Background:Osteoarthritis (OA) is the most common form of arthritis, and its impact is increasing year by year due to an aging population and lack of effective treatments. One of the main structural pathological changes of OA is the loss of articular cartilage. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development.Objectives:Using a metabolomics approach, the current study aimed to identify serum metabolomic signatures for predicting the loss of knee cartilage volume over 10 years in a well-established community-based cohort - the Tasmania Older Adult Cohort (TASOAC).Methods:TASOAC is an on-going, prospective, population-based study of older adults who were randomly selected from the roll of electors in Southern Tasmania, Australia. Participants had a right knee magnetic resonance imaging (MRI) scan at baseline and a 10-year follow-up. Cartilage volume was measured in the medial, lateral, and patellar compartments and change in cartilage volume over 10 years was calculated as percentage change per year. Fasting serum samples collected at 2.6-year follow-up were metabolomically profiled using the TMIC Prime Metabolomics Profiling Assay which measures a total of 143 metabolites. 129 metabolite concentrations passed the quality control and the pairwise ratios of them as the proxies of enzymatic reaction were calculated. Linear regression models were used to test the association between each of the metabolite ratios and change in cartilage volume in each of the knee compartments with adjustment for age, sex, and body mass index (BMI). The significance was defined at a=3.0×10-6 to control multiple testing of 16,512 ratios with Bonferroni method.Results:A total of 344 participants (51% females) were included. The mean baseline age was 62.83±6.13 years and the mean BMI was 27.48±4.41 kg/m2. The average follow-up time was 10.84±0.66 years. Cartilage volume reduced by 1.34±0.72%, 1.06±0.58%, and 0.98±0.46% per year in the medial, lateral, and patellar compartments, respectively. Our data showed that an increased ratio of hexadecenoylcarnitine (C16:1) to tetradecanoylcarnitine (C14) was associated with a 0.12±0.02% per year reduction in patellar cartilage volume (p = 8.80×10-7). An increased ratio of hexadecenoylcarnitine (C16:1) to dodecanoylcarnitine (C12) was also associated with a 0.12±0.02% per year reduction in patellar cartilage volume (p = 2.66×10-6). While there were several metabolite ratios associated with cartilage volume loss in the medial and lateral compartments, none of them reached the predefined significance level.Conclusion:Our data suggested that alteration of fatty acid β-oxidation is involved in knee cartilage loss, especially in the patellar compartment, and the serum ratio of C16:1 to C14 and to C12 could be used to predict long-term patellar cartilage loss.Acknowledgements:We thank all the study participants who made the study possible. The original TASOAC study was supported by the National Health and Medical Research Council (NHMRC) and the current study was supported by the Canadian Institutes of Health Research (CIHR).Disclosure of Interests:None declared
Prospective Association Between Inflammatory Markers and Knee Cartilage Volume Loss and Pain Trajectory
