Journal of Gastroenterology

, Volume 48, Issue 9, pp 1016–1022 | Cite as

A population-based case–control study: proton pump inhibition and risk of hip fracture by use of bisphosphonate

  • Joongyub Lee
  • KyungEun Youn
  • Nam-Kyong Choi
  • Jin-Ho Lee
  • DongYoon Kang
  • Hong-Ji Song
  • Byung-Joo ParkEmail author
Original Article—Alimentary Tract



Studies on the risk of osteoporotic fractures related to the use of proton pump inhibitors (PPIs) have been inconsistent. One recent cohort study reported that there was an interaction between PPIs and bisphosphonates (BPs). Thus we performed a case–control study aimed at evaluating the risk of hip fractures related to PPIs and exploring the interaction between PPIs and BPs.


A case–control study was performed using the Korean Health Insurance Review and Assessment Service database from 2005 January to 2006 June. The cases were all incident hip fractures identified from July 2005 to June 2006, and up to four controls were matched to each case by age, gender, and osteoporosis. Conditional logistic regression was used to calculate the adjusted odds ratio (aOR) and its 95 % confidence intervals.


A total of 24,710 cases were identified and 98,642 controls were matched to the cases. The aOR and its 95 % CI of hip fractures related to the use of PPIs was 1.34 (95 % CI 1.24–1.44). When the study participants were stratified according to BP use, the aOR was 1.30 (95 % CI 1.19–1.42) in BP non-users, which was significantly different from the 1.71 (95 % CI 1.31–2.23) of BP users. Only BP users showed a decreasing tendency toward fracture risk as exposure to PPI became less recent, and a trend of increasing risk with increasing cumulative doses.


Our results suggest that the mechanism for increased risk of hip fracture by PPIs may arise mainly from interaction of BP and PPIs.


Proton pump inhibitor Hip fracture Bisphosphonate 



This study was supported by a grant from the Korean Food and Drug Administration (07072KFDA224)

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Joongyub Lee
    • 1
  • KyungEun Youn
    • 2
  • Nam-Kyong Choi
    • 1
    • 6
  • Jin-Ho Lee
    • 3
  • DongYoon Kang
    • 4
  • Hong-Ji Song
    • 5
  • Byung-Joo Park
    • 1
    • 4
    Email author
  1. 1.Clinical Epidemiology Division, Medical Research Collaborating CenterSeoul National University Hospital and Seoul National University College of MedicineSeoulKorea
  2. 2.Pharmaceutical Management DivisionPharmaceutical Safety Bureau, Korea Food and Drug AdministrationCheongwongunKorea
  3. 3.Department of Internal Medicine, School of MedicineDongguk UniversitySeoulKorea
  4. 4.Department of Preventive MedicineSeoul National University College of MedicineSeoulKorea
  5. 5.Department of Family Medicine, College of MedicineHallym UniversityChuncheonKorea
  6. 6.Institute of Environmental MedicineSeoul National University Medical Research CenterSeoulKorea

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