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Exposure to oral bisphosphonates and risk of gastrointestinal cancer



Few studies have explored the association of oral bisphosphonate exposure and gastrointestinal cancer within Asian populations. In this study, we investigated 45,397 Korean women from the nationwide population-based cohort from 2002 to 2013. Oral bisphosphonate exposure did not appear to be associated with elevated or reduced risk for gastrointestinal cancer.


While several studies suggested increased risk in upper gastrointestinal (GI) cancer or reduced risk in colorectal cancer upon bisphosphonate exposure, the association is less explored within Asian populations. We investigated the effect of oral bisphosphonate exposure on the risk of GI cancers within a nationwide population-based cohort.


This study used two separate cohorts. The first cohort included 45,397 women aged 60 years or older from the National Health Insurance Service-Health Screening Cohort during 2002–2013. Participants were classified into bisphosphonate users and non-users based on drug exposure during 2002–2007, and followed-up from the index date of January 1, 2008. The second cohort included 25,665 newly diagnosed osteoporosis patients who started taking oral bisphosphonate during 2003–2008. After 4 years of drug exposure period, patients were separated into quartiles based on cumulative oral bisphosphonate exposure. Participants were followed-up until December 31, 2013 for GI cancer, stomach cancer, and colorectal cancer. Cox proportional hazard regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the cancer risks.


Compared to bisphosphonate non-users, no significant risk difference was observed among bisphosphonate users on GI (HR 1.06; 95% CI 0.87–1.28), stomach (HR 1.11; 95% CI 0.85–1.47) and colorectal cancers (HR 1.04; 95% CI 0.79–1.37). Among bisphosphonate users, increasing doses of bisphosphonate exposure was not associated with elevated or reduced risk for GI cancer (p for trend 0.573).


Oral bisphosphonate use did not appear to be associated with elevated or reduced risk for GI cancers.

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This study was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (grant number: 2017R1D1A1B03033721) and the Seoul National University Research Fund (grant number: 04-2018-0370). S.C. received a grant from the Brain Korea 21-Plus Education Program from the National Research Foundation of Korea.

Author information

D.C., S.C., J.C. and S.M.P. contributed to the conception and design, analysis and interpretation of data, critical revision for important intellectual content, and final approval of the article. D.C., S.C., and J.C. contributed to the drafting of the article. D.C. conducted collection and assembly of the data. All authors approved the final copy of the article. S.M.P. is the corresponding author and had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Correspondence to S. M. Park.

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None of the funders had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Choi, D., Choi, S., Chang, J. et al. Exposure to oral bisphosphonates and risk of gastrointestinal cancer. Osteoporos Int (2020). https://doi.org/10.1007/s00198-020-05327-x

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  • Bisphosphonate
  • Colorectal cancer
  • Gastrointestinal cancer
  • Stomach cancer