Abstract
OBJECTIVE: To identify novel biomarker(s) for predicting advanced knee OA. METHODS: Study participants were derived from the Newfoundland Osteoarthritis Study and the Tasmania Older Adult Cohort Study. All knee OA cases were patients who underwent total knee replacement (TKR) due to primary OA. Metabolic profiling was performed on fasting plasma. Four thousand and eighteen plasma metabolite ratios that were highly correlated with that in SF in our previous study were generated as surrogates for joint metabolism. RESULTS: The discovery cohort included 64 TKR cases and 45 controls and the replication cohorts included a cross-sectional cohort of 72 TKR cases and 76 controls and a longitudinal cohort of 158 subjects, of whom 36 underwent TKR during the 10-year follow-up period. We confirmed the previously reported association of the branched chain amino acids to histidine ratio with advanced knee OA (P = 9.3 × 10(-7)) and identified a novel metabolic marker-the lysophosphatidylcholines (lysoPCs) to phosphatidylcholines (PCs) ratio-that was associated with advanced knee OA (P = 1.5 × 10(-7)) after adjustment for age, sex and BMI. When the subjects of the longitudinal cohort were categorized into two groups based on the optimal cut-off of the ratio of 0.09, we found the subjects with the ratio ⩾0.09 were 2.3 times more likely to undergo TKR than those with the ratio <0.09 during the 10-year follow-up (95% CI: 1.2, 4.3, P = 0.02). CONCLUSION: We identified the ratio of lysoPCs to PCs as a novel metabolic marker for predicting advanced knee OA. Further studies are required to examine whether this ratio can predict early OA change.