Objective: We evaluated C-reactive protein (C-RP), a quantitative marker of the acute phase response, as a potential biomarker of prevalent and incident osteoarthritis of the knee (OAK).
Methods: Serum C-reactive protein concentrations were characterized with ultrasensitive rate nephelometry in a population-based sample of 1025 women (318 African-American and 707 Caucasian) who are enrollees in a study of musculoskeletal conditions at the mid-life. Assignment of OAK was based on Kellgren-Lawrence (K-L) scores of 2 or more on radiographs. Prevalent OAK was based on the baseline (1996) score while the classification of incident OAK was based on a score of 2 or greater at the follow-up examination 2.5 years later amongst those with a baseline K-L scores of 0 or 1.
Results: At baseline, the prevalence of radiographic OAK was 12% in participants who were aged 27-53 years and 18% in the subgroup of women aged 40-53 years. The mean C-RP value was 2.31 mg/L, with values ranging from below detection (0.3 mg/L) to 47.4 mg/L. Higher C-RP concentrations were associated with both prevalent and incident OAK (P < 0.0001, and P < 0.0001, respectively). For each K-L score increase from 0 to 3, there was a significantly higher mean C-RP value. Compared to women without incident OAK, women who developed OAK in the 2.5-year follow-up had significantly higher baseline C-RP concentrations. Women with bilateral OAK had higher C-RP concentrations than women with unilateral OAK (6.65 mg/L +/- 0.56 vs 3.63 mg/L +/- 0.42, P < 0.007). BMI was highly correlated with C-RP (r = 0.58) and obesity was an effect modifier with respect to OAK and C-RP concentrations. When stratified according presence or absence of OAK and obesity (BMI > 30 kg/m2), mean C-RP values were: obesity and OAK, 6.3 +/- 0.4 mg/L; obesity but not OAK, 4.3 mg/L +/- 0.2; no obesity but OAK, 1.7 mg/L +/- 0.8; and neither obesity nor OAK, 1.3 mg/L +/- 0.2 mg/L. These stratum means were significantly different from each other, indicating a higher C-RP with OAK after accounting for obesity.
Conclusion: C-RP, as a measure of an acute phase response and inflammation, is highly associated with OAK; however, its high correlation with obesity limits its utility as an exclusive marker for OAK.