@article {Poole1864, author = {A. Robin Poole and Nhuan Ha and Suzanne Bourdon and Eric C. Sayre and Ali Guermazi and Jolanda Cibere}, title = {Ability of a Urine Assay of Type II Collagen Cleavage by Collagenases to Detect Early Onset and Progression of Articular Cartilage Degeneration: Results from a Population-based Cohort Study}, volume = {43}, number = {10}, pages = {1864--1870}, year = {2016}, doi = {10.3899/jrheum.150917}, publisher = {The Journal of Rheumatology}, abstract = {Objective. To evaluate the association of a sandwich assay for cartilage collagenase-mediated degradation, the C2C human urine sandwich assay (IB-C2C-HUSA), with early and late knee cartilage pathology and with progression of cartilage damage.Methods. A population-based cohort with knee pain, age 40{\textendash}79 years, was evaluated at baseline (n = 253) and after mean 3.3 years (n = 161). We evaluated the IB-C2C-HUSA and a related competitive inhibition assay (C2C). The C2C assay was applied to serum (sC2C) and urine (uC2C). Based on knee radiographs and magnetic resonance imaging (MRI), 3 subgroups [no cartilage pathology, preradiographic cartilage pathology, and radiographic osteoarthritis (ROA)] were evaluated cross-sectionally for association with biomarker levels. Longitudinally, we evaluated whether baseline assays predict subsequent progression of cartilage degeneration, defined by MRI cartilage loss.Results. Cross-sectionally, statistically significant differences were seen in the 3 subgroups for IB-C2C-HUSA (p \< 0.001), with the highest levels seen in ROA, and for sC2C (p = 0.023), while no differences were seen for uC2C (p = 0.501). Baseline IB-C2C-HUSA levels were higher in progressors vs nonprogressors (p = 0.003). In logistic regression analysis, only baseline IB-C2C-HUSA was associated with an increased risk of progression of cartilage damage (OR 1.78, 95\% CI 1.03{\textendash}3.09).Conclusion. The IB-C2C-HUSA degradation assay detects the generation of a pathology-related cartilage collagen peptide(s) that increase(s) with onset of degeneration of knee articular cartilage. The baseline values are associated with progression of cartilage degeneration over 3 subsequent years. This assay may have value in clinical OA trials. Further, it points to collagenase activity as a therapeutic target for controlling degeneration of articular cartilage.}, issn = {0315-162X}, URL = {https://www.jrheum.org/content/43/10/1864}, eprint = {https://www.jrheum.org/content/43/10/1864.full.pdf}, journal = {The Journal of Rheumatology} }