Metabolomic Signatures of Alcohol Consumption and Risk of Knee Osteoarthritis

University Of Connecticut Sch Of Med/Dnt, Farmington CT

Investigators

Abstract

PROJECT SUMMARY / ABSTRACT Osteoarthritis (OA) is the most prevalent joint disease and a leading cause of chronic pain and disability, affecting approximately 32.5 million Americans. In the absence of disease-modifying therapy, there is an urgent need for effective, widely available approaches to aid in the prevention and management of this common condition. As an important lifestyle factor, alcohol use has been associated with over 60 acute and chronic health conditions controversially. Previous studies have examined the cross-sectional association of alcohol consumption with the prevalence of knee OA, but the evidence from well-designed cohort studies or randomized clinical trials remains limited. Recently, using the data from Osteoarthritis Initiative (OAI), a multi-center prospective cohort study of knee OA, we observed a prospective association between excessive alcohol intake and a higher risk of knee OA. However, self-report alcohol assessment methods may be subject to recall bias and measurement error. Inaccurate measurement of alcohol exposure may make it difficult to detect moderate associations with disease risk. Biomarkers of alcohol intake taking into account the bioavailability and metabolism may better represent long-term exposures. Recently, metabolomics, by measuring a large number of downstream components (metabolites), provides the most integrated profile of biological status reflecting environmental and genetic interactions, and therefore may more precisely define alcohol and dietary exposures and provide better estimates of disease risk in epidemiologic studies. To date, intervention studies have identified a variety of metabolites related to alcohol consumption, and 15 of them have been well-validated by multiple studies. However, no study has ever assessed the association between alcohol-related metabolites and the future risk of knee OA. Using the existing data from a well-defined case-cohort study including 603 participants (237 incident knee OA cases and 366 non-cases) in the OAI cohort, we propose to examine whether individual metabolites related to alcohol intake predict the subsequent incidence of radiographic and symptomatic knee OA. Additionally, we will derive a composite score to measure the metabolomic signature of overall alcohol consumption accounting for the relative importance of individual metabolites and examine the association with the knee OA risk. An external sample from the Multicenter Osteoarthritis Study (MOST) will be used to validate the findings. Then we will examine whether alcohol-related metabolites and the metabolomic score influence imaging markers of knee OA (e.g. cartilage damage, bone marrow lesion, effusion). Finally, we will examine whether imaging markers of knee OA mediate the associations of alcohol-related metabolites and the composite score with the risk of knee OA. Using advanced metabolomic techniques, this innovative study will examine whether alcohol consumption is a modifiable risk factor for knee OA and offer the potential to identify OA prevention strategies, therefore it will have large potential public health implications. In addition, this study will provide preliminary data for future R01 grants to examine the underlying biological pathways in a multi-omics study (such as genomics, metabolomics, proteomics, etc.).