Cross-sectional association of 10 molecular markers of bone, cartilage, and synovium with disease activity and radiological joint damage in patients with hip osteoarthritis: the ECHODIAH cohort.
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).


CONCLUSIONS
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.
Garnero
Patrick
P
INSERM Unit 403 and Molecular Markers, Synarc, Lyon, France. patrick.garnero@synarc.com
Mazières
Bernard
B
Guéguen
Alice
A
Abbal
Michel
M
Berdah
Laurent
L
Lequesne
Michel
M
Nguyen
Minh
M
Salles
Jean-Pierre
JP
Vignon
Eric
E
Dougados
Maxime
M
D015415:Biomarkers / Q000378:metabolism*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006621:Hip Joint / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D025341:Principal Component Analysis; D011859:Radiography; D012044:Regression Analysis; D013583:Synovial Membrane / Q000378:metabolism*
D015415:Biomarkers