2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Severe osteomalacia with multiple insufficiency fractures secondary to intravenous iron therapy in a patient with Rendu-Osler-Weber syndrome

      case-report

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Summary

          This case report describes a 65-year-old man with a Rendu-Osler-Weber syndrome with secondary chronic anaemia, who received multiple intravenous (IV) iron infusions and sustained diffuse bone pain secondary to multiple insufficiency fractures. Laboratory study confirmed fibroblast growth factor 23 (FGF-23)-mediated hypophosphatemia as the main cause of a severe osteomalacia induced by ferric carboxymaltose (FCM).

          After 3 months or oral phosphate replacement and switching to iron sucrose, serum phosphate levels were normalized and patient improved clinically.

          Introduction

          Some drugs can induce asymptomatic hypophosphatemia, which if sustained, can lead to a severe osteomalacia with multiple skeletal fractures. This complication has also been described with IV iron therapy.

          Methods

          This case report describes a patient with Rendu-Osler-Weber syndrome with chronic iron deficiency anaemia, recurrently treated with FCM, who developed a severe osteomalacia with multiple skeletal fractures.

          Results

          Laboratory study showed hypophosphatemia, with high ALP and high FGF-23. Images studies confirmed bone mass loss and multiple insufficiency fractures. A Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) did not show hidden tumor, so a diagnosis of FCM-induced hypophosphatemic osteomalacia was performed. Phosphate replacement improved clinical symptoms of the patient.

          Conclusion

          Intravenous iron therapy, mainly FCM form, can cause hypophosphatemia, and in some cases induce a severe osteomalacia with multiple fractures, so it seems advisable to monitor serum phosphate levels in high risk patients, as those who receive repeated dose.

          Highlights

          • Intravenous iron therapy can cause hypophosphatemia and in some cases osteomalacia.

          • Ferric carboxymaltose can raise fibroblast growth factor 23, a phosphaturic hormone.

          • Osteomalacia should be considered if a patient treated with iron therapy develops pain.

          • It's advisable to monitor serum phosphate in patients who receive iron therapy.

          • In case of persistent hypophosphatemia, switch to another iron therapy is suggested.

          Related collections

          Most cited references17

          • Record: found
          • Abstract: found
          • Article: not found

          Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women.

          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 <2.0 mg/dL in 10 women in the FCM group compared to none in the iron dextran group. Reduced serum phosphate was accompanied by increased urinary fractional excretion of phosphate, decreased calcitriol levels, and increased parathyroid hormone levels. These findings suggest that iron deficiency increases cFGF23 levels, and that certain iron preparations temporarily increase iFGF23 levels. We propose that intravenous iron lowers cFGF23 in humans by reducing 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. Copyright © 2013 American Society for Bone and Mineral Research.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Hypophosphatemia: an update on its etiology and treatment.

              Phosphate plays a key role in several biological processes. In recent years, new insights have been obtained into the regulation of the phosphate metabolism, including a growing amount of evidence suggesting that factors other than parathyroid hormone (PTH) and vitamin D are involved in maintaining the phosphate balance. A new class of phosphate-regulating factors, the so-called "phosphatonins," have been shown to be important in phosphate-wasting diseases. However, the role of the phosphatonins in the normal human homeostasis remains to be established. The incidence of hypophosphatemia in selected patient series can be more than 20%, with clinical sequelae ranging from mild to life threatening. Only when combined with phosphate depletion does hypophosphatemia become clinically significant. The factors that are involved in the phosphate homeostasis, the pathophysiology, the relevance in patient care, the clinical manifestations, and an appropriate management of phosphate depletion are discussed in this review.
                Bookmark

                Author and article information

                Contributors
                Journal
                Bone Rep
                Bone Rep
                Bone Reports
                Elsevier
                2352-1872
                22 August 2020
                December 2020
                22 August 2020
                : 13
                : 100712
                Affiliations
                [a ]Department of Internal Medicine, University Hospital Parc Taulí, Universitat Autònoma de Barcelona (UAB), Sabadell, Barcelona, Spain
                [b ]Department of Rheumatology, University Hospital Parc Taulí, Universitat Autònoma de Barcelona (UAB), Sabadell, Barcelona, Spain
                [c ]Department of Hematology, University Hospital Parc Taulí, Universitat Autònoma de Barcelona (UAB), Sabadell, Barcelona, Spain
                [d ]Department of Nuclear Medicine, University Hospital Parc Taulí, Universitat Autònoma de Barcelona (UAB), Sabadell, Barcelona, Spain
                Author notes
                [* ]Corresponding author at: Department of Internal Medicine, Hospital Universitari Parc Taulí, Parc Taulí 1, 08208 Sabadell, Barcelona, Spain. elcallejas@ 123456tauli.cat
                Article
                S2352-1872(20)30472-1 100712
                10.1016/j.bonr.2020.100712
                7475229
                06ee6545-1723-4068-b297-88d180b75e4f
                © 2020 Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 22 June 2020
                : 8 August 2020
                : 19 August 2020
                Categories
                Article

                osteomalacia,fibroblast growth factor 23,hypophosphatemia,intravenous iron therapy

                Comments

                Comment on this article