OBJECTIVES : To explore the association between PPI use and osteoporotic bone fracture. Specifically, we investigate any use, cumulative use, dose, recent use, and regular use of PPIs are associated with a increased risk of bone fracture.

METHODS : The nested case-control study was conducted using insurance claims data in the Korea National Health Insurance Service. Among people treated with PPIs or H2RAs under the diagnosis codes of PUD and GERD, cases were defined as patients who experienced osteoporotic fracture. For each case, up to five controls were matched on sex, age, bisphosphonate use, cohort entry date and follow-up duration. Conditional logistic regression models were employed to estimate odds ratios.

RESULTS : Subjects were 59,240 matched cases and 296,200 matched controls. 78.0% of total subjects were female. During the follow-up period, subjects administered with any PPI showed higher risk of fracture (OR 1.11; 95% CI: 1.08 - 1.13) compared to those who didn't take it. This result was statistically significant. Moreover, there was a higher risk of fracture in the greater cumulative number of days of PPI administration (p for trend <.0001). Dividing the one year period by 4 quarters, subjects administered with PPI for four weeks or more in all quarters showed higher risk of fracture (OR 1.37; 95% CI: 1.26 - 1.50). The risk of fracture by PPI use tended to increase in highly aged subjects.

CONCLUSIONS : PPI administration in older age groups increased the risk of bone fracture. Moreover, it was found that continued PPI administration had a greater effect on increasing the risk. Therefore, it is required to check medical histories of patients before PPI administration. Especially, for elderly patients requiring long-term PPI administration, the risk of PPI use should be informed and needless administration should be limited.