Longitudinal changes of serum COMP and urinary CTX-II predict X-ray defined knee osteoarthritis severity and stiffness in women.
OBJECTIVE
To ascertain the predictive role of longitudinally acquired biochemical measures of cartilage turnover in relation to X-ray defined knee osteoarthritis (OAK), knee pain and functioning.


METHODS
This is a feasibility study based on 72 enrollees of the Michigan site of Study of Women's Health Across the Nation (SWAN), a longitudinal, population-based cohort study with 11 annual visits to characterize health at the mid-life. At visits in 1996, 1998 and 2007, radiographs were evaluated for the presence of OAK [>or=2 on the Kellgren and Lawrence (K-L) scale]. Knee pain and stiffness were assessed by interview. Functioning was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Cartilage oligomeric matrix protein (COMP) and Type II collagen telopeptides (CTX-II) were assayed in serum and urine samples collected on alternate years from 1997 to 2006. We related trajectories of the cartilage biochemical markers from these five time points to OAK severity (no OAK, K-L score<2; mild OAK, K-L score=2; moderate/severe OAK, K-L score=3 or 4), pain, stiffness, or functioning, using longitudinal non-linear mixed modeling.


RESULTS
The 2007 prevalence of X-ray defined OAK was 50% in these 72 women. Upward trajectories of COMP (P=0.02) and CTX-II (P=0.006) were associated with increased OAK severity and body size. COMP trajectories were associated with pain and stiffness, but not functioning. CTX-II trajectories were associated with stiffness scores, but not knee pain or functioning scores.


CONCLUSIONS
Multiple, biennial measures of COMP or CTX-II taken over a 10-year period were predictive of subsequent OAK and knee stiffness.
Sowers
M F
MF
University of Michigan School of Public Health, Department of Epidemiology, Ann Arbor, MI 48109, USA. mfsowers@umich.edu
Karvonen-Gutierrez
C A
CA
Yosef
M
M
Jannausch
M
M
Jiang
Y
Y
Garnero
P
P
Jacobson
J
J
D015415:Biomarkers / Q000378:metabolism; D064236:Cartilage Oligomeric Matrix Protein; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism*; D008137:Longitudinal Studies; D064235:Matrilin Proteins; D008593:Menopause / Q000378:metabolism; D008824:Michigan; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000378:metabolism*; D011237:Predictive Value of Tests; D011859:Radiography
D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human