Safety of Intravenous Bisphosphonates for the Treatment of Hypercalcemia in Patients With Preexisting Renal Dysfunction

Abstract

Background Although intravenous (IV) bisphosphonates are first-line medications for the management of hypercalcemia, studies examining their use in patients with preexisting renal dysfunction are limited. Objective The objective of this study is to describe the safety and efficacy of pamidronate and zoledronic acid in the treatment of hypercalcemia in patients with baseline renal dysfunction. Methods A retrospective analysis was conducted of IV pamidronate and zoledronic acid in adult patients with hypercalcemia and creatinine clearance (CrCl) <60 mL/min. The primary endpoint was incidence of all-grade serum creatinine (SCr) elevations. Secondary endpoints included refractory hypercalcemia, hypocalcemia, osteonecrosis of the jaw (ONJ), corrected serum calcium (CSC) decrease ≥1.0 mg/dL by day 7 of bisphosphonate administration, and normalization of CSC ≤10.5 mg/dL by days 10 and 30. Results A total of 113 patients were included (n = 55 pamidronate, n = 58 zoledronic acid). The primary endpoint of all-grade SCr elevation occurred in 28 (24.8%) patients. Grades 3/4 SCr elevations occurred in 10.9% of patients treated with pamidronate and 1.7% of patients receiving zoledronic acid. Approximately 16% and 14% of patients developed grades 1 and 2 hypocalcemia, respectively, and there were no cases of ONJ. Overall, 64.6% of patients achieved normalization of CSC by day 10, and there were no statistical differences between bisphosphonate type and renal function. Conclusions and Relevance The analysis suggests an association between IV bisphosphonates and increased rates of SCr elevations among patients with preexisting renal dysfunction. Future prospective studies are necessary to elucidate these findings.