Objective: To investigate the associations of molecular markers of joint tissue turnover with clinical and radiological variables in patients with hip osteoarthritis (OA).
Methods: Patients of the ECHODIAH trial cohort (60% female; mean age 63 yrs, disease duration 5 yrs) fulfilling the American College of Rheumatology criteria for hip OA were studied. Pain was assessed using a 100 mm visual analog scale, and the presence of night pain and morning stiffness was observed as the index of joint inflammation. Joint space width (JSW) and subchondral bone sclerosis were assessed on hip radiographs. Ten markers were measured, 8 in serum: N-propeptides of collagen type I (PINP) and type III (PIIINP), cartilage oligomeric matrix protein (COMP), YKL-40, hyaluronan (HA), matrix metalloproteases (MMP1 and MMP3), and ultrasensitive C-reactive protein (CRP); and 2 in urine: C-terminal crosslinking telopeptides of collagen type I (CTX-I) and type II (CTX-II). Analyses of 376 patients with measurements of all the markers included principal component analyses to identify independent clusters of markers; followed by stepwise multivariate regressions to determine associations between markers, clinical variables, and radiographic signs of joint damage.
Results: Markers could be segregated into independent clusters: CTX-II, PINP, and CTX-I for cartilage degradation and bone turnover; COMP, PIIINP, and HA as potential markers of synovitis; and CRP and YKL-40, which are likely to indicate systemic inflammation; plus MMP1 and MMP3. After adjustment for age, sex, and body mass index, pain was significantly associated with CTX-II (p = 0.0095) and CRP (p = 0.046) and joint inflammation with COMP (p = 0.013). Radiographic signs of joint damage were associated with CTX-II (p = 0.001 for JSW; p = 0.007 for bone sclerosis).
Conclusion: This cross-sectional study of OA molecular markers in a large cohort may provide biological evidence of different pathophysiological processes involved in hip OA. Among the markers measured, CTX-II showed the most consistent association with the symptoms and joint damage of OA.