Background Knee Osteoarthritis (OA) is a heterogeneous disease with variable clinical outcomes. Some patients do not have any symptoms or significant functional loss for many years after the onset of the disease whereas others can progress rapidly to advanced stage , making it highly clinical relevant to identify those who are at high risk of progressing rapidly so that targeted interventions at early stage of the disease can be implemented [2–4].
Objectives To identify novel biomarker(s) for predicting advanced knee OA.
Methods Study participants were derived from the NFOAS and the TASOAC studies. All knee OA cases were patients who underwent total knee replacement (TKR) due to primary OA. Metabolic profiling was performed on fasting plasma using a targeted metabolomics approach. 4,018 plasma metabolite ratios that were highly correlated with that in synovial fluid 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 previous 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 - lysoPCs to 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 cutoff of 0.09 of the ratio, 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).
Conclusions 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.
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Acknowledgement We thank all the study participants who made this study possible, and all the staff in the NFOAS study who helped us in the collection of samples.
Disclosure of Interest None declared
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