Systematic Review
Knee osteoarthritis (KOA), a debilitating chronic degenerative joint disease, substantially compromises patients’ functional capacity and quality of life. Although physical activity (PA) has been recognised as a modifiable risk factor in the development of KOA, its potential protective role remains debated. To clarify this clinical uncertainty, we conducted a rigorous systematic review and meta-analysis to comprehensively assess the association between PA levels and the risk of incident KOA./r/nWe systematically searched PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science databases for published observational studies on the association between PA and knee osteoarthritis. Following the PRISMA guidelines, we selected English literature from inception to publication on 21 September 2024, and assessed study quality according to the Newcastle-Ottawa scale. Our protocol is available on PROSPERO./r/nOur systematic screening identified 14 eligible observational studies (13 cohort studies and one case-control study) involving 507 696 participants with 27 412 incident cases of KOA. A pooled analysis comparing levels of PA intensity showed a 26% increased risk of knee OA for high PA compared with moderate PA (relative risk (RR) = 1.26; 95% CI = 1.17-1.37). In contrast, neither high PA (RR = 1.02; 95% CI = 0.84-1.23) nor moderate PA (RR = 0.94; 95% CI = 0.84-1.05) showed protective effects compared with low PA reference groups. Stratified analyses showed nonsignificant associations in cohort studies (RR = 1.06; 95% CI = 0.87-1.29) compared with case-control studies (RR = 0.41; 95% CI = 0.20-0.83). Notably, regional subgroup analyses showed comparable PA-related risks between European (RR = 1.01; 95% CI = 0.74-1.38) and North American populations (RR = 1.03; 95% CI = 0.81-1.31). Crucially, gender-stratified analyses demonstrated no significant differential risk in males (RR = 1.20; 95% CI = 0.54-2.70) vs. females (RR = 0.73; 95% CI = 0.29-1.82)./r/nThis systematic review comprehensively demonstrated a dose-dependent relationship between physical activity intensity and the risk of knee osteoarthritis. Our meta-analysis showed that high PA levels significantly increased the risk of knee osteoarthritis compared with moderate PA. In addition, limited evidence suggested that exceeding international PA guidelines may increase the risk of osteoarthritis (RR = 1.18; 95% CI = 1.02-1.35). However, future studies need to be executed to further define the type of activity, optimal dose and duration required to effectively reduce the risk of knee osteoarthritis./r/nPROSPERO: CRD42024600175.