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To assess the relation between the urinary concentrations of type II collagen C-telopeptide (UCTX-II) and radiographic signs of osteoarthritis (ROA) in the GARP (Genetics, Arthrosis and Progression) study.UCTX-II levels were measured in GARP study participants, who are sibling pairs predominantly with symptomatic osteoarthritis at multiple sites. Kellgren and Lawrence scores were used to assess ROA in the knees, hips, hands, and vertebral facet joints, and spinal disc degeneration. A proportionate score was made for each joint location, based on the number of joints with ROA. The sum total ROA score represents a measure of cartilage abnormalities within each patient. By using linear mixed models the total ROA score and the joint site specific ROA scores were correlated with the UCTX-II level.In 302 subjects the mean (SD) and median (range) for UCTX-II were 265 (168) and 219 (1346) ng/mmol creatine, respectively. There was a significant association between the total ROA score and UCTX-II levels. Subsequent multivariate analysis showed that the joint site specific ROA score at all joint sites, except for spinal disc degeneration, contributed independently to this association.The total ROA score of GARP patients, representing cartilage abnormalities at the most prevalent ROA joint locations, showed an excellent correlation with UCTX-II levels. The specific ROA scores at the hip, hand, facet, and knee joints additively and independently explained this association. Even in patients with osteoarthritis at multiple sites, UCTX-II may be a sensitive quantitative marker of ROA.