The ratio of type II collagen breakdown to synthesis and its relationship with the progression of knee osteoarthritis.
OBJECTIVE
To examine whether the baseline ratio of a type II collagen breakdown marker to a synthesis marker, or the level of these markers individually, is associated with the likelihood of knee osteoarthritis (OA) progression between baseline and 18 months.


METHODS
Participants were recruited from community sources and had knee OA. Blood was drawn at baseline. Collagen synthesis was measured by commercial enzyme-linked immunosorbent assay (ELISA) assay that detects c-propeptide of type II procollagen (CPII). Serum markers of collagenase cleavage of cartilage type II collagen [C2C epitope (COL2-3/4Clong mono) and C1,2C epitope (COL2-3/4Cshort)] were also assayed. Knee radiographs (semi-flexed with fluoro confirmation) were obtained at baseline and 18 months. OA progression was examined using worsening of joint space grade and worsening of Kellgren/Lawrence grade. The relationship between baseline serum markers and subsequent progression was analyzed from logistic regression.


RESULTS
Baseline levels of these markers, considered individually, were not associated with a change in the odds of progression. Belonging to the low synthesis tertile was associated with a greater likelihood of progression, approaching significance (adjusted odds ratio [OR] 1.86, 95% confidence interval [CI] 0.96, 3.63). A greater C2C:CPII ratio and C1,2C:CPII ratio were each associated with an increase in the odds of joint space grade progression, which approached significance (e.g., adjusted OR of C2C:CPII ratio was 3.15, 95% CI 0.91, 10.85).


CONCLUSIONS
While the degradation markers individually, considered as continuous variables, did not predict OA progression, belonging to the lower synthesis marker tertile and greater degradation/synthesis marker ratios were associated with an elevation in the odds of progression albeit not achieving significance.
Cahue
S
S
Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Sharma
L
L
Dunlop
D
D
Ionescu
M
M
Song
J
J
Lobanok
T
T
King
L
L
Poole
A Robin
AR
D000368:Aged; D015415:Biomarkers / Q000032:analysis* / Q000097:blood; D024043:Collagen Type II / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood / Q000473:pathology*
D015415:Biomarkers; D024043:Collagen Type II