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Abstract: PO1862

Overlooked and Unanticipated: Life-Threatening Hypocalcemia due to Denosumab in a Patient with Prostate Cancer

Session Information

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Vasquez-Rios, George, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Gomez, Johnson Lim, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Chanumolu, Pramodh, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Dijanic, Amanda, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Abramson, Matthew, Icahn School of Medicine at Mount Sinai, New York, New York, United States
Introduction

Denosumab is a monoclonal antibody that inhibits osteoclast-mediated bone resorption by binding to receptor activator of NF-κB ligand, which is upregulated by tumor cells. Despite FDA warning, insidious and severe onset hypocalcemia is a malignant and overlooked complication in patients with advanced CKD.

Case Description

A 77-year-old man with a history of prostate cancer and CKD stage 4 presented to the ED with tremors and numbness in both arms along with perioral dysesthesias. In addition to furosemide and metoprolol, he received his first dose of denosumab 2 weeks prior to presentation, indicated for bone metastasis. Physical examination was remarkable for the Chvostek sign and delayed reflexes in the upper and lower extremities. Lab results were as follows: Na 136 mEq/L, K 4.4 mEq/L, HCO3: 6.4 mEq/L, Cr: 4.8 mg/dL, PO4: 6.1 mg/dL, Ca: 4.8 mg/dL, Mg: 2.6 mg/dL & albumin: 3.5 g/dL. Further studies showed: 25-OH vitamin D: 6.5 (<25 ng/mL), iPTH: 988 (10-55 pg/mL), C-telopeptide: 167 (40-465 pg/mL), ALKP: 243 (44-147 iU/L). Urine calcium-to-creatinine ratio was 0.04, suggestive of minimal calcium excretion. ECG showed prolonged QTc. Given the clinical evidence of severe hypocalcemia and ECG changes, the patient was started on peripheral calcium infusion with hourly iCa2+ measurements to maintain iCa >1 mmol/L and reversal of QTc prolongation. Concomitantly, the patient was treated with calcium carbonate 2500 mg TID, ergocalciferol 50,000 units weekly, and calcitriol 0.5 mcg BID. After 72 hours, his ionized calcium levels stabilized with aggressive oral therapy only. Serum calcium at discharge was 8.2 mg/dL and remained low in the range of 7.5-8.9 for the following 8 weeks.

Discussion

Denosumab has a prolonged elimination half-life (up to 32 days) and therefore, it can induce severe & relapsing hypocalcemia, especially in patients with low vitamin D stores. While patients with creatinine clearance <30 mL/min have been found to be prone to adverse effects, no dose modification has been considered for this therapy. Close monitoring within 14 days after the administration of denosumab and prophylactic therapy with oral calcium and vitamin D could be anticipated in this population.