Cartilage and bone biomarkers in rheumatoid arthritis: prediction of 10-year radiographic progression.
OBJECTIVE
As current predictors of joint destruction have low specificity, serological biomarkers reflecting bone and cartilage destruction have been proposed as tools in assessing prognosis of rheumatoid arthritis (RA). We examined whether serum concentrations of a panel of biomarkers could predict radiographic progression in patients with RA.


METHODS
A cohort of 238 patients with RA was followed longitudinally for 10 years with collection of clinical data and serum samples. These analyses focus on the 136 patients with radiographs of the hands available at baseline and at 5 and/or 10 years. Radiographs were scored according to the van der Heijde-modified Sharp score (SHS). Baseline sera were analyzed for receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), human cartilage glycoprotein-39 (YKL-40), C2C, collagen cross-linked C-telopeptide (CTX-I), and cartilage oligomeric matrix protein (COMP). Multivariate linear and logistic regression analyses were used to identify predictors of radiographic progression.


RESULTS
Baseline CTX-I levels were higher in progressors [0.41 ng/ml (interquartile range 0.31-0.75)] than in nonprogressors [0.32 ng/ml (IQR 0.21-0.49)], and were independently associated with 10-year change in radiographic damage score [ss = 16.4 (IQR 5.7-27.1)]. We found no association between radiographic progression and baseline serum levels of RANKL, OPG, C2C, YKL-40, or COMP.


CONCLUSIONS
This longterm followup study of patients with RA indicates a relationship between elevated CTX-I levels in serum and subsequent joint destruction. This association was, however, weak, and our study does not support that serum CTX-I or any of the other tested biomarkers will serve as more useful prognostic markers than current predictors such as anti-cyclic citrullinated peptide, radiographic damage early in the disease course, and signs of inflammation.
Syversen
Silje W
SW
Department of Rheumatology, Diakonhjemmet Hospital, Box 23, Vinderen, N-0319 Oslo, Norway. s.w.syversen@medisin.uio.no
Goll
Guro L
GL
van der Heijde
Désirée
D
Landewé
Robert
R
Gaarder
Per Ivar
PI
Odegård
Sigrid
S
Haavardsholm
Espen A
EA
Kvien
Tore K
TK
D054392:Adipokines; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D001175:Arthrography / Q000379:methods; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D002356:Cartilage / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D064236:Cartilage Oligomeric Matrix Protein; D000071451:Chitinase-3-Like Protein 1; D015331:Cohort Studies; D024042:Collagen Type I / Q000032:analysis / Q000378:metabolism; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D037102:Lectins; D008137:Longitudinal Studies; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D053244:Osteoprotegerin / Q000032:analysis / Q000378:metabolism; D010455:Peptides / Q000032:analysis / Q000378:metabolism; D053245:RANK Ligand / Q000032:analysis / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors
D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D064236:Cartilage Oligomeric Matrix Protein; D000071451:Chitinase-3-Like Protein 1; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D037102:Lectins; D064235:Matrilin Proteins; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C577553:TSP5 protein, human; C052929:collagen type I trimeric cross-linked peptide