Abstract
Background: Two weekly infusions of ferric carboxymaltose (FCM) are commonly prescribed for treatment of iron-deficiency anemia. However, administration of FCM increases intact levels of fibroblast growth factor 23 (FGF23), which causes hypophosphatemia due to renal phosphate wasting, calcitriol deficiency and secondary hyperparathyroidism. The adverse effects of FCM on mineral metabolism and bone health emerged from case reports and secondary analyses of trials. Data on these safety signals with FCM in clinical practice are limited because markers of mineral and bone metabolism are not routinely checked. Methods: To obtain real-world experience with effects of FCM on mineral and bone metabolism, we conducted a prospective observational study of 16 women who were managed at a single-center hematology clinic for iron-deficiency anemia. From October 2016 to February 2018, all participants received two weekly infusions of FCM at a hematology infusion clinic. We hypothesized that FCM would decrease phosphate, increase intact FGF23 (iFGF23), and decrease c-terminal FGF23 (cFGF23). Secondary outcomes were changes in hemoglobin, iron indices, urine fractional excretion of phosphate (FePi), parathyroid hormone (PTH), calcitriol, calcium, osteocalcin, and bone-specific alkaline phosphatase (BAP). FCM was administered at weeks zero and one, and we measured laboratory values at weeks zero, one, two, and five of the study. We used linear mixed models to analyze the significance of the changes in laboratory values over time. Results: After two FCM infusions, nearly all (14 of 16) participants developed hypophosphatemia. iFGF23 increased, cFGF23 decreased, and phosphate decreased significantly from week zero to week two (iFGF23 increased by +134.0% [40.6, 305.8], p < 0.001; cFGF23 decreased by −516.3% [−1332.7, −142.7], p = 0.002; phosphate decreased by −49.8 ± 15.4%, p < 0.001). There was also a significant increase in FePi, PTH, and BAP and a significant decrease in calcitriol and calcium from week zero to week two. There was no significant change in osteocalcin during this time period. iFGF23, but not PTH, was independently associated with decreased phosphate. iFGF23 was also significantly associated with decrease in calcitriol from week zero to week two. Elevation in BAP suggests disordered bone mineralization in response to FCM therapy. Conclusion: In this prospective observational study of women with iron deficiency anemia, two FCM infusions significantly altered markers of bone mineralization and mineral metabolism. The results suggest that FCM should be used cautiously in the treatment of iron-deficiency anemia.
| Original language | English (US) |
|---|---|
| Article number | 115559 |
| Journal | Bone |
| Volume | 141 |
| DOIs | |
| State | Published - Dec 2020 |
Funding
This study was supported by grants P30DK114857, R01DK102438 (TI), T32DK108738 (RF), and a National Kidney Foundation of Illinois Young Investigator Grant (RM). Research reported in this publication was also supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number KL2TR001424 and by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. RM has interest in Abbot Laboratories, AbbVie, Inc. and Teva Pharmaceuticals Industries Ltd. and has received honoraria from Akebia/Otsuka. TI has received consultant honoraria from Kyowa Kirin and LifeSci Capital. MW has received research support, honoraria or consultant fees from Akebia, Amag, Amgen, Ardelyx, DiaSorin, Keryx, and Shire. VD receives research funding from Keryx Biopharmaceuticals and has received research funding from Vifor Pharma and consulting honoraria from Keryx Biopharmaceuticals, Vifor Pharma, Luitpold, and Amgen. BS has had consulting meetings with Celgene, Apex Oncology, and Kartos. The remaining authors declare that they have no relevant financial interests. This study was supported by grants P30DK114857, R01DK102438 (TI), T32DK108738 (RF), and a National Kidney Foundation of Illinois Young Investigator Grant (RM). Research reported in this publication was also supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences , Grant Number KL2TR001424 and by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number UL1TR001422 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. RM has interest in Abbot Laboratories, AbbVie, Inc. and Teva Pharmaceuticals Industries Ltd., and has received honoraria from Akebia/Otsuka. TI has received consultant honoraria from Kyowa Kirin and LifeSci Capital. MW has received research support, honoraria or consultant fees from Akebia, Amag, Amgen, Ardelyx, DiaSorin, Keryx, and Shire. VD receives research funding from Keryx Biopharmaceuticals and has received research funding from Vifor Pharma and consulting honoraria from Keryx Biopharmaceuticals, Vifor Pharma, Luitpold, and Amgen. BS has had consulting meetings with Celgene, Apex Oncology, and Kartos. The remaining authors declare that they have no relevant financial interests.
Keywords
- Bone-specific alkaline phosphatase
- Ferric carboxymaltose
- Fibroblast growth factor 23
- Hypophosphatemia
- Iron-deficiency anemia
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology
- Histology