Serum biochemical markers of joint metabolism and inflammation in relation to clinical symptoms and physical function in adults with symptomatic knee osteoarthritis

Purpose: To date, the majority of osteoarthritis (OA) biomarker research has examined associations between biomarker levels and radiographic parameters. While radiography provides information on the structural burden of disease, it is insensitive to small changes in cartilage metabolism and does not always correlate with the most significant clinical expression in OA, pain. The purpose of this study was to investigate the associations between joint metabolism and inflammation with pain and physical function in adults with painful knee OA. This is in support of qualifying burden of disease biomarkers with clinical variables to support the study, management, and understanding of disease pathology in OA. Methods: The study used baseline data from 54 adults with knee OA participating in a nutrition intervention study. The 100 mm visual analogue scale version of theWestern Ontario andMcMaster University Osteoarthritis Index (WOMAC) was used to assess pain, stiffness, and physical disability. A minimumWOMAC pain score of 125 was used as a cutoff for participant inclusion. Physical functionwas assessed with a 6minute walk test (:6MWT) and stair climb task (SCT). Serum concentrations of biomarkers included measures of cartilage degradation (cartilage oligomeric matrix protein [COMP]), cartilage synthesis (typeIIA collagen N-propeptide [PIIANP]), synovial metabolism (hyaluronic acid [HA]), cartilage degrading enzyme levels (matrix metalloproteinase 3 [MMP-3]), and inflammation (C-reactive protein [CRP]). COMP, PIIANP, HA, and MMP-3 were measured by enzyme-linked immunosorbent assay and CRP was measured by an immunoturbidimetric assay. Correlations between biomarkers and clinical variables were assessed using Spearman correlation coefficients. Results: Participants (38 females and 16 males) had a mean age of 60 11.9 years, BMI of 32.6 7.5 kg/m2, disease duration of 86.6 112.2 months, and WOMAC pain score of 193.4 94.04 mm. Higher serum MMP-3 levels were significantly associated with higher WOMAC pain scores (R 1⁄4 0.27, p 1⁄4 0.05), controlling for age and body mass index (BMI). Higher levels of serum HA were significantly associated with decreased walking distance in the :6MWT (R 1⁄4 -0.35, p 1⁄4 0.01) and longer time taken in the SCT (R 1⁄4 0.31, p 1⁄4 0.02), when controlling for age and BMI. Higher CRP levels were significantly associated with higher WOMAC physical disability score (R 1⁄4 0.34, p 1⁄4 0.01) and worse performance in the :6MWT (R1⁄4 -0.38, p1⁄4 0.005) and SCT (R1⁄4 0.44, p1⁄4 0.001) when age was controlled for, but these associations were not significant when BMI was controlled for. COMP and PIIANP were not significantly associated with any clinical variables analyzed. Conclusion: SerumMMP-3 levels were associated with pain and serum HA levels were associated with physical functioning in adults who suffer from mild to moderate pain and impaired physical functioning from knee OA. Previous studies have shown that HA and MMP-3 are related to structural knee parameters in OA. Therefore, results from this study demonstrate that serum HA and MMP-3 also have potential as qualified burden of disease biomarkers that are clinically meaningful. (Research supported by the Ontario Ministry of Agriculture, Food and Rural Affairs, project #200121).