ferric-carboxymaltose and Osteomalacia

Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.

Topics: Anemia, Hypochromic; Calcitriol; Ferric Compounds; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Homeostasis; Humans; Hypophosphatemia; Infusions, Parenteral; Iron; Iron Deficiencies; Kidney; Malabsorption Syndromes; Maltose; Osteomalacia; Parathyroid Hormone; Phosphorus; Phosphorus, Dietary

Osteomalacia is an uncommon, overlooked and debilitating metabolic bone disease with numerous aetiologies. Herein, we report an atypical cause of osteomalacia - intravenous iron therapy.. Description of a case report of hypophophatemic osteomalacia induced by ferric carboxymaltose infusions.. A 70-year-old male with Rendu-Osler-Weber syndrome requiring repeated infusions of ferric carboxymaltose was admitted for disabling lower limb pain associated with persistent hypophosphatemia (1.6mg/dL) and increased urinary fractional excretion of phosphate (43%, UP04=118.3mg/dL), serum fibroblast growth factor 23 (324UA/mL), intact parathyroid hormone (110pg/mL) and bone alkaline phosphatase (40.1mcg/L). X-ray and CT of the feet showed severe diffuse bone demineralization. Feet MRI displayed a subchondral fracture of the cuneiform-navicular joints. Spine X-ray revealed dorsolumbar vertebral flattening. Somatostatin receptor PET scan excluded an occult tumor. Bone biopsy with histomorphometry confirmed the presence of osteomalacia. After excluding other causes, a diagnosis of hypophosphatemic osteomalacia induced by frequent ferric carboxymaltose infusions was made. The iron formulation was replaced by saccharated ferric oxide infusions and progressive titration of calcitriol up to 1.5mg/day and oral disodium phosphate up to 5740mg/day was started. After 6 months, there was a clear clinical and analytical improvement.. Osteomalacia may be a consequence of prolonged hypophosphatemia induced by recurrent ferric infusions, which is an uncommon and neglected bone adverse event of this therapy. Phosphate levels and bone symptoms should be monitored during repetitive iron infusions, maintaining a high level of suspicion for osteomalacia as it is important to identify and treat it in a timely manner, minimizing its severe morbidity.

Topics: Aged; Humans; Hypophosphatemia; Iron; Male; Osteomalacia; Phosphates

Hypophosphatemia, osteomalacia, and fractures are complications of certain intravenous iron formulations.. This study investigated risk factors for incident, severe, and persistent hypophosphatemia, and associated alterations in bone and mineral biomarkers following intravenous iron treatment.. We analyzed data from the PHOSPHARE-IDA randomized clinical trials, comprising 245 patients aged 18 years or older with iron deficiency anemia at 30 outpatient clinics in the United States who received intravenous ferric carboxymaltose (FCM) or ferric derisomaltose (FDI). Outcome measures included serum phosphate, intact fibroblast growth factor-23 (iFGF23), 1,25-dihydroxyvitamin D (1,25(OH)2D), ionized calcium, parathyroid hormone (PTH), and alkaline phosphatase.. FCM was the only consistent risk factor for incident hypophosphatemia (< 2.0 mg/dL; odds ratio vs FDI: 38.37; 95% CI: 16.62, 88.56; P < 0.001). Only FCM-treated patients developed severe hypophosphatemia (< 1.0 mg/dL; 11.3%; 13/115) or persistent hypophosphatemia (< 2.0 mg/dL at study end; 40.0%; 46/115). More severe hypophosphatemia associated with significantly greater increases in iFGF23, PTH, and alkaline phosphatase, and more severe decreases in 1,25(OH)2D and ionized calcium (all P < 0.05). Patients with persistent vs resolved hypophosphatemia demonstrated significantly greater changes in iFGF23, PTH, 1,25(OH)2D, and N-terminal procollagen-1 peptide levels (all P < 0.01), but alkaline phosphatase increased similarly in both groups.. Treatment with FCM was the only consistent risk factor for hypophosphatemia. Patients who developed severe or persistent hypophosphatemia after FCM treatment manifested more severe derangements in bone and mineral metabolism. Changes in bone biomarkers continued beyond resolution of hypophosphatemia, suggesting ongoing effects on bone that may help explain the association of FCM with osteomalacia and fractures.

Topics: Alkaline Phosphatase; Anemia, Iron-Deficiency; Biomarkers; Calcium; Disaccharides; Familial Hypophosphatemic Rickets; Female; Ferric Compounds; Humans; Hypophosphatemia; Iron; Male; Maltose; Minerals; Osteomalacia; Parathyroid Hormone; Risk Factors

Carboxymaltose iron (Ferinject®) is a formulation for intravenous (iv) administration, used for the treatment of iron deficiency anemia and/or iron deficiency when oral administration of iron is not effective or due to intolerance. Its safety profile is excellent with few, but not nonexistent, side effects. Hypophosphatemia has been described as one of them. It is usually mild, transient and asymptomatic. However, in some cases it may be accompanied by nausea, asthenia, in addition to muscular and neurological symptoms and hematological alterations. It is, therefore, a potentially serious adverse effect whose prevalence is unknown and which requires high clinical suspicion to be detected.

Topics: Ferric Compounds; Humans; Hypophosphatemia; Iron; Maltose; Osteomalacia

Topics: Adult; Anemia, Iron-Deficiency; Antibodies, Monoclonal, Humanized; Ferric Compounds; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypophosphatemia; Male; Maltose; Osteomalacia; Treatment Outcome

Ferric carboxymaltose (FCM) is a novel iron formulation increasingly prescribed due to its effectiveness and fast infusion time. FCM administration can cause an asymptomatic hypophosphataemia secondary to fibroblast growth factor 23 (FGF23) dysregulation. In patients with chronic iron needs, however, a severe, long-lasting hypophosphataemia can lead to osteomalacia with associated bone pain. Lack of awareness of this complication results in delayed time to diagnosis and significant morbidity. We report a case of a patient with Crohn's disease and chronic iron-deficiency anaemia receiving multiple doses of FCM who developed severe hypophosphataemic osteomalacia with urinary phosphate loss and increased FGF23. FGF23 excess and osteomalacia resolved only months after FCM discontinuation and aggressive phosphate repletion. Potential mechanisms of FGF23 dysregulation are discussed, with the aim of raising awareness of this significant side effect for prescribers of chronic intravenous iron supplementation, and to help guide future studies to determine the safety of FCM in all patient populations.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Crohn Disease; Diagnosis, Differential; Ferric Compounds; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypophosphatemia; Male; Maltose; Middle Aged; Osteomalacia; Phosphates; Treatment Outcome

Topics: Administration, Intravenous; Anti-Inflammatory Agents; Biopsy; Crohn Disease; Digestive System Surgical Procedures; Drug Therapy, Combination; Femoral Neck Fractures; Ferric Compounds; Gastrointestinal Agents; Hematinics; Humans; Hypophosphatemia; Hypophosphatemia, Familial; Magnetic Resonance Imaging; Male; Maltose; Middle Aged; Osteomalacia; Postoperative Hemorrhage