 |
|
|
 |
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*
PATRICK GARNERO, BERNARD MAZIÈRES, ALICE GUÉGUEN, MICHEL ABBAL, LAURENT BERDAH, MICHEL LEQUESNE, MINH NGUYEN, JEAN-PIERRE SALLES, ERIC VIGNON, and MAXIME DOUGADOS
ABSTRACT.
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. (J Rheumatol 2005;32:697-703) Key Indexing Terms:
MOLECULAR MARKERS
From INSERM Unit 403 and Molecular Markers, Synarc, Lyon; Université Paul Sabatier, Service de Rhumatologie and Laboratoire d'immunologie, CHU Rangueil, Toulouse; INSERM U 88/IFR69, Paris; Laboratoires NEGMA-LERADS, Toussus-le-Noble; Service de Rhumatologie, Hôpital Léopold Bellan, Paris; Université René Descartes, Service de Rhumatologie, Hôpital Cochin, Paris; Service de biochimie, Hôpital de la Grave, Toulouse; and Service de Rhumatologie, Centre Hospitalier Lyon-Sud, Pierre Bénite, France. Supported in part by a grant from NEGMA-LERADS Laboratories. P. Garnero, PhD, INSERM Unit 403 and Molecular Markers, Synarc, Lyon; B. Mazières, MD, Service de Rhumatologie, CHU Rangueil, Toulouse; A. Guéguen, MS, INSERM U 88/IFR69, Paris; M. Abbal, PhD, Laboratoire d'immunologie, CHU Rangueil, Toulouse; L. Berdah, MD, Laboratoires NEGMA-LERADS, Toussus-le-Noble; M. Lequesne, MD, Service de Rhumatologie, Hôpital Léopold Bellan, Paris; M. Nguyen, MD, Service de Rhumatologie, Hôpital Cochin, Paris; J-P. Salles, PhD, Service de biochimie, Hôpital de la Grave, Toulouse; E. Vignon, MD, Service de Rhumatologie, Centre Hospitalier Lyon-Sud, Pierre Bénite; M. Dougados, MD, Service de Rhumatologie, Hôpital Cochin, Paris. *ECHODIAH: Evaluation of the Chondromodulating Effect of Diacerein in Osteoarthritis of the Hip Address reprint requests to Dr. P. Garnero, Synarc, Le Buroparc, T4, 16 rue Montbrillant, 69003 Lyon, France. E-mail: patrick.garnero@synarc.com Submitted May 10, 2004; revision accepted October 29, 2004. |