Differences in nephrotoxicity of intravenous bisphosphonates for the treatment of malignancy-related bone disease

Renal dysfunction is a particularly problematic adverse event that requires additional management and can prohibit the use of certain medications. Due to their renal uptake and elimination, some bisphosphonates can cause nephrotoxicity when used for the treatment of skeletal-related events in patients with bone metastases. However, clinical studies and post-marketing experience indicate that renal effects do not appear to be the same for all bisphosphonates. Zoledronic acid and pamidronate appear to be associated with a greater risk of renal toxicity, especially when given in high doses or over short infusion times. In contrast, high loading doses of intravenous ibandronate (3 x 6 mg given on days 1-3) have shown no additional renal safety concerns, and intravenous ibandronate 6 mg appears to have a renal safety profile comparable to placebo. This paper reviews the renal safety of intravenously administered bisphosphonates and makes some suggestions, based on preclinical and clinical data, as to why renal safety profiles may differ.