Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2021; 27(17): 2039-2053
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.2039
Hypophosphatemia after high-dose intravenous iron treatment in patients with inflammatory bowel disease: Mechanisms and possible clinical impact
Trond Espen Detlie, Jonas Christoffer Lindstrøm, Marte Eide Jahnsen, Elisabeth Finnes, Heinz Zoller, Bjørn Moum, Jørgen Jahnsen
Trond Espen Detlie, Marte Eide Jahnsen, Jørgen Jahnsen, Department of Gastroenterology, Akershus University Hospital, Lørenskog 1478, Norway
Trond Espen Detlie, Jonas Christoffer Lindstrøm, Bjørn Moum, Jørgen Jahnsen, Institute of Clinical Medicine, University of Oslo, Oslo 0316, Norway
Jonas Christoffer Lindstrøm, Health Services Research Unit, Akershus University Hospital, Lørenskog 1478, Norway
Elisabeth Finnes, Bjørn Moum, Division of Medicine, Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo 0424, Norway
Heinz Zoller, Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck A-6020, Austria
Author contributions: Detlie TE, Moum B and Jahnsen J contributed responsible for the concept and design of the study, acquisition of data, analysis and interpretation of data, and drafting the article and revising it critically for important intellectual content; Lindstrøm JC and Zoller H performed analysis and interpretation of data, and contributed critical revision of the manuscript for important intellectual content; Jahnsen ME and Finnes E contributed acquisition of data and critical revision of the manuscript for important intellectual content; Moum B and Jahnsen J contributed equally as senior authors; all the authors read and approved the final version of the manuscript.
Institutional review board statement: The study was reviewed and approved by the Regionale Komiteer for Medisinsk og Helsefaglig Forskningsetikk (REK) in Helse Sør-Øst, Norway/Regional Ethics Committee from the South-East Health Region of Norway.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Detlie TE has served as a speaker, consultant or advisory board member for AbbVie, Ferring, Pfizer, Pharmacosmos, Tillotts, and Vifor Pharma. He has received unrestricted research grants from AbbVie, and Pharmacosmos. Jahnsen ME has received lecture fees from Pharmacosmos. Zoller H has served as a speaker, consultant or advisory board member for AbbVie, BMS, Gilead, MSD, Merck, Merz, Novartis, Pharmacosmos, and Vifor Pharma. Moum B has served as a speaker, consultant or advisory board member for AbbVie, Ferring, Janssen, Roche, and Takeda. Jahnsen J has served as a speaker, consultant or advisory board member for AbbVie, Astro Pharma, Boehringer Ingelheim, BMS, Celltrion, Ferring, Hikma, Janssen, Meda, MSD, Napp Pharma, Novartis, Orion Pharma, Pfizer, Pharmacosmos, Roche, Takeda, Tillotts, and Sandoz. The other authors have no disclosures.
Data sharing statement: The data underlying this article were provided by Akershus University Hospital and Oslo University Hospital Ullevål by permission. Data will be shared on request to the corresponding author with permission of Akershus University Hospital and Oslo University Hospital Ullevål.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Trond Espen Detlie, MD, Academic Fellow, Academic Research, Consultant Physician-Scientist, Doctor, Department of Gastroenterology, Akershus University Hospital, Sykehusveien 25, Lørenskog 1478, Norway. t.e.detlie@medisin.uio.no
Received: January 28, 2021
Peer-review started: January 28, 2021
First decision: March 6, 2021
Revised: March 19, 2021
Accepted: April 21, 2021
Article in press: April 21, 2021
Published online: May 7, 2021
ARTICLE HIGHLIGHTS
Research background

High-dose intravenous iron is an effective and frequently used treatment option for iron deficiency (ID) or ID anaemia (IDA) in inflammatory bowel disease (IBD). However, treatment with ferric carboxymaltose (FCM) has been associated with the development of hypophosphatemia.

Research motivation

We aimed to investigate the occurrence of hypophosphatemia after treatment with either FCM and ferric derisomaltose (FDI) for ID or IDA in patients with IBD.

Research objectives

In this part of the study, we aimed to disclose underlying mechanism behind the development of hypophosphatemia after treatment with high dose intravenous iron and whether hypophosphatemia had a clinical impact on these patients.

Research methods

A prospective observational study of adult IBD patients with ID or IDA was conducted between February 1, 2017 and July 1, 2018 at two separate university hospitals in the southeast region of Norway. Patients were recruited consecutively and received one dose of 1000 mg of either FCM or FDI, and were followed for an observation period of at least 7 wk at three timepoints; baseline, week 2 and week 6. Blood and urine samples were collected for relevant analyses at all three visits in addition to assessment of clinical symptoms using a respiratory function test, a visual analogue scale, and a health-related quality of life questionnaire.

Research results

Our study results demonstrate an association between FCM treatment and the development of hypophosphatemia by increasing the level of intact Fibroblast Growth Factor 23 (iFGF23) and phosphate wasting in the urine. Moreover, we observed a significant decline in active Vitamin D and ionised calcium. No clinical impact was detected by applying Short Form-36 questionnaire, visual analogue scale score and real-time position management breathing test in an observation period of 6 wk.

Research conclusions

FCM treatment is associated with the development of hypophosphatemia in patients with IBD. This is due to increased formation of iFGF23 which in turn probably results in an increase of urinary phosphate output. No clinical impact was detected nor excluded. Assumably our study is underpowered together with a too short observation period to provide solid information with regard to clinical impact of hypophosphatemia.

Research perspectives

Based on our results we encourage clinicians to be aware of the risk of developing hypophosphatemia after treatment with FCM. Larger studies with a longer observation period to detect possible clinical impact of hypophosphatemia is desirable.