Comparative analysis of the risk of osteoporotic fractures with proton pump inhibitor use and histamine-2 receptor antagonist therapy in elderly women: A nationwide population-based nested case-control study

The influence of proton pump inhibitors (PPIs) on the risk of osteoporotic fractures remains to be elucidated, especially in the Asian population. This study evaluated the risk of osteoporotic fractures in elderly female Korean PPI users compared to histamine-2 receptor antagonist (H2RA) users, as well as the relationship between fractures and the duration, dose, and pattern of use of PPI. We screened a nationwide cohort of elderly Korean women who underwent bone mineral density measurements during their 66-year-old life-transition medical examination between 2009 and 2014. Study subjects included 8903 cases diagnosed with new osteoporotic fractures and 44,515 matched controls (1:5 ratio based on cohort entry date, follow-up duration, and baseline osteoporosis status) without fractures. They were followed up until 2015. Information on the exposure to PPI or H2RA, occurrence of fracture, and covariates were obtained from the Korean National Health Insurance Service data. Covariate-adjusted odds ratio (aOR) and 95% confidence interval (CI) were estimated using conditional logistic regression analysis. PPI use was associated with an increased risk of osteoporotic fractures (aOR: 1.13, 95% CI: 1.07, 1.18) compared with H2RA-only use. Increasing duration of PPI use was positively associated with the risk of osteoporotic fracture [aOR (95% CI) of long-term PPI use (>= 1 year): 1.3 (1.09, 1.56)]. Recent PPI use within the last year was associated with an increased risk of fracture (aOR: 1.31, 95% CI: 1.23, 1.38), whereas remote PPI use was not (aOR: 0.98, 95% CI: 0.92, 1.04). The risk of fracture did not increase with the increasing cumulative PPI dose. Compared with the use of H2RA alone, PPI use was associated with an increased risk of osteoporotic fractures in elderly Korean women, particularly among those who had used PPI within the last year or for more than one year.