The value of serum cartilage oligomeric matrix protein (COMP) as a marker of disease progression was investigated in 81 hospital out-patients with clinical knee osteoarthritis (OA). Progressing patients were defined by a decrease of > or = 2 mm in joint space on X-ray or requiring knee surgery during the 5 yr of follow-up. Of the 57 patients for whom full data were available, 20 progressed and 37 did not progress. Serum COMP levels increased during the first year in those who progressed (mean 6.42 micrograms/ml) (S.D. 6.64) compared to those who did not progress [mean 0.07 microgram/ml (S.D. 4.99); P < 0.001]. Changes in COMP during the first year were related to baseline COMP (r = -0.672, P < 0.001) and weight-to-height ratio (r = 0.272, P = 0.47). After allowing for these variables, serum COMP increased during the first year in progressive patients by 5.04 micrograms/ml [95% confidence interval (CI): (2.61, 7.46)] more than in non-progressive patients. Discriminant analysis gave a sensitivity of 70% and specificity of 78% at a cut-off value of 3.17 micrograms/ml. Baseline serum COMP levels did not differ between the groups but were related to late phase scintigraphy scan abnormalities. These observations suggest that the changes in serum COMP may have prognostic significance and are consistent with a model of OA in which early signs of episodic clinical progression can be found in the cartilage as well as in subchondral bone.

The objective of this study was to assess whether macroscopically normal articular cartilage taken from joints containing focal osteoarthritic lesions is histologically similar to articular cartilage taken from macroscopically normal joints. Metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints were obtained from 10 horses following euthanasia. Gross articular cartilage damage was scored and the cartilage assigned to one of two groups: (1) macroscopically normal cartilage from normal joints (control) and (2) macroscopically normal cartilage from diseased joints in which there were focal osteoarthritic lesions. Chondrocytes expressing specific cytokines and cytokine receptors were identified by immunohistochemistry. The total number of chondrocytes, and percentage of chondrocytes positive for these cytokines and receptors, was recorded in the superficial, middle, and deep cartilage zones. There was a significant increase in the expression of interleukin-1beta in the superficial and middle zones and interleukin-18 receptor in the superficial zone in Group 2 compared with Group 1 control samples. A significant positive correlation also was found between the grade of osteoarthritis and the percentage of chondrocytes positive for interleukin-1beta in the superficial and middle zones, and for interleukin-18 and interleukin-18R in the superficial zone. There was a significant increase in histology score for glycosaminoglycan loss in Group 2 compared with that in Group 1. In joints with focal osteoarthritis lesions, all the articular cartilage, even if macroscopically apparently normal, may have microscopic changes associated with osteoarthritis.

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