Denosumab-Associated Severe Symptomatic Hypocalcemia in a Patient with Multiple Myeloma and AKI

Introduction: Denosumab, a human monoclonal antibody has several FDA-approved indications including treatment of hypercalcemia of malignancy. Hypocalcemia is a known side effect of this medication however severe symptomatic hypocalcemia has been rarely described in patients with hypercalcemia of malignancy. We present a case of severe symptomatic hypocalcemia following a single dose of Denosumab in a patient with AKI and hypercalcemia from multiple myeloma. Case Description: 78-year-old male with recent history of multiple myeloma, AKI and hypercalcemia presented to our hospital for abdominal discomfort, back pain, tremors and confusion. Admission labs were significant for severely low serum calcium (SCa) level of 4.8 mg/dL and an elevated serum creatinine (SCr) level of 4.06 mg/dL. Two weeks prior to current presentation, our patient was hospitalized for back pain, AKI and hypercalcemia. During that hospital stay, patient was found to have multiple myeloma on bone marrow biopsy. Scr on that admission was elevated at 2.56 mg/dL and SCa was elevated at 12.0 mg/dL. Patient initially received two doses of calcitonin however as serum calcium remained elevated a dose of Denosumab was administered. SCa normalized to 8.9 mg/dL on discharge. During this hospital stay, patient received multiple doses of intravenous calcium with daily oral calcium and calcitriol therapy for several days for management of persistent hypocalcemia. SCa finally improved to 8.4 mg/dL on discharge. Pt. was discharged on oral calcium and calcitriol therapy with close outpatient monitoring of SCa. Discussion: Our patient with AKI and hypercalcemia in setting of multiple myeloma developed severe symptomatic hypocalcemia following a single dose of Denosumab treatment. Our patient required prolonged hospitalization for management of severe and persistent hypocalcemia. Based on our experience, we recommend caution with Denosumab use in patients with AKI and hypercalcemia of malignancy. We also recommend very close outpatient monitoring of SCa following Denosumab treatment in this patient population.