Increased risk of knee osteoarthritis in patients using oral N-acetylcysteine: a nationwide cohort study

Background Knee osteoarthritis (OA) is known to be a progressive degenerative disorder; however, recent evidence suggests that inflammatory mediators contribute to cartilage degradation. Studies have reported that N-acetylcysteine (NAC) had a promising effect on the reduction of the synthesis of proinflammatory and structural mediators by synovial cells. Given the lack of relevant clinical trials, we conducted this study to determine the relationship between NAC use and risk of knee OA. Methods We designed a retrospective cohort study from 2000 to 2013. Patients who received oral NAC over 28 days within 1 year after the first prescription were defined as the case group, whereas those without NAC use were considered as candidates of the control group. We adopted 1:4 propensity-score matching by age, sex, index year, and comorbidities to obtain the control group. The primary outcome was a new diagnosis of knee OA during the follow-up period. Results Our study sample comprised 12,928 people who used NAC and 51,715 NAC nonusers. NAC users had a significantly higher incidence of osteoarthritis (adjusted hazard ratio: 1.42, P P Conclusions Long-term use of oral NAC is associated with a higher risk of knee OA.