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.
abstract: 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.
  
  
  
  A population-based cohort with knee pain, age 40-79 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.
  
  
  
  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 1.03-3.09).
  
  
  
  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.
authors.affiliation: From the Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University, Montreal, Quebec; R&D Diagnostics, IBEX Pharmaceuticals, Montreal, Quebec; Arthritis Research Canada, Richmond, British Columbia, Canada; Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.A.R. Poole, PhD, DSc, Professor Emeritus, Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University; N. Ha, PhD, Manager, R&D Diagnostics, IBEX Pharmaceuticals, currently affiliated with Beckman Coulter, Miami, Florida, USA; S. Bourdon, BSc, Manager, Assay Production, IBEX Pharmaceuticals; E.C. Sayre, PhD, Statistical Analyst, Arthritis Research Canada; A. Guermazi, MD, PhD, Professor, Department of Radiology, Boston University School of Medicine; J. Cibere, MD, PhD, Associate Professor, Department of Medicine, University of British Columbia, and Senior Scientist, Arthritis Research Canada.
authors.forename: A Robin
authors.initials: AR
authors.lastname: Poole
authors.affiliation: From the Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University, Montreal, Quebec; R&D Diagnostics, IBEX Pharmaceuticals, Montreal, Quebec; Arthritis Research Canada, Richmond, British Columbia, Canada; Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.A.R. Poole, PhD, DSc, Professor Emeritus, Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University; N. Ha, PhD, Manager, R&D Diagnostics, IBEX Pharmaceuticals, currently affiliated with Beckman Coulter, Miami, Florida, USA; S. Bourdon, BSc, Manager, Assay Production, IBEX Pharmaceuticals; E.C. Sayre, PhD, Statistical Analyst, Arthritis Research Canada; A. Guermazi, MD, PhD, Professor, Department of Radiology, Boston University School of Medicine; J. Cibere, MD, PhD, Associate Professor, Department of Medicine, University of British Columbia, and Senior Scientist, Arthritis Research Canada.
authors.forename: Nhuan
authors.initials: N
authors.lastname: Ha
authors.affiliation: From the Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University, Montreal, Quebec; R&D Diagnostics, IBEX Pharmaceuticals, Montreal, Quebec; Arthritis Research Canada, Richmond, British Columbia, Canada; Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.A.R. Poole, PhD, DSc, Professor Emeritus, Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University; N. Ha, PhD, Manager, R&D Diagnostics, IBEX Pharmaceuticals, currently affiliated with Beckman Coulter, Miami, Florida, USA; S. Bourdon, BSc, Manager, Assay Production, IBEX Pharmaceuticals; E.C. Sayre, PhD, Statistical Analyst, Arthritis Research Canada; A. Guermazi, MD, PhD, Professor, Department of Radiology, Boston University School of Medicine; J. Cibere, MD, PhD, Associate Professor, Department of Medicine, University of British Columbia, and Senior Scientist, Arthritis Research Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bourdon
authors.affiliation: From the Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University, Montreal, Quebec; R&D Diagnostics, IBEX Pharmaceuticals, Montreal, Quebec; Arthritis Research Canada, Richmond, British Columbia, Canada; Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.A.R. Poole, PhD, DSc, Professor Emeritus, Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University; N. Ha, PhD, Manager, R&D Diagnostics, IBEX Pharmaceuticals, currently affiliated with Beckman Coulter, Miami, Florida, USA; S. Bourdon, BSc, Manager, Assay Production, IBEX Pharmaceuticals; E.C. Sayre, PhD, Statistical Analyst, Arthritis Research Canada; A. Guermazi, MD, PhD, Professor, Department of Radiology, Boston University School of Medicine; J. Cibere, MD, PhD, Associate Professor, Department of Medicine, University of British Columbia, and Senior Scientist, Arthritis Research Canada.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Sayre
authors.affiliation: From the Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University, Montreal, Quebec; R&D Diagnostics, IBEX Pharmaceuticals, Montreal, Quebec; Arthritis Research Canada, Richmond, British Columbia, Canada; Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.A.R. Poole, PhD, DSc, Professor Emeritus, Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University; N. Ha, PhD, Manager, R&D Diagnostics, IBEX Pharmaceuticals, currently affiliated with Beckman Coulter, Miami, Florida, USA; S. Bourdon, BSc, Manager, Assay Production, IBEX Pharmaceuticals; E.C. Sayre, PhD, Statistical Analyst, Arthritis Research Canada; A. Guermazi, MD, PhD, Professor, Department of Radiology, Boston University School of Medicine; J. Cibere, MD, PhD, Associate Professor, Department of Medicine, University of British Columbia, and Senior Scientist, Arthritis Research Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Guermazi
authors.affiliation: From the Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University, Montreal, Quebec; R&D Diagnostics, IBEX Pharmaceuticals, Montreal, Quebec; Arthritis Research Canada, Richmond, British Columbia, Canada; Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.A.R. Poole, PhD, DSc, Professor Emeritus, Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University; N. Ha, PhD, Manager, R&D Diagnostics, IBEX Pharmaceuticals, currently affiliated with Beckman Coulter, Miami, Florida, USA; S. Bourdon, BSc, Manager, Assay Production, IBEX Pharmaceuticals; E.C. Sayre, PhD, Statistical Analyst, Arthritis Research Canada; A. Guermazi, MD, PhD, Professor, Department of Radiology, Boston University School of Medicine; J. Cibere, MD, PhD, Associate Professor, Department of Medicine, University of British Columbia, and Senior Scientist, Arthritis Research Canada. jcibere@arthritisresearch.ca.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Cibere
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000473:pathology*; D024043:Collagen Type II / Q000652:urine*; D017364:Collagenases / Q000652:urine*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000473:pathology* / Q000652:urine; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D017364:Collagenases
keywords: IMMUNOASSAY; OSTEOARTHRITIS; TYPE II COLLAGEN