SUN-765 - Severe Prolonged Asymptomatic Hypocalcemia Following First-Dose Denosumab in Metastatic Prostate Cancer with Extensive Osteoblastic Disease

Severe Prolonged Asymptomatic Hypocalcemia Following First-Dose Denosumab in Metastatic Prostate Cancer with Extensive Osteoblastic Disease

BACKGROUND
Denosumab is used to prevent skeletal-related events in metastatic prostate cancer. Hypocalcemia is a recognized adverse effect and is usually mild. We present a case of severe and prolonged asymptomatic hypocalcemia in a patient with extensive osteoblastic disease from metastatic prostate cancer.

CASE PRESENTATION
A 92-year-old man with metastatic prostate cancer and extensive diffuse osseous metastases presented to the ED for evaluation of chest pain. Laboratory workup incidentally revealed rapidly progressive hypocalcemia occurring three days after his first dose of denosumab 120 mg. Baseline-corrected calcium prior to denosumab administration was low-normal (8.7 mg/dL), with preserved renal function. Prostate-specific antigen and alkaline phosphatase (ALP) were markedly elevated at 458 ng/mL and 1,391 IU/L (40-129 IU/L), respectively, reflecting significant osteoblastic activity.

Hypocalcemia progressed rapidly, reaching a nadir corrected calcium level of 5.7 mg/dL and an ionized calcium level of 0.78 mmol/L (1.09-1.30 mmol/L) by day five post-injection. Further evaluation revealed severe vitamin D deficiency 12 ng/mL (30-100 ng/mL) and parathyroid hormone 561 pg/mL (18-59 pg/mL), consistent with secondary hyperparathyroidism. Despite aggressive calcium repletion with repeated intravenous bolus and continuous calcium gluconate infusions, high-dose oral calcium, calcitriol, and vitamin D therapy, severe hypocalcemia persisted for 12 days. Remarkably, the patient remained asymptomatic throughout, with no QTc prolongation on serial ECG monitoring. Calcium levels remained low at discharge (corrected calcium 7.5 mg/dL, ionized calcium 0.97 mmol/L) but normalized on outpatient follow-up in 1 month with continued high-dose calcium, calcitriol, and vitamin D supplementation.

CONCLUSION
This case illustrates severe, prolonged, asymptomatic hypocalcemia following a single dose of denosumab. Extensive metastatic osteoblastic disease, denoted by markedly elevated ALP, vitamin D deficiency, and advanced age, predisposed this patient to a hungry bone-like state driven by abrupt osteoclast inhibition and rapid skeletal calcium uptake by osteoblasts. Pretreatment assessment of calcium and vitamin D status, along with consideration of aggressive preemptive supplementation and close monitoring, should be warranted in high-risk patients receiving denosumab.

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