Severe osteomalacia and insufficiency fractures due to combined iron induced hypophosphataemia and malabsorption-related calcium deficiency in a patient with Crohn's disease: A case report

Ferric carboxymaltose (FCM) induced hypophosphataemia is increasingly recognized as a clinically relevant adverse effect of intravenous iron therapy. In severe and prolonged cases, phosphate depletion may result in osteomalacia, insufficiency fractures, and significant functional impairment. However, longitudinal bone mineral density outcomes after treatment remain poorly documented. We report a 32-year-old woman with Crohn's disease and chronic iron deficiency anaemia who developed severe hypophosphataemia following repeated FCM infusions. She presented with profound muscle weakness, diffuse bone pain, wheelchair dependence, multiple atraumatic insufficiency fractures, severe hypophosphataemia (0.24 mmol/L), secondary hyperparathyroidism, and markedly reduced bone mineral density (T-score at femoral neck (FN) and lumbar spine (LS) −3.7 and −3.5 respectively). FCM was discontinued and oral phosphate, calcium, and vitamin D supplementation was initiated, followed by active vitamin D and intravenous calcium. Over follow-up, the patient experienced near-complete functional recovery, progressing from wheelchair dependence to independent ambulation. DXA demonstrated an exceptional skeletal recovery, with femoral neck T-score improving from −3.7 to +3.2 (+186%) and lumbar spine T-score from −3.5 to +1.0 (+128%). This case highlights the possibility of complete recovery and excellent outcomes if drug-induced hypophosphatemia is appropriately recognized and managed. While iron-induced FGF23-mediated hypophosphataemic osteomalacia likely played a major role, additional contributing factors were present, including calcium malabsorption related to inflammatory bowel disease. The magnitude and rapidity of BMD improvement following treatment largely exceed what is typically reported in FCM-induced or other forms of osteomalacia, and illustrates the remarkable reversibility of severe acquired osteomalacia.