Severe hypophosphataemia following denosumab administration successfully managed using a calcimimetic agent

BMJ Case Rep. 2025 Jan 8;18(1):e263129. doi: 10.1136/bcr-2024-263129.

Abstract

Denosumab, an anti-RANKL antibody, induces bone metabolism to a low-turnover bone status by arresting osteoclast activity. Frequent adverse events include infusion reactions, fever and hypocalcaemia but not hypophosphataemia. We report a case of severe hypophosphataemia associated with secondary hyperparathyroidism following denosumab administration in a young boy with recurrent osteosarcoma who was successfully treated with evocalcet. He developed hypocalcaemia and severe refractory hypophosphataemia after receiving denosumab for bone metastases despite calcium, cholecalciferol and phosphorus supplementation. Laboratory data revealed secondary hyperparathyroidism due to denosumab-induced hypocalcaemia as the cause of hypophosphataemia. Evocalcet contributed to the normalised parathyroid hormone and phosphorus levels, allowing the discontinuation of phosphorus supplementation. This case highlights the complexity of managing electrolyte imbalances induced by bone-modifying agents, such as denosumab, underscoring the importance of monitoring bone metabolism markers and the potential effectiveness of evocalcet in managing drug-induced secondary hyperparathyroidism and hypophosphataemia.

Keywords: Hypophosphatemia; Pancreatic cancer.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Bone Density Conservation Agents* / adverse effects
  • Bone Density Conservation Agents* / therapeutic use
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary
  • Calcimimetic Agents* / therapeutic use
  • Denosumab* / adverse effects
  • Denosumab* / therapeutic use
  • Humans
  • Hyperparathyroidism, Secondary* / drug therapy
  • Hyperparathyroidism, Secondary* / etiology
  • Hypocalcemia* / chemically induced
  • Hypocalcemia* / drug therapy
  • Hypophosphatemia* / chemically induced
  • Hypophosphatemia* / drug therapy
  • Male
  • Osteosarcoma / drug therapy
  • Treatment Outcome

Substances

  • Denosumab
  • Calcimimetic Agents
  • Bone Density Conservation Agents