Refractory Denosumab-Induced Hypocalcemia in a High-Risk Patient With Osteoblastic Metastatic Prostate Adenocarcinoma

Jean Damascene Nizeyimana, Lisa Dreessen, Corina Andreescu, Adriaan Duhamel, Siddhartha Lieten, Eric Balti
JCEM Case Reports, Volume 3, Issue 8, August 2025, luaf121
https://doi.org/10.1210/jcemcr/luaf121

Abstract

Denosumab is a frequently used medication, mainly for the treatment of osteoporosis and prevention of skeletal-related events in patients with metastatic cancer. However, the treatment can be associated with adverse events including hypocalcemia.

We discuss the therapeutic challenges of denosumab-induced hypocalcemia in a patient with metastatic prostate adenocarcinoma. This 87-year-old patient presented to the emergency department after being found on the floor with altered mental status. Denosumab had been initiated 3 weeks earlier for stage 4 prostate adenocarcinoma with osteoblastic bone metastatic lesions. Blood analyses showed severe hypocalcemia (3.89 mg/dL [0.97 mmol/L]), which did not improve despite progressive incremental parenteral calcium administration and cholecalciferol supplementation. Management required 64 days of admission and titration of calcitriol. The patient was discharged after stabilizing plasma calcium level. Outpatient palliative care was later initiated because of progressive prostate adenocarcinoma, which ultimately led to the patient's death. Patients with metastatic bone disease, especially when treated with denosumab for prevention of skeletal-related events, present an increased risk of severe and even refractory hypocalcemia. More data are needed for optimal risk stratification of these patients, to identify robust predictors of hypocalcemia and to define the appropriate timing for starting calcium and vitamin D supplementation in high-risk individuals.

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