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J Gastroenterol. 2013 Sep;48(9):1016-22. doi: 10.1007/s00535-012-0722-9. Epub 2013 Jan 11.

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

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Clinical Epidemiology Division, Medical Research Collaborating Center, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea.



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.

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