MON-787 - Severe Prolonged Hypocalcemia Following Denosumab in A Patient with Metastatic Prostate Cancer

Introduction

Denosumab is a monoclonal antibody to receptor activator of nuclear factor κB ligand (RANKL) widely used to prevent skeletal-related events in patients with bone metastases. By inhibiting osteoclast-mediated bone resorption, Denosumab reduces calcium efflux from bone and may precipitate hypocalcemia, particularly in patients with vitamin D deficiency, renal impairment, or impaired parathyroid reserve. Although mild hypocalcemia is common, severe and prolonged cases requiring continuous intravenous calcium replacement are uncommon. We report a case of severe Denosumab-induced hypocalcemia in a patient with metastatic prostate cancer.

Case

A 52-year-old man with metastatic prostate cancer receiving carboplatin and cabazitaxel chemotherapy and palliative radiation to the ribs presented after outpatient laboratory testing revealed severe electrolyte abnormalities. Three weeks earlier, he had received Denosumab 120 mg with chemotherapy. His serum calcium prior to treatment was normal (8.5 mg/dL). On presentation, he was found to have profound hypocalcemia (5.5 mg/dL) with low ionized calcium (3.3 mg/dL) and associated hypophosphatemia ( < 0.9 mg/dL). Laboratory evaluation demonstrated low 25-hydroxyvitamin D (9.8 ng/mL) and markedly elevated parathyroid hormone (322 pg/mL), consistent with secondary hyperparathyroidism. Of note, 25-hydroxyvitamin D was not checked prior to Denosumab administration. Renal function and thyroid studies were normal.

The patient required continuous intravenous calcium gluconate infusion for eight days with frequent rate adjustments. Hypophosphatemia was treated with intravenous followed by oral phosphate. Hypomagnesemia (1.5 mg/dL) was corrected with intravenous magnesium and oral magnesium gluconate. Oral calcium carbonate was escalated to 3000 mg four times daily with vitamin D supplementation (50,000 units twice weekly). Following magnesium repletion and aggressive calcium therapy, corrected calcium improved from a nadir of 7.1 mg/dL to 7.5 mg/dL over three consecutive measurements, and the patient remained asymptomatic.

Conclusion
Denosumab-induced hypocalcemia can be severe and prolonged, particularly in patients with vitamin D deficiency and hypomagnesemia. Patients typically develop severe hypocalcemia two to ten weeks following each Denosumab injection, with the greatest risk occurring during weeks two to five and requiring sustained intravenous and oral replacement. This case highlights the importance of screening for calcium, vitamin D, magnesium, and phosphorus levels in high-risk oncology patients receiving Denosumab.

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