CHICAGO — Baseline plasma matrix metalloproteinase 3 levels predicted joint space narrowing over 16 months in patients with knee osteoarthritis, according to findings from a pilot study.
However, the predictive accuracy of MMP-3 declines somewhat between 16 months and 30 months, Steve A. Mazzuca, Ph.D., reported at the 2004 World Congress on Osteoarthritis.
MMP-3, which is produced by chondrocytes and synoviocytes, has been implicated in the degradation of articular cartilage in osteoarthritis (OA). Compared with healthy subjects, patients with knee OA have higher concentrations of MMP-3 in their synovial fluid and blood.
“We are unable to answer the question right now if MMP-3 is an adequate surrogate for joint space narrowing, but it does correlate in real time,” said Dr. Mazzuca, professor and senior scientist at Indiana University, Indianapolis.
The 30-month study, led by Stefan Lohmander, M.D., of Lund (Sweden) University, involved 120 obese women 45–64 years old with unilateral knee OA.
Study participants were selected from a larger randomized trial of doxycycline, a disease-modifying OA drug. An equal number of patients had progressive radiographic knee OA and stable disease.
During the follow-up period, mean joint space narrowing in the index knee was 0.97 mm among those with progressive disease. There was the slightest increase, 0.03 mm, in joint space width in those with stable disease.
After adjustment for age, baseline joint space width, and treatment, a regression analysis showed that patients with the highest MMP-3 concentrations at baseline (more than 11.85 ng/mL) were more than three times as likely to progress to joint space narrowing in both knees at 16 months than patients with the lowest MMP-3 concentrations (1.5 ng/mL to 6.42 ng/mL) at baseline (odds ratio 3.48).
The association was less striking at 30 months, although the risk of progression remained significantly higher among patients with the highest MMP-3 levels (OR 2.09), Dr. Mazzuca reported at the congress, sponsored by the Osteoarthritis Research Society International.
The study also evaluated whether plasma MMP-3 values could have served as a surrogate marker in the original doxycycline trial. Serial MMP-3 levels examined at two time intervals (0–16 months and 16–30 months) found that both mean and maximal MMP-3 levels were significantly related to joint space narrowing in patients treated with placebo. For the doxycycline group, there was not a significant association at the first time interval, and a reverse association at the second interval. Dr. Mazzuca concluded that serum MMP-3 correlates with concurrent joint space narrowing in knees not treated with doxycycline.