POS0129 ASSOCIATION BETWEEN OSTEOARTHRITIS-RELATED SERUM BIOCHEMICAL MARKERS OVER 11 YEARS AND KNEE MRI-BASED IMAGING BIOMARKERS IN MIDDLE-AGED ADULTS
Authors: B. Antony, A. Singh, L. Blizzard, A. Venn, G. Jones, J. Burgess, V. Parameswaran, F. Cicuttini, L. March, C. Ding
Journal: Annals of the Rheumatic Diseases (2021)

Background: Serum levels of osteoarthritis (OA)-related cartilage and joint-specific biochemical markers – cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3, and hyaluronan (HA) –are shown to be associated with cartilage degradation, joint tissue degradation, and synovitis in patients with OA. Although these OA-related biochemical markers may initially precede the MRI biomarkers of joint structural changes, such changes detected in MRI can lead to biochemical marker changes later as the condition progresses. However, there is a lack of data on OA-related biochemical markers’ association with MRI-based biomarkers in the middle-aged general population. Objectives: We aimed to describe the associations between OA-related biochemical markers and MRI-based imaging biomarkers in middle-aged adults followed up over 10-13 years. Methods: Blood samples were collected during the Childhood Determinants of Adult Health (CDAH)-1 study at baseline (year: 2004-06, age: 26–36 years) and 10-13 year follow-up (CDAH-3; year: 2014–2019, age: 36–49 years). Serum samples from baseline (n=156) and follow-up (n= 167) were analyzed for three OA-related biomarkers – namely COMP, MMP-3, and HA– using non isotopic ELISA assay methodology. Knee MRI scans were obtained during the CDAH-knee study (year: 2008-10, age: 30-40 years, n=313), and MRIs were assessed for cartilage volume, cartilage thickness, subchondral bone area, cartilage defects, and bone marrow lesions (BML). Univariable and multivariable (adjusted for age, sex, and body mass index (BMI)) linear regression and logistic regression were used to describe the association of biochemical marker at CDAH-1 and MRI-based imaging biomarkers at CDAH-knee, and Tobit regression was used to describe the association of MRI-based imaging biomarkers at CDAH-knee and biochemical markers at CDAH-3. Results: In the multivariable model for the association of biochemical marker with MRI-based imaging biomarkers (assessed after 4 years), we found a significant negative association of COMP with medial femorotibial compartment cartilage thickness (-0.010 (-0.019, -0.000) p=0.045), and MMP-3 with patellar cartilage thickness (-9.075 (-16.344, -1.807) p=0.015) and total bone area (-0.047 (-0.086, -0.007) p=0.020). No significant association was observed between HA and MRI markers. In the multivariable model for association of MRI-based imaging biomarkers with biochemical markers (assessed after 6-9 years), a significant negative association of total cartilage volume (-0.0005 (-0.0008, -0.0002) p=0.001) and total cartilage thickness (-0.628 (-1.143, -0.114) p=0.017) with MMP-3, and total bone area with COMP (0.270 (-0.474, -0.006) p=0.010) was observed. No significant association was observed between MRI-based imaging biomarkers and HA. Conclusion: COMP and MMP-3 levels were negatively associated with knee cartilage thickness assessed 4-years later. Similarly, knee cartilage thickness and volume were negatively associated with COMP and MMP-3 levels assessed 6-9 years later in population-based middle-aged adults, indicating an interdependent negative association of OA-related biochemical markers and MRI-based imaging biomarkers. These results suggest that OA-related biochemical markers may predict future MRI-based imaging biomarkers in middle-aged adults and thus represent possible at-risk populations to target for structure modification interventions. Acknowledgements: This project was funded by the National Health and Medical Research Council of Australia Project Grant and Royal Hobart Hospital Research Foundation Project Grant. Disclosure of Interests: Benny Antony Grant/research support from: Investigator-Initiated Clinical Trial support from Nat Rem Ltd., Ambrish Singh: None declared, Leigh Blizzard: None declared, Alison Venn: None declared, Graeme Jones Speakers bureau: Speaker for various pharma, Grant/research support from: Investigator-Initiated Clinical Trial support, John Burgess: None declared, Venkat Parameswaran: None declared, Flavia Cicuttini: None declared, Lyn March: None declared, Changhai Ding: None declared