The association between proton pump inhibitor use and risk of osteoarthritis: a cross-sectional study

Abstract Background Proton pump inhibitors (PPIs) are widely used for managing gastrointestinal conditions, but emerging evidence suggests a potential association with osteoarthritis (OA). This study aims to evaluate the relationship between PPI use and OA, and to investigate whether prolonged PPI use further contributes to OA risk. Methods We performed a cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. PPIs use information was obtained by using prescription medications in the preceding month, and OA status was identified via standard questionnaire. Multivariable regression models were employed to estimate the association between PPIs use and OA after the adjustment for potential confounders. Subgroup analyses were conducted to explore potential interaction effects based on age, gender, race, and body mass index. Results A total of 18,605 participants were included in the analysis, of whom 2,090 had OA. After adjusting for all covariates, multifactorial logistic regression revealed a significant association between PPI use and increased OA risk (OR = 1.855 95%CI = 1.549–2.221, P < 0.001). Notably, a dose-response relationship was identified, with each additional year of PPI use increasing OA risk by 7.6% (OR: 1.076, 95% CI: 1.049–1.103, P < 0.001). Subgroup analyses showed that PPI use was significantly associated with OA risk across all populations, with the exception of young adults, other Hispanic, and other racial groups. Of particular note, in middle-aged and Mexican American subpopulations, prolonged PPI use corresponded with a significant higher OA risk. Conclusions This study demonstrates a significant association between PPI use and an increased risk of OA, with a further risk increment observed with prolonged PPI.