Do bisphosphonates increase esophageal cancer risk? A meta-analysis.

Abstract

31 Background: Oral bisphosphonates are known to cause severe esophagitis in some users. This has lead to some authors speculating that they may also increase the risk of esophageal cancer. However, studies investigating the association have yielded inconsistent results. The aim of this work is to summarize available data on the magnitude and direction of the association in a meta-analysis. Methods: A standardized search was independently conducted by two investigators from January 1990 through September 2010 on Medline and PubMed. Identified articles that met the exposure and outcome definition were manually reviewed for any additional references. Only full articles that provided risk estimates for the association were eligible for inclusion. The most adjusted risk estimates were abstracted independently by the two authors and synthesized using the random-effects model. A stratified analysis by study design has also been done. All studies were evaluated for publication bias before analysis. Results: Five studies, three case-controls and two cohort studies were eligible for analysis. The combined risk estimate for esophageal cancer was 0.86 (95% CI: 0.62, 1.09). This result remained consistently nonsignificant among the case control studies with a risk estimate of 1.26 (95% CI: 0.94, 1.57). However, there was a significant decrease in the risk of esophageal cancer among the cohort studies with a risk ratio of 0.35 (95% CI: 0.00, 0.71). There was no heterogeneity among the studies by study design. No evidence of publication bias was found, even by study design. Conclusions: This meta-analysis shows that the evidence in support of an association between bisphosphonates and esophageal cancer is lacking. Large studies with appropriate comparison groups, adequate follow-up, robust characterization of the exposure and information on potential confounders are warranted to determine whether bisphosphonates increase esophageal cancer risk. No significant financial relationships to disclose.