METHODS: This systematic review and meta-analysis identified eligible studies from seven electronic databases and three registries. Longitudinal cohort studies or randomised controlled trials evaluating participants who developed incident symptomatic and/or radiographic KOA were included. Two independent reviewers completed data screening and extraction. Estimates were pooled using a random effects model and reported as odds ratio (OR), hazard ratio (HR), or risk ratio (RR) and corresponding 95% confidence intervals (95% CI). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to determine the certainty of evidence. Population attributable fractions (PAFs) were calculated, including risk factors significantly associated with radiographic KOA based on the pooled meta-analysis and where we could determine communality scores using existing clinical datasets.

RESULTS: We identified 132 studies evaluating >150 risk factors. Higher body mass index (BMI), previous knee injury, older age and high bone mineral density were associated with an increased risk of incident radiographic KOA based on the pooled analysis [OR (95% CI): 1.56 (1.25, 1.95), 3.02 (1.93, 4.71), 1.15 (1.00, 1.33) and 1.82 (1.12, 2.94), respectively], with moderate-to-high certainty. Two risk factors (overweight/obesity and previous knee injury) accounted for 14% of incident radiographic KOA. Other modifiable risk factors including occupational physical activity also contribute to radiographic or symptomatic KOA.

CONCLUSION: Novel strategies addressing known modifiable risk factors including overweight/obesity, knee injuries and occupational physical activity are needed to reduce overall burden of KOA.