Severe, Prolonged, Denosumab-Induced Hypocalcemia With Recovery After 111 Days Of High-Dose Calcium Supplementation

ABSTRACT Objective: Denosumab is a monoclonal antibody commonly used for the prevention of skeletal-related events in patients with bone metastases from solid tumors. Hypocalcemia is a known adverse effect with denosumab, and we present an unusual case where 2 hypocalcemic events occurred after 1 denosumab treatment. Methods: A 76-year-old man recently diagnosed with prostate cancer with bone metastasis was given 120 mg denosumab subcutaneously due to extensive bone disease. Results: The patient experienced denosumab-induced hypocalcemia induced by a single denosumab dose which was resolved after 14 days of multiple doses of intravenous calcium gluconate and oral calcium and vitamin D replacement. However, the patient returned with acute kidney injury and severe hypocalcemia (corrected calcium of 6.9 mg/dL) without any additional dose of denosumab. The recovery following the second episode of hypocalcemia was much longer than the initial episode in this patient. Conclusion: To our knowledge, this is the first reported case of an additional episode of hypocalcemia following a single denosumab dose. This case highlights the importance of close monitoring of renal function and serum electrolytes following the resolution of denosumab-induced hypocalcemia. Abbreviations: 25(OH)D = 25-hydroxyvitamin D; AKI = acute kidney injury; CI = confidence interval; IV = intravenous; PTH = parathyroid hormone; SRE = skeletal-related event; ZA = zoledronic acid