Korean J Intern Med.  2020 Sep;35(5):1084-1093. 10.3904/kjim.2018.331.

Proton pump inhibitor use is associated with hip fracture development: a nationwide populationbased cohort study

  • 1Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 2Department of Digital Health, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Korea
  • 3Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
  • 4Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, Korea
  • 5Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 6Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 7Department of Gastroenterology, Mediplex Sejong Hospital, Incheon, Korea
  • 8Division of Gastroenterology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Ilsan, Korea
  • 9Department of Gastroenterology, Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
  • 10Big Data Steering Department, National Health Insurance Service, Wonju, Korea


Effect of proton pump inhibitor (PPI) use on the risk of hip fracture is controversial. This study aimed to clarify the association between PPI use and hip fracture risk using a large cohort.
This study recruited participants from the nationwide cohort (n =1,025,340). After exclusion of participants who had hip fractures or were aged less than 40 years during the baseline period (2002 to 2004), 371,806 participants were followed to 2013. Participants prescribed PPIs for more than 90 days during baseline period were defined as users. Fracture cases were defined when participants were hospitalized with claims of a hip fracture.
During 4,159,343 person-years of follow-up, fractures developed more often in PPI users than in nonusers (relative risk [RR], 1.787; 95% confidence interval [CI], 1.260 to 2.534; p = 0.002). The results persisted after adjusting for age, sex, and many drugs relevant to osteoporosis or influential in bone health. Furthermore, fracture risk associated with PPI use increased with duration of use ( p trend < 0.001). The fully adjusted RRs of hip fracture development were 1.350 (95% CI, 1.203 to 1.515) for 1- to 90-day users, 1.487 (95% CI, 0.957 to 2.311) for 91- to 180-day users, and 1.771 (95% CI, 0.931 to 3.368) for > 180-day users. The positive association between PPI use and fracture was also confirmed in a subgroup with health screening data where further adjustment for body mass index, smoking status, alcohol consumption, and physical activity was available (adjusted RR, 2.025; 95% CI, 1.151 to 3.564, p = 0.014). Conclusions: PPI use is associated with hip fracture development.


Drug side effect; Hip fracture; Proton pump inhibitor
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