An Evaluation of the Use of Oral Bisphosphonates and Risk of Esophageal Cancer

Abstract

To evaluate the use of oral bisphosphonates and risk of esophageal cancer. MEDLINE (1948-October 2011) was searched using the terms esophageal cancer, esophageal carcinoma, bisphosphonate, bisphosphonates, etidronate, pamidronate, alendronate, tiludronate, risedronate, zoledronic acid, and ibandronate. Citations from relevant publications were reviewed for additional information. A comprehensive review of the available literature was performed. Two summaries of case reports and 3 observational studies were retrieved and reviewed. Oral bisphosphonates can cause esophageal irritation; therefore, it is biologically plausible that they may increase the risk of esophageal cancer. Although many cases were reported, causality was difficult to determine due to their weak methodology, and subsequent evaluations from national registers did not support an increased risk. Of the 3 observational studies (1 in patients with Barrett's esophagus and 2 using the same patient database), only 1 found an increased risk with use of daily or weekly regimens, and significant limitations were noted in each. Evidence on the use of bisphosphonates and risk of esophageal cancer is weak and conflicting. Additional studies are needed to further evaluate this issue and formulate stronger conclusions. In the meantime, health care professionals should ensure that patients take oral bisphosphonates properly to minimize esophageal irritation, are prescribed regimens that minimize exposure if adherence is difficult, and are evaluated for discontinuation of the drugs if appropriate. For patients at increased risk of esophageal cancer for other health reasons, nonoral bisphosphonates may be considered.