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Association of Proton Pump Inhibitor Use and Risk of Fracture Based on the National Health Insurance Sample Cohort Database (2002~2013)
Korean J Clin Pharm 2019;29(3):147-155
Published online September 30, 2019
© 2019 Korean College of Clinical Pharmacy.

Jong Joo Kim1, Eun Jin Jang2, Junwoo Cho3, and Hyun Soon Sohn4*

1Pharmaceutical Information Research Institute, Cha University, Gyeonggi-do 13488, Republic of Korea
2Collage of Natural Science, Andong National University, Gyeongsangbuk-do 36729, Republic of Korea
3Collage of Natural Science, Kyungpook National University, Daegu-si 41566, Republic of Korea
4Collage of Pharmacy, CHA University, Gyeonggi-do 13488, Republic of Korea
Correspondence to: #Equally contributed as first authors
Hyun Soon Sohn, Collage of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Republic of Korea
Tel: +82-31-881- 7171 FAX: +82-31-881-7077 E-mail:
Received May 1, 2019; Revised June 12, 2019; Accepted June 20, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objectives: The purpose of this study was to investigate the association between fracture risk and proton pump inhibitor (PPI) use to establish evidence for defining high-risk groups of fracture among PPI users. Methods: A case-control study was performed using the National Health Insurance Sample Cohort Database from January 2002 to December 2013. The cases included all incidences of major fractures identified from January 2011 to December 2013, and up to four controls were matched to each case by age, gender, osteoporosis, and Charlson comorbidity index. Conditional logistic regression was used to calculate the adjusted odds ratio (aOR) and associated 95% confidence interval (CI). Results: Overall, 14,295 cases were identified, and 63,435 controls were matched to the cases. The aOR of fractures related to the use of PPIs was 1.06 (95% CI: 1.01-1.11). There was a statistically significant association between fracture and PPI use within 3 months of the last dose, and a trend of increasing fracture risk with increasing cumulative PPI dose. The risk of fracture was significantly higher in patients who took PPIs for more than 1 year during the 2-year observation period. Conclusion: Patients who have been using PPIs for more than 1 year should be warned about the risk of fracture during or at least 3 months after discontinuing the PPI.
Keywords : Proton pump inhibitor, fracture, case-control, National Health Insurance Sample Cohort Database, population based

September 2019, 29 (3)
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