An Editorial in Arthritis Research & Therapy [1] pointed out recently that "The field of osteoarthritis (OA) study is desperately in need of biomarkers. A sound biomarker could alter radically OA prediction, OA management, trials of therapies and our understanding of disease pathogenesis."

In the present Focus Letter we will focus on these clinical needs and present a recent scientific report on the topic by DJ Hunter et a [2], where AnaMars COMP-test was used. The authors showed thatCOMP was the only one of the tested serum biomarkers that predicts MRI-verified progression in symptomatic knee osteoarthritis at 30 months follow up. In the same editorial as above, they referred to the study of Hunter et al, and stated that "COMP is foremost among hitherto investigated biomarkers and is most consistently shown to predict knee OA progression".

We will also present two papers [3,4] with more focus on the association of an increase in serum COMP and radiographic progression of knee OA. In both these studies it is rather obvious that an increase in COMP is associated with an increase in progression, whereas no change in COMP indicates non-progression. An important finding in the study of Sharif et al [4] was that OA is a cyclic disease and not linear. Therefore, it seems more logical to follow changes in COMP and not only use a baseline value of COMP to predict progression or not.

The aim of this study was to investigate if serum COMP levels change in the early stage of OA development in randomly selected patients (n = 38, age range = 35-54 years) with chronic knee pain (< 3 months), normal baseline radiographs and no knee trauma.

Serum COMP levels (in house assay) and radiographs were performed at baseline and after 3 years. Development of radiographic OA at 3 years was defined as joint space narrowing < 3.5 mm of tibiofemoral and < 5 mm in patellofemoral joints.

After 3 years 23 (60%) patients had developed a radiographic OA and all but one showed an increase in serum COMP levels. The mean level of serum COMP was significantly (p<0.001) higher after 3 years compared to baseline in the population that developed OA. There was no difference in baseline COMP values between patients who had developed radiographic OA and those who had not after 3 years.

Most of the patients in the group that did not develop OA showed a decrease or no change in serum COMP level. In conclusion the authors state that serum levels of COMP increase with early radiographic OA.

Petersson I, Boegård T, Svensson B, Heinegård D, Saxne T:

Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint.
Br J Rheum 1998, 37:46-50

In an earlier publication, the authors showed that the increase in serum COMP levels during a year was significantly higher in OA patients who showed progression during that year compared to non-progressive patients.

The aim of the present study was to evaluate the longitudinal measurements of COMP to disease outcome over a 5-year period. Serum COMP (AnaMar Medical) was measured every 6 months over five years in patients (mean age = 63.6 years, n=115) with persistent knee pain and radiographic evidence of tibiofemoral OA. Knee radiographs were obtained at baseline and after 2, 3 and 5 years. Progression was defined as a joint space reduction of ≥2 mm or total knee replacement (TKR). The mean level of the measurements over the five years (area under the curve) were significantly (p < 0.003) higher in patients who had progressed at the 5 year follow up. Baseline serum COMP was significantly (p < 0.036) higher (14.12 U/L) in patients who had progressed after 5 years compared to non-progressive patients (12.62 U/L).

When using 5 years as endpoint, a one unit higher level of COMP (mean of baseline and 6 months measurements) increased the probability of radiographic progression by 15% as shown in a logistic regression analysis. However, the authors clearly showed that in the progressive group there was early as well as late progression over the 5 year follow up. They did not take into consideration if this nonlinearity in progression would increase the prognostic power of high COMP in shorter follow up periods. In conclusion the authors point out that serum COMP concentration was increased during the period of clear radiographic progression and loss of cartilage.

Sharif M, Kirwan JR, Elson ChJ, Granell R, Clarke S:

Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix levels over five years.
Arthritis & Rheumatism 2004, 50:2479-2488