Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.2039
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
High-dose intravenous iron is an effective 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.
To investigate mechanisms behind the development of hypophosphatemia after intravenous iron treatment, and disclose symptoms and clinical manifestations related to hypophosphatemia short-term.
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 received one dose of 1000 mg of either FCM or ferric derisomaltose (FDI) and were followed for an observation period of at least 7 wk. Blood and urine samples were collected for relevant analyses at baseline, week 2 and at week 6. Clinical symptoms were assessed at the same timepoints using a respiratory function test, a visual analogue scale, and a health-related quality of life questionnaire.
A total of 106 patients was available for analysis in this study. The FCM treatment group consisted of 52 patients and hypophosphatemia was present in 72.5% of the patients at week 2, and in 21.6% at week 6. In comparison, the FDI treatment group consisted of 54 patients and 11.3% of the patients had hypophosphatemia at week 2, and 3.7% at week 6. The difference in incidence was highly significant at both week 2 and 6 (P < 0.001 and P < 0.013, respectively). We observed a significantly higher mean concentration of intact fibroblast growth factor 23 (P < 0.001), a significant rise in mean urine fractional excretion of phosphate (P = 0.004), a significant decrease of 1,25-dihydroxyvitamin D (P < 0.001) and of ionised calcium levels (P < 0.012) in the FCM-treated patients compared with patients who received FDI. No clinical symptoms could with certainty be related to hypophosphatemia, since neither the respiratory function test, SF-36 (36-item short form health survey) or the visual analogue scale scores resulted in significant differences between patients who developed hypophosphatemia or not.
Fibroblast growth factor 23 has a key role in FCM induced hypophosphatemia, probably by inducing loss of phosphate in the urine. Short-term clinical impact of hypophosphatemia was not demonstrated.
Core Tip: High-dose intravenous iron is an effective treatment for iron deficiency anaemia (IDA) in inflammatory bowel disease (IBD). However, ferric carboxymaltose (FCM) is associated with development of hypophosphatemia. This study of adult IBD patients with IDA investigated the mechanisms and clinical manifestations related to hypophosphatemia after treatment of either FCM or ferric derisomaltose (FDI). The incidence of hypophosphatemia was significantly higher after FCM than FDI, and fibroblast growth factor 23 had a key role, inducing loss of phosphate in the urine along with a significant lowering of 1,25-dihydroxyvitamin D and ionised calcium levels. Short-term clinical impact was not demonstrated.