Objective. To examine the role of low-grade inflammation in the etiology and progression of early osteoarthritis (OA) of the knee.

Methods. We used a new, high-sensitivity, automated monoclonal antibody immunoassay for the classic acute-phase protein, C-reactive protein (CRP), in serum. Anteroposterior radiographs of the knee with weight bearing were obtained on 845 women (ages 44–67) on entry into a population-based study of OA in Chingford, North London. In those defined radiologically as “cases,” the knee radiographs were repeated after 4 years.

Results. Levels of CRP were higher in 105 women with knee OA defined radiologically as Kellgren-Lawrence grade 2+ (median 2.4 mg/liter, interquartile range [IQR] 1.0–5.1), compared with 740 women without OA (median 0.7 mg/liter, IQR 0.3–1.8) (P < 0.001). Median levels of CRP were higher in the 31 women whose disease progressed at least 1 Kellgren-Lawrence grade (median 2.6 mg/liter, IQR 1.9–4.6), compared with the 39 whose disease did not (median 1.3 mg/liter, IQR 0.6–2.4) (P = 0.006). The significance of these differences persisted after adjustment for age, weight, height, smoking, knee pain, or injury. Classifying disease by the presence of joint space narrowing or osteophytes alone produced similar results.

Conclusion. CRP levels are modestly but significantly increased in women with early knee OA, and higher levels predict those whose disease will progress over 4 years, suggesting that low-grade inflammation may be a significant aspect of early OA and may be amenable to therapeutic intervention and secondary prevention.