Proton pump inhibitor therapy and risk of knee replacement surgery: a general population-based cohort study

C Zeng; T Neogi; A T Chan; J Wei; D Misra; N Lu; H K Choi; G Lei; Y Zhang

doi:10.1016/j.joca.2021.12.010

Proton pump inhibitor therapy and risk of knee replacement surgery: a general population-based cohort study

Osteoarthritis Cartilage. 2022 Apr;30(4):559-569. doi: 10.1016/j.joca.2021.12.010. Epub 2022 Jan 11.

Authors

C Zeng¹, T Neogi², A T Chan³, J Wei⁴, D Misra⁵, N Lu⁶, H K Choi⁷, G Lei⁸, Y Zhang⁹

Affiliations

¹ Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: zengchao@csu.edu.cn.
² Section of Rheumatology, Boston University School of Medicine, Boston, MA, USA. Electronic address: tneogi@bu.edu.
³ Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA. Electronic address: ACHAN@mgh.harvard.edu.
⁴ Health Management Center, Xiangya Hospital, Central South University, Changsha, China. Electronic address: weij1988@csu.edu.cn.
⁵ Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: dmisra@bidmc.harvard.edu.
⁶ Arthritis Research Canada, Richmond, British Columbia, Canada. Electronic address: llu@arthritisresearch.ca.
⁷ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: HCHOI@mgh.harvard.edu.
⁸ Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: lei_guanghua@csu.edu.cn.
⁹ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: yzhang108@mgh.harvard.edu.

Abstract

Objective: Proton pump inhibitors (PPIs) are among the most commonly used medications for patients with osteoarthritis (OA). Various types of PPIs have different impacts on lowering serum magnesium level that may affect knee OA progression. We aimed to compare the risk of clinically relevant endpoint of knee replacement (KR) among initiators of five different PPIs with that among histamine-2 receptor antagonist (H2RA) initiators.

Design: Among patients with knee OA (≥50 years) in The Health Improvement Network database in the UK we conducted five sequential propensity-score matched cohort studies to compare the risk of KR over 5-year among patients who initiated omeprazole (n = 2,672), pantoprazole (n = 664), lansoprazole (n = 3,747), rabeprazole (n = 751), or esomeprazole (n = 827) with those who initiated H2RA.

Results: The prevalence of PPI prescriptions among participants with knee OA increased from 12.7% in 2000-44.0% in 2017. Two-hundred-and-seventy-four KRs (30.8/1,000 person-years) occurred in omeprazole initiators and 230 KRs (25.4/1,000 person-years) in H2RA initiators. Compared with H2RA initiators, the risk of KR was 21% higher in omeprazole initiators (hazard ratio [HR] = 1.21,95% confidence interval [CI]:1.01-1.44). Similar results were observed when pantoprazole use was compared with H2RA use (HR = 1.38,95%CI:1.00-1.90). No such an increased risk of KR was observed among lansoprazole (HR = 1.06,95%CI:0.92-1.23), rabeprazole (HR = 0.97,95%CI:0.73-1.30), or esomeprazole (HR = 0.83,95%CI:0.60-1.15) initiators compared with that among H2RA initiators.

Conclusions: In this population-based cohort study, initiation of omeprazole or pantoprazole use was associated with a higher risk of KR than initiation of H2RA use. This study raises concern regarding an unexpected risk of omeprazole and pantoprazole on accelerating OA progression.

Keywords: Cohort; Knee replacement; Osteoarthritis; Proton pump inhibitor.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Esomeprazole
Humans
Lansoprazole / therapeutic use
Omeprazole / pharmacology
Omeprazole / therapeutic use
Osteoarthritis, Knee* / drug therapy
Pantoprazole / therapeutic use
Proton Pump Inhibitors* / adverse effects
Rabeprazole

Substances

Proton Pump Inhibitors
Lansoprazole
Rabeprazole
Pantoprazole
Omeprazole
Esomeprazole

Abstract

Publication types

MeSH terms

Substances

Grants and funding