title: Bisphosphonates and evidence for association with esophageal and gastric cancer: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Concerns have been raised about a possible link between bisphosphonate use, and in particular alendronate, and upper gastrointestinal (UGI) cancer. A number of epidemiological studies have been published with conflicting results. We conducted a systematic review and meta-analysis of observational studies, to determine the risk of esophageal and gastric cancer in users of bisphosphonates compared with non-users.
  
  
  METHODS
  We searched PubMed, MEDLINE, EMBASE, Web of Knowledge and Cochrane Database of Systematic Reviews for studies investigating bisphosphonates and esophageal or gastric cancer. We calculated pooled ORs and 95% CIs for the risk of esophageal or gastric cancer in bisphosphonate users compared with non-users. We performed a sensitivity analysis of alendronate as this was the most common single drug studied and is also the most widely used in clinical practice.
  
  
  RESULTS
  11 studies (from 10 papers) examining bisphosphonate exposure and UGI cancer (gastric and esophageal), met our inclusion criteria. All studies were retrospective, 6/11 (55%) case-control and 5/11(45%) cohort, and carried out using data from 5 longitudinal clinical databases. Combining 5 studies (1 from each database), we found no increased risk, OR 1.11 (95% CI 0.97 to 1.27) of esophageal cancer in bisphosphonate users compared with non-users and no increased risk of gastric cancer in bisphosphonate users, OR 0.96 (95% CI 0.82 to 1.12).
  
  
  CONCLUSIONS
  This is the fourth and most detailed meta-analysis on this topic. We have not identified any compelling evidence for a significantly raised risk of esophageal cancer or gastric cancer in male and female patients prescribed bisphosphonates.
authors.affiliation: Department of Primary Care and Public Health Sciences, King's College London, London, UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: Wright
authors.affiliation: Department of Primary Care and Public Health Sciences, King's College London, London, UK.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Schofield
authors.affiliation: Department of Primary Care and Public Health Sciences, King's College London, London, UK.
authors.forename: Mariam
authors.initials: M
authors.lastname: Molokhia
mesh_terms: D019386:Alendronate / Q000009:adverse effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D004164:Diphosphonates / Q000009:adverse effects*; D004938:Esophageal Neoplasms / Q000209:etiology*; D006801:Humans; D013274:Stomach Neoplasms / Q000209:etiology*
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D019386:Alendronate
keywords: RHEUMATOLOGY