Grant: Project Grant

While total knee replacement (TKR) is the most effective treatment for end-stage knee osteoarthritis (OA), up to 20% of patients still suffer joint pain after their TKR. Sustained knee pain affects all aspects of health-related quality of life and is associated with 2.6 times greater risk for death. Identifying risk factors associated with this sustained knee pain would guide the development of treatments and help target care for patients. In our preliminary studies, we found that surgical factors were less likely to be the main factors for sustained knee pain, however, clinical depression, having multi-site musculoskeletal pain, and younger age were associated with it. Furthermore, we performed a metabolomic analysis (a study of all the metabolites in the blood) and found that one metabolite and three metabolite ratios were strongly associated with sustained knee pain. Very recently, our genome-wide association study (GWAS) identified certain genes to be associated with sustained knee pain. We also found in a pilot study that certain gut bacteria species may play a role in sustained knee pain. Taken together, our data suggests that sustained knee pain is complex and needs a holistic research approach to determine its underlying causes. In this proposal, we will conduct an integrative analysis of multi-omics data including genome, metabolome, microbiome, and exposome in the well-established Newfoundland Osteoarthritis Study (NFOAS) to identify markers and interacting networks for sustained knee pain. The causal relationship between the identified markers and sustained knee pain will be examined by Mendelian randomization. The findings will be validated in an independent cohort - the Tasmania Older Adult Cohort (TASOAC). This study will provide a better understanding of the causes of sustained knee pain and targets for developing new treatments.