334600_ref35","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1093\/rheumatology\/kez627","article-title":"Novel use of burosumab in refractory iron-induced FGF23-mediated hypophosphataemic osteomalacia","volume":"59","author":"Amarnani","year":"2020","journal-title":"Rheumatology (Oxford)"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jbmrplus\/advance-article-pdf\/doi\/10.1093\/jbmrpl\/ziae177\/61331125\/ziae177.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/9\/Supplement_5\/v88\/61331125\/ziae177.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/9\/Supplement_5\/v88\/61331125\/ziae177.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T13:36:49Z","timestamp":1766497009000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/9\/Supplement_5\/v88\/7942819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":35,"journal-issue":{"issue":"Supplement_5","published-print":{"date-parts":[[2025,12,23]]}},"URL":"https:\/\/doi.org\/10.1093\/jbmrpl\/ziae177","relation":{},"ISSN":["2473-4039"],"issn-type":[{"value":"2473-4039","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,12]]}}}