Factor analysis of six biomarkers in a longitudinal study of knee osteoarthritis suggests that pathological proccess occur in different joint tissues

Background: Osteoarthritis (OA) of the knee is a heterogeneous, complex joint disorder of uncertain aetiology that causes pain and disability. It is the most common joint disease, affecting about 10% of the population over the age of 50 years. Consideration of the potential involvement of different joint tissues in the process of OA has led to the hypothesis that the progression of OA is not linear, but proceeds through phases of disease activity involving sequential tissues. In order to test this hypothesis, we recruited 135 patients with predominantly medial tibiofemoral OA to monitor the natural progression of the disease sequentially (every 6 months) over 5 years using clinical criteria, imaging (radiography, scintigraphy, and dual x-ray absorptiometry), and serum biomarkers. Objectives: The purpose of this study was to explore the inter-relationships between six biomarkers of joint tissue pathology in a prospective study of osteoarthritis (OA) of the knee, seeking combinations of biomarkers that vary together but form factors, which vary independently. Such a finding may indicate the existence of distinct pathological processes within the OA joint. Methods: 115 patients with knee OA were studied prospectively at baseline, 6, 12, 18, and 24 months. Serum biomarkers measured by standard techniques were: cartilage oligomeric matrix protein (COMP), keratan sulphate (KS), C-reactive protein (CRP), cartilage glycoprotein-39 (YKL-40), osteocalcin (OC) and c-telopeptide of type I collagen (CrossLap). Factors were considered to exist only when they explained at least as much variance in the data as one of the initial variables. Factor loadings (the correlations between individual biomarkers and the factors) from a principal components analysis at baseline and at 6 months were considered high if >0.6 and low if