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

Ann Pharmacother. 2021 Mar;55(3):303-310. doi: 10.1177/1060028020953501. Epub 2020 Aug 27.

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.

Keywords: bisphosphonate; hypercalcemia; pamidronate; renal dysfunction; zoledronic acid.

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Aged, 80 and over
  • Diphosphonates / pharmacology
  • Diphosphonates / therapeutic use*
  • Female
  • Humans
  • Hypercalcemia / drug therapy*
  • Kidney Diseases / chemically induced*
  • Male
  • Middle Aged
  • Prospective Studies
  • Retrospective Studies

Substances

  • Diphosphonates