Bisphosphonate treatment and risk of esophageal cancer: a meta-analysis of observational studies

The use of bisphosphonates and the risk of esophageal cancer have recently received increasing concern and related studies have yielded controversial results. The present meta-analysis of observational studies shows that no clear association between bisphosphonate treatment and risk of esophageal cancer was observed. Epidemiological evidence suggests that bisphosphonate treatment can increase the risk of esophageal cancer. However, data on this issue are unstable and controversial. We conducted a meta-analysis to provide a quantitative assessment of the association between use of bisphosphonates and risk of esophageal cancer. We searched the Medline and Embase databases up to May 2012 to identify studies related to bisphosphonates and esophageal cancer. Summary effect estimates with 95 % confidence intervals (CI) were derived using a fixed or random effects model, depending on the heterogeneity of the included studies. Seven epidemiologic studies that consisted of four cohort studies and three case-control studies were included in this meta-analysis. In our primary analysis, bisphosphonate treatment was not associated with risk of esophageal cancer in both cohort studies [pooled relative risk (RR) 1.23, 95 % CI 0.79-1.92] and case-control studies [pooled odds ratio (OR) 1.24, 95 % CI 0.98-1.57]. Evidence for the presence of significant heterogeneity was found in cohort studies (p = 0.009, I (2) = 74 %) but not in case-control studies (p = 0.338, I (2) = 7.8 %). In our secondary analysis, no significant increased risk of esophageal cancer was found in alendronate users (pooled RR 1.08, 95 % CI 0.67-1.75 in cohort studies; pooled OR 1.16, 95 % CI 0.82-1.63 in case-control studies). Based on current evidences, bisphosphonate treatment was not significantly associated with excess risk of esophageal cancer.