Knee osteoarthritis (OA) is known as a progressive degenerative disorder, but recent evidence suggests that inflammatory mediators contribute to cartilage degradation. N-acetylcysteine (NAC) is an antioxidant that can directly scavenge reactive oxygen species. According to basic studies, NAC had an apparent effect on reducing the synthesis of proinflammatory and structural mediators by synovial cells. In contrast, chondrocyte in osteoarthritic cartilage was found significantly lower intracellular p53 expression. NAC was also reported to decrease p53 expression through reduction of oxidative DNA damage. Due to lacking clinical trials, we conducted this study to determine the relationship between NAC use and risk of knee OA.

We designed a retrospective cohort study using the Taiwan's Longitudinal Health Insurance Database from 2000 to 2013. Patients receiving oral form N-acetylcysteine over 28 days within one year after first prescription were defined as case group, whereas those without N-acetylcysteine use were considered as candidates of control group. We adopted a 1:10 propensity score matching by age, sex, index year and comorbidities to consist the control group. Patients with previous history of knee operation (total knee replacement and anterior cruciate ligament reconstruction), bed-ridden status, and less than 20 years old were excluded. The primary outcome was a new diagnosis of knee OA during follow-up period.

Our study samples consist of 7726 using NAC subject and 77260 non-used NAC subject. People with NAC use have significantly higher incidence of osteoarthritis (adjusted HR: 1.39, P<0.0001) (Fig. 1). In addition, analyses stratified by age group and sex, all subgroups showed significantly higher incidence of osteoarthritis (P<0.0001) in NAC users (Table 1).

Patients who take oral N-acetylcysteine more than 28 days per year have higher risk of developing knee osteoarthritis.