PMID- 11817593
OWN - NLM
STAT- MEDLINE
DCOM- 20020219
LR  - 20151119
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 46
IP  - 1
DP  - 2002 Jan
TI  - Association of baseline levels of urinary glucosyl-galactosyl-pyridinoline and 
      type II collagen C-telopeptide with progression of joint destruction in patients 
      with early rheumatoid arthritis.
PG  - 21-30
AB  - OBJECTIVE: To evaluate whether measurements of urinary 
      glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and urinary C-terminal 
      crosslinking telopeptide of type II collagen (CTX-II), 2 new markers of 
      destruction of the synovium and cartilage collagen breakdown, respectively, are 
      associated with the progression of joint damage in patients with early rheumatoid 
      arthritis (RA), and to compare this association with that with serum matrix 
      metalloproteinase 3 (MMP-3), a proteinase expressed by synovial tissue and 
      chondrocytes, and that with serum C-reactive protein (CRP), an index of systemic 
      inflammation. METHODS: The prospective study cohort comprised 116 patients with 
      early RA who were part of a large, double-blind, randomized study comparing the 
      efficacy of etanercept and methotrexate. The relationship between baseline levels 
      of urinary Glc-Gal-PYD, urinary CTX-II, and serum MMP-3 and the progression of 
      joint destruction, as measured by changes in the modified Sharp score (average 
      findings of 2 independent readers) over 1 year, was investigated. RESULTS: Levels 
      of urinary Glc-Gal-PYD (+70%), urinary CTX-II (+104%), and serum MMP-3 (+219%) 
      were elevated compared with the levels in 76 healthy controls. The baseline 
      levels of Glc-Gal-PYD (r = 0.30), CTX-II (r = 0.25), and MMP-3 (r = 0.29) 
      correlated with the changes over 1 year in the total Sharp score (joint space 
      narrowing and bone erosion). Patients with baseline levels of Glc-Gal-PYD, 
      CTX-II, and MMP-3 that were higher than the mean + 2 SD in healthy controls had a 
      significantly greater progression of joint damage, with an increase in the total 
      Sharp score over 1 year that was from 3- to 8-fold higher than that in patients 
      with low baseline levels of these markers. Moreover, patients with these higher 
      levels of Glc-Gal-PYD, CTX-II, and MMP-3 had a higher risk of progression of the 
      disease (increase in total Sharp score > or =0.5 units) than did the other 
      patients (relative risks and 95% confidence intervals [95% CI] 3.3 [95% CI 
      1.5-7.4], 2.5 [95% CI 1.1-5.7], and 2.5 [95% CI 1.1-5.6], respectively). The 
      baseline serum level of CRP was not significantly associated with the progression 
      of joint damage. Adjustment of the levels of Glc-Gal-PYD, CTX-II, and MMP-3 
      according to radiologic damage at baseline did not alter their association with 
      progression. After adjustment for serum CRP, the relative risk slightly 
      decreased, but remained significant, for Glc-Gal-PYD (2.6 [95% CI 1.1-6.3]). 
      Patients with both increased levels of the molecular markers and radiologic 
      damage at baseline had a higher risk of progression of joint damage than did 
      those with either high molecular marker levels or radiologic damage. CONCLUSION: 
      High baseline levels of Glc-Gal-PYD, CTX-II, and MMP-3 are associated with 
      increased risk of progression of joint destruction over 1 year in early RA. The 
      association between baseline levels of urinary Glc-Gal-PYD and progression of 
      joint erosion was independent of the severity of radiologic damage and 
      inflammation at baseline. Combining the measurements of these molecular markers 
      with radiologic assessment of joint damage may be useful for identifying patients 
      with RA who are at high risk of rapid progression and for whom early aggressive 
      treatment would be beneficial.
FAU - Garnero, Patrick
AU  - Garnero P
AD  - Synarc and Inserm Research Unit, Lyon, France. patrick.garnero@synarc.com
FAU - Gineyts, Evelyne
AU  - Gineyts E
FAU - Christgau, Stephan
AU  - Christgau S
FAU - Finck, Barbara
AU  - Finck B
FAU - Delmas, Pierre D
AU  - Delmas PD
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Amino Acids)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Collagen Type II)
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Galactosides)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 87672-07-9 (galactosylpyridinoline)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - IY9XDZ35W2 (Glucose)
RN  - OP401G7OJC (Etanercept)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Adult
MH  - Amino Acids/*urine
MH  - Antirheumatic Agents/administration & dosage
MH  - Arthritis, Rheumatoid/drug therapy/*pathology/*urine
MH  - Biomarkers
MH  - C-Reactive Protein/metabolism
MH  - Collagen Type II/*urine
MH  - Cross-Linking Reagents/metabolism
MH  - Etanercept
MH  - Female
MH  - Galactosides/*urine
MH  - Glucose/*metabolism
MH  - Glycosuria
MH  - Humans
MH  - Immunoglobulin G/administration & dosage
MH  - Joints/metabolism/*pathology
MH  - Male
MH  - Matrix Metalloproteinase 3/blood
MH  - Methotrexate/administration & dosage
MH  - Middle Aged
MH  - Peptide Fragments/urine
MH  - Prospective Studies
MH  - Receptors, Tumor Necrosis Factor/administration & dosage
EDAT- 2002/01/31 10:00
MHDA- 2002/02/20 10:01
CRDT- 2002/01/31 10:00
PHST- 2002/01/31 10:00 [pubmed]
PHST- 2002/02/20 10:01 [medline]
PHST- 2002/01/31 10:00 [entrez]
AID - 10.1002/1529-0131(200201)46:1<21::AID-ART10061>3.0.CO;2-Q [doi]
PST - ppublish
SO  - Arthritis Rheum. 2002 Jan;46(1):21-30. doi: 
      10.1002/1529-0131(200201)46:1<21::AID-ART10061>3.0.CO;2-Q.