POS0190 ASSOCIATION BETWEEN OSTEOARTHRITIS-RELATED SERUM BIOCHEMICAL MARKERS OVER 11 YEARS AND KNEE SYMPTOMS IN MIDDLE-AGED ADULTS
Authors: A. Singh, L. Blizzard, A. Venn, G. Jones, J. Burgess, V. Parameswaran, C. Ding, B. Antony
Journal: Annals of the Rheumatic Diseases (2021)

Background: Serum levels of cartilage and joint-specific biochemical markers such as cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3, and hyaluronan (HA) are associated with cartilage degradation, joint tissue degradation, and synovitis in patients with OA. Change in these biomarkers may precede the morphological and clinical manifestations of OA and therefore have been explored as predictive markers in OA. However, few studies have evaluated the association of OA-related biomarkers with knee symptoms in general population-based middle-aged adults Objectives: To describe the associations between OA-related biomarkers and knee symptoms 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 ELISA. Knee symptoms (pain, stiffness, and dysfunction) were assessed using the WOMAC scale during the CDAH-3 phase. Univariable and multivariable (adjusted for age, sex, and body mass index (BMI)) zero-inflated Poisson regression models with random effects were used to describe the above associations Results: The prevalence of knee pain was 46%. In the multivariable model, adjusted for age, sex, and BMI, there was a significant positive association between COMP (ɞ=1.156, 95%CI: 0.989,1.324; p=0.04), MMP-3 (ɞ=1.013, 95%CI: 1.001,1.025; p=0.02), and HA (ɞ=1.008, 95%CI: 1.002,1.015, p=0.01) with knee pain and WOMAC-total score (Table 1) in middle-aged adults. The increase in knee pain per ng/ml increase in COMP, MMP-3, and HA was 15.7%, 1.3%, and 0.8%, respectively. The overall mean biomarker levels decreased over 10-13 years; however, the mean WOMAC-total scores were higher in participants whose COMP and HA levels increased (COMP: 24 (27.31), HA: 14.20 (22.60)) compared to those in whom it decreased or remained stable (COMP: 9.84 (16.83), and HA: 8.28 (13.22)) during this period. There was a significant positive association between COMP (ɞ=1.026, 95%CI: 1.002,1.050, p=0.03) and MMP-3 (ɞ=1.020, 95%CI: 1.009,1.030, p&lt;0.01) measured at baseline and knee pain assessed after 10-13 year in the middle-aged adults (Table 1) Table 1. Cross-sectional and longitudinal association between WOMAC symptoms and OA-related biomarkers Variables Longitudinal Biomarker at CDAH-1, knee symptom at CDAH-3 Cross-sectional Biomarker at CDAH-3, knee symptom at CDAH-3 Adjusted. Coef. (95%CI) p-value Adjusted. Coef. (95%CI) p-value COMP (Predictor) WOMAC-total 1.047 (1.035, 1.060) 1.088 (1.017, 1.159) p&lt;0.01 p=0.01 Stiffness 1.019 (0.988, 1.051) 0.877 (0.708, 1.057) p=0.23 p=0.12 Dysfunction 1.045 (1.030, 1.061) 1.040 (0.949, 1.130) p&lt;0.01 p=0.38 MMP3 (Predictor) WOMAC-total 1.026 (1.020, 1.031) 1.017 (1.010, 1.023) p&lt;0.01 p&lt;0.01 Pain 1.020 (1.009, 1.030) 1.013 (1.001, 1.025) p&lt;0.01 p=0.03 Stiffness 1.020 (1.004, 1.035) 1.004 (.987, 1.021) p=0.01 p=0.66 Dysfunction 1.029 (1.022, 1.037) 1.019 (1.010, 1.026) p&lt;0.01 p&lt;0.01 HA (Predictor) WOMAC-total 0.995 (0.991, 0.999) 1.007 (1.003, 1.010) p=0.01 p&lt;0.01 Pain 0.999 (0.991, 1.006) 1.008 (1.002, 1.015) p=0.75 p=0.01 Stiffness 0.989 (0.980, 0.998) 0.997 (0.989, 1.007) p=0.03 p=0.65 Dysfunction 1.003 (0.998, 1.009) 1.015 (1.010, 1.020) p= 0.22 p&lt;0.01 Bold denotes statistically significant. Model adjusted for age, sex, and BMI Conclusion: OA-related biochemical markers such as COMP and MMP-3 were positively associated with knee pain in population-based middle-aged adults. These results suggest biochemical markers measured in middle-aged adults may be used as a marker of joint pain Acknowledgements: AS is supported by International Graduate Research Scholarship, University of Tasmania. Disclosure of Interests: Ambrish Singh Employee of: Has worked in the past for Abbott and Eli Lilly and Company, Leigh Blizzard: None declared, Alison Venn: None declared, Graeme Jones: None declared, John Burgess: None declared, Venkat Parameswaran: None declared, Changhai Ding: None declared, Benny Antony: None declared