OBJECTIVE: To investigate the association between urinary concentrations of C-telopeptide fragments of type II collagen (CTX-II) and the prevalence and progression of radiographic osteoarthritis (OA) of the knee and hip. METHODS: The study population consisted of a sample of 1,235 men and women ages > or =55 years who were enrolled in the Rotterdam Study (a population-based cohort study) and who were followed up for a mean of 6.6 years. Prevalent radiographic OA was defined as a Kellgren/Lawrence score > or =2; progression of radiographic OA was defined as a decrease in joint space width. RESULTS: Subjects with a CTX-II level in the highest quartile had a 4.2-fold increased risk of having radiographic OA of the knee (95% confidence interval [95% CI] 2.5-7.0) and of the hip (95% CI 2.2-7.8) compared with subjects with a CTX-II level in the lowest quartile. We observed a substantially stronger association between CTX-II levels and radiographic OA for subjects with hip pain (odds ratio [OR] 20.4, 95% CI 2.3-185.2) than for those without hip pain (OR 3.0, 95% CI 1.5-6.0). Subjects with a CTX-II level in the highest quartile had a 6.0-fold increased risk for progression of radiographic OA at the knee (95% CI 1.2-30.8) and an 8.4-fold increased risk for progression of radiographic OA at the hip (95% CI 1.0-72.9). All of these associations were found to be independent of known risk factors for OA, such as age, sex, and body mass index. CONCLUSION: This study shows that CTX-II is associated with both the prevalence and the progression of radiographic OA at the knee and hip. Importantly, this association is independent of known clinical risk factors for OA and seems stronger in subjects with joint pain.