Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women
- 16 March 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 28 (8), 1793-1803
- https://doi.org/10.1002/jbmr.1923
Abstract
Fibroblast growth factor 23 (FGF23) is an osteocyte‐derived hormone that regulates phosphate and vitamin D homeostasis. Through unknown mechanisms, certain intravenous iron preparations induce acute, reversible increases in circulating FGF23 levels that lower serum phosphate in association with inappropriately low levels of calcitriol, similar to genetic diseases of primary FGF23 excess. In contrast, studies in wild‐type mice suggest that iron deficiency stimulates fgf23 transcription but does not result in hypophosphatemia because FGF23 is cleaved within osteocytes by an unknown catabolic system. We tested the association of iron deficiency anemia with C‐terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 55 women with a history of heavy uterine bleeding, and assessed the longitudinal biochemical response over 35 days to equivalent doses of randomly‐assigned, intravenous elemental iron in the form of ferric carboxymaltose (FCM) or iron dextran. Iron deficiency was associated with markedly elevated cFGF23 (807.8 ± 123.9 relative units [RU]/mL) but normal iFGF23 (28.5 ± 1.1 pg/mL) levels at baseline. Within 24 hours of iron administration, cFGF23 levels fell by approximately 80% in both groups. In contrast, iFGF23 transiently increased in the FCM group alone, and was followed by a transient, asymptomatic reduction in serum phosphate fgf23 transcription as it does in mice, whereas carbohydrate moieties in certain iron preparations may simultaneously inhibit FGF23 degradation in osteocytes leading to transient increases in iFGF23 and reduced serum phosphate.Keywords
This publication has 23 references indexed in Scilit:
- Safety and Efficacy of Intravenous Ferric Carboxymaltose (750 mg) in the Treatment of Iron Deficiency Anemia: Two Randomized, Controlled TrialsAnemia, 2012
- Iron Modifies Plasma FGF23 Differently in Autosomal Dominant Hypophosphatemic Rickets and Healthy HumansJournal of Clinical Endocrinology & Metabolism, 2011
- Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in miceProceedings of the National Academy of Sciences of the United States of America, 2011
- A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patientsNephrology Dialysis Transplantation, 2010
- FGF-23: More than a regulator of renal phosphate handling?Journal of Bone and Mineral Research, 2010
- FGF23 Elevation and Hypophosphatemia after Intravenous Iron Polymaltose: A Prospective StudyJournal of Clinical Endocrinology & Metabolism, 2009
- Iron polymaltose-induced FGF23 elevation complicated by hypophosphataemic osteomalaciaAnnals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2009
- Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anemia: a randomized controlled clinical trialAmerican Journal of Obstetrics and Gynecology, 2008
- Fibroblast Growth Factor 23 and Mortality among Patients Undergoing HemodialysisThe New England Journal of Medicine, 2008
- Saccharated Ferric Oxide-Induced Osteomalacia in Japan: Iron-Induced Osteopathy Due to Nephropathy.Endocrine Journal, 1998