Meta-analysis: oral bisphosphonates and the risk of oesophageal cancer

Aliment Pharmacol Ther. 2012 Oct;36(8):708-16. doi: 10.1111/apt.12041. Epub 2012 Sep 11.


Background: Bisphoshonates, which are used in the treatment and prevention of osteoporosis, have recently been implicated in the development of oesophageal cancer; however, studies report conflicting data.

Aim: To conduct a meta-analysis of studies reporting on the association between bisphosphonates and oesophageal cancer to quantify the relationship.

Methods: A search was conducted through Medline, PubMed, Embase and Current Contents Connect to 2 August 2012. We calculated pooled odds ratios and 95% CIs using a random effects model for the risk of oesophageal cancer associated with exposure to bisphosphonates, as well as for the different periods of exposure.

Results: Seven studies, with 19 700 oesophageal cancer cases, met our inclusion criteria. We found a positive relationship between exposure to bisphosphonates and oesophageal cancer, with an odds ratio (OR) of 1.74 with a 95% CI of 1.19-2.55. Heterogeneity was observed (I(2 ) = 85%, P < 0.001). Publication bias was not present. An increased risk of oesophageal cancer was also found in the group exposed to bisphosphonates for a longer period of time, compared with the group who experienced a shorter period of exposure (OR 2.32; 95% CI 1.57-3.43 vs. OR 1.35; 95% CI 0.77-2.39). An increased risk was associated with exposure to Etidronate (OR 1.58; 95% CI 1.12-2.24), but not to Aledronate.

Conclusions: Exposure to bisphosphonates may be associated with an increased risk of oesophageal cancer. More studies are needed to confirm the relationship.

Publication types

  • Meta-Analysis

MeSH terms

  • Administration, Oral
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects*
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects*
  • Esophageal Neoplasms / chemically induced*
  • Humans
  • Models, Theoretical
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Risk


  • Bone Density Conservation Agents
  • Diphosphonates