The general biological processes represented by the 18 chosen biomarkers (counting each analyte in each fluid as one biomarker) are listed in table 1 and include catabolic and anabolic processes of cartilage and bone. Several biomarkers were quantified in both serum and urine. Biomarkers analysed in serum alone were cartilage oligomeric matrix protein (COMP), hyaluronan (HA), C-propeptide of type II collagen, N-terminal propeptide of collagen IIA (PIIANP), chondroitin sulfate 846 epitope, the C-terminal crosslinked telopeptide of type I collagen (CTXI) and matrix metalloproteinase 3. Biomarkers analysed in serum and urine were Col2-3/4 C-terminal cleavage product of types I and II collagen (C1, 2C), Col2-3/4 C-terminal cleavage product of human type II collagen (C2C competitive assay in serum, C2C-HUSA sandwich assay in urine), nitrated epitope of the α-helical region of type II collagen (Coll2-1 NO2) and the crosslinked N-telopeptide of type I collagen (NTXI). Biomarkers analysed in urine alone were the C-terminal crosslinked telopeptide type II collagen (CTXII), and alpha and beta isomerised versions of the CTXI (CTXIα and CTXIβ).
All biomarker assays were performed by LabCorp Clinical Trials, a Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathologists (CAP) certified division within LabCorp, with the exception of urine Col2-1 NO2, which was measured by Artialis, a Good Laboratory Practice-certified facility. All assays were run blinded to the clinical information. The biochemical markers measured in this study, the kit manufacturers and catalogue numbers and reported lower limits of quantification are listed in table 1. All biomarker data are freely available on the OAI website (https://oai.epi-ucsf.org/datarelease/).