Association of baseline levels of markers of bone and cartilage degradation with long‐term progression of joint damage in patients with early rheumatoid arthritis

Abstract

Objective. The known risk factors for radiologic progression in rheumatoid arthritis (RA) are not optimally discriminative in patients with early disease who do not have evidence of radiologic damage. We sought to determine whether urinary C-terminal crosslinking telopeptide of type I (CTX-I) and type II (CTX-II) collagen (markers of bone and cartilage destruction, respectively) are associated with long-term radiologic progression in patients with early RA.Methods. This was a prospective study of 110 patients with early RA who were participating in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) clinical trial and followup study, a randomized controlled trial comparing the efficacy of oral pulse prednisolone, methotrexate, plus sulfasalazine with sulfasalazine alone. We investigated the relationship between baseline levels of urinary CTX-I and CTX-II and the mean annual progression of joint destruction over a median of 4 years, as measured by changes in the modified Sharp score (average of 2 independent readers).Results. In multivariate logistic regression analysis, baseline urinary CTX-I and CTX-II levels in the highest tertile were the strongest predictors of radiologic progression (Sharp score increase >2 units/year; odds ratio 7.9 and 11.2, respectively), independently of treatment group, erythrocyte sedimentation rate (ESR), Disease Activity Score in 28 joints, rheumatoid factor (RF), and baseline joint damage (Sharp score). The likelihood ratios for a positive test were 3.8 and 8.0 for CTX-I and CTX-II, respectively, which compared favorably with the likelihood ratios for the ESR (3.0), baseline joint damage (1.6), and RF (1.8). When patients were grouped according to the presence (Sharp score >4, n ‫؍‬ 49) and absence (Sharp score <4, n ‫؍‬ 61) of joint damage at baseline, CTX-I and CTX-II levels were predictive only in those without baseline joint damage (odds ratio 14.9 and 25.7, respectively).Conclusion. High baseline levels of urinary CTX-I and CTX-II independently predict an increased risk of radiologic progression over 4 years in patients with early RA, especially those without radiologic joint damage. Urinary CTX-I and CTX-II may be useful for identifying individual RA patients at high risk of progression very early in the disease, before erosions can be detected radiographically. Such patients may be in special need of treatments that inhibit bone and cartilage degradation.

Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers

“…This finding with regard to CTX-II is consistent with previous reports that levels are elevated in patients with destructive RA (32) and are predictive of radiographic progression (33,34). A relationship with radiographic change has not, however, been previously demonstrated for urinary Pyr, although it is known that Pyr levels are elevated in patients with RA (35)(36)(37).…”

A cross sectional study of bone and cartilage biomarkers: correlation with structural damage in rheumatoid arthritis

“…Garnero et al (2002) have proved that patients with high CTX II level had a higher progression of joint damage over one year, regardless of the baseline extent of joint destruction and clinical indexes of disease activity [25,26]. Baseline CTX II was increased more than two-fold and remained high after a year in patients with early RA compared to controls.…”

Relationship of Focal Erosions, Bone Mineral Density, and Parathyroid Hormone in Rheumatoid Arthritis

“…The relationship between focal bone erosions and bone metabolism has been examined in previous studies. An ancillary finding of the COBRA trial 29 was the observation that the bone resorption markers urinary pyridinoline and deoxypyridinoline were correlated with erosion scores. A significant positive correlation between hand BMD and erosions was reported in a number of studies, but this is to be expected from the proximity of the erosions to the region of BMD measurement 13,30,31 .…”