A cross sectional analysis of 5 different markers of collagen degradation in rheumatoid arthritis.
OBJECTIVE
To compare 5 different assays measuring collagen degradation in rheumatoid arthritis (RA).


METHODS
Daily serum samples and 3 consecutive 24 h urine samples were obtained from 25 patients with RA and 20 control subjects. Levels of pyridinoline (PYD), deoxypyridinoline (DPYD), n-telopeptide (NTx), CrossLaps (XL), and carboxy-terminal peptide of type I collagen (ICTP) were determined by ELISA or radioimmunoassay. PYD, DPYD, NTx, and XL were measured in urine and expressed as a ratio of the amount of crosslink to mmoles of creatinine (Cr). ICTP was determined in serum. The day-to-day variability of urinary collagen crosslink levels and serum ICTP was assessed over 3 day hospitalization.


RESULTS
Four of the 5 markers were significantly elevated in the RA cohort compared to controls: PYD (nmol)/Cr (median 33.8 vs 19.3; p = 0.0001), NTx (nmol)/Cr (median 22.5 vs 13.8; p = 0.01), XL (microg)/Cr (median 191.4 vs 126.1; p = 0.01), and ICTP (microg/l) (median 5.8 vs 3.7; p = 0.001). In the RA group, higher levels of the markers were associated with concomitant prednisone therapy. The levels of the 4 urine markers and of ICTP in serum exhibited little day-to-day variability.


CONCLUSIONS
Biochemical evidence of increased collagen degradation can be readily observed in RA using simple quantitative assays. These measures have minimal short term, day-to-day variability and hence may be useful to assess the effect of potentially disease modifying therapies.
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. stcla003@mc.duke.edu
E W
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St Clair
S A
SA
Moak
W E
WE
Wilkinson
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L
Sanders
T
T
Lang
R A
RA
Greenwald
D000596:Amino Acids / Q000652:urine; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D003094:Collagen / Q000097:blood* / Q000652:urine; D024042:Collagen Type I; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000652:urine; D010455:Peptides / Q000097:blood* / Q000652:urine; D011241:Prednisone / Q000627:therapeutic use
D000596:Amino Acids; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen; D011241:Prednisone