OBJECTIVE: To evaluate 10 biomarkers in magnetic resonance imaging (MRI)-determined, pre-radiographically defined osteoarthritis (pre-ROA) and radiographically defined OA (ROA) in a population-based cohort of subjects with symptomatic knee pain. METHODS: Two hundred one white subjects with knee pain, ages 40-79 years, were classified into OA subgroups according to MRI-based cartilage (MRC) scores (range 0-4) and Kellgren/Lawrence (K/L) grades of radiographic severity (range 0-4): no OA (MRC score 0, K/L grade<2), pre-ROA (MRC score>or=1, K/L grade<2), or ROA (MRC score>or=1, K/L grade>or=2). Urine and serum samples were assessed for levels of the following biomarkers: urinary biomarkers C-telopeptide of type II collagen (uCTX-II), type II and types I and II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N-telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression was performed to evaluate the association of OA subgroup with individual biomarker levels and biomarker ratios, adjusted for age, sex, and body mass index. RESULTS: The risk of ROA versus no OA increased with increasing levels of uCTX-II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35-7.21), uC2C (OR 2.13, 95% CI 1.04-4.37), and uC1,2C (OR 2.07, 95% CI 1.06-4.04), and was reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30-0.94). The risk of pre-ROA versus no OA increased with increasing levels of uC2C (OR 2.06, 95% CI 1.05-4.01) and uC1,2C (OR 2.06, 95% CI 1.12-3.77). The ratios of type II collagen degradation markers to collagen synthesis markers were better than individual biomarkers at differentiating the OA subgroups, e.g., the ratio of [uCTX-II][uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47 (95% CI 1.34-9.03) and a risk of pre-ROA versus no OA of 2.56 (95% CI 1.03-6.40). CONCLUSION: Different cartilage degradation markers are associated with pre-ROA than are associated with ROA, indicating that their use as diagnostic markers depends on the stage of OA. Biomarker ratios contrasting cartilage degradation with cartilage synthesis are better able to differentiate OA stages compared with levels of the individual markers.
OBJECTIVE: To evaluate 10 biomarkers in magnetic resonance imaging (MRI)-determined, pre-radiographically defined osteoarthritis (pre-ROA) and radiographically defined OA (ROA) in a population-based cohort of subjects with symptomatic knee pain. METHODS: Two hundred one white subjects with knee pain, ages 40-79 years, were classified into OA subgroups according to MRI-based cartilage (MRC) scores (range 0-4) and Kellgren/Lawrence (K/L) grades of radiographic severity (range 0-4): no OA (MRC score 0, K/L grade<2), pre-ROA (MRC score>or=1, K/L grade<2), or ROA (MRC score>or=1, K/L grade>or=2). Urine and serum samples were assessed for levels of the following biomarkers: urinary biomarkers C-telopeptide of type II collagen (uCTX-II), type II and types I and II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N-telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression was performed to evaluate the association of OA subgroup with individual biomarker levels and biomarker ratios, adjusted for age, sex, and body mass index. RESULTS: The risk of ROA versus no OA increased with increasing levels of uCTX-II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35-7.21), uC2C (OR 2.13, 95% CI 1.04-4.37), and uC1,2C (OR 2.07, 95% CI 1.06-4.04), and was reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30-0.94). The risk of pre-ROA versus no OA increased with increasing levels of uC2C (OR 2.06, 95% CI 1.05-4.01) and uC1,2C (OR 2.06, 95% CI 1.12-3.77). The ratios of type II collagen degradation markers to collagen synthesis markers were better than individual biomarkers at differentiating the OA subgroups, e.g., the ratio of [uCTX-II][uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47 (95% CI 1.34-9.03) and a risk of pre-ROA versus no OA of 2.56 (95% CI 1.03-6.40). CONCLUSION: Different cartilage degradation markers are associated with pre-ROA than are associated with ROA, indicating that their use as diagnostic markers depends on the stage of OA. Biomarker ratios contrasting cartilage degradation with cartilage synthesis are better able to differentiate OA stages compared with levels of the individual markers.
Authors: Manish Kothari; Ali Guermazi; Gabriele von Ingersleben; Yves Miaux; Martine Sieffert; Jon E Block; Randall Stevens; Charles G Peterfy Journal: Eur Radiol Date: 2004-05-19 Impact factor: 5.315
Authors: V Vilím; R Vytásek; M Olejárová; S Machácek; J Gatterová; B Procházka; V B Kraus; K Pavelka Journal: Osteoarthritis Cartilage Date: 2001-10 Impact factor: 6.576
Authors: M P Recht; J Kramer; S Marcelis; M N Pathria; D Trudell; P Haghighi; D J Sartoris; D Resnick Journal: Radiology Date: 1993-05 Impact factor: 11.105
Authors: Alan L Elliott; Virginia B Kraus; Gheorghe Luta; Thomas Stabler; Jordan B Renner; Janice Woodard; Anca D Dragomir; Charles G Helmick; Marc C Hochberg; Joanne M Jordan Journal: Arthritis Rheum Date: 2005-01
Authors: F Nelson; L Dahlberg; S Laverty; A Reiner; I Pidoux; M Ionescu; G L Fraser; E Brooks; M Tanzer; L C Rosenberg; P Dieppe; A Robin Poole Journal: J Clin Invest Date: 1998-12-15 Impact factor: 14.808
Authors: Amanda E Nelson; Sanjay Chaudhary; Virginia B Kraus; Fang Fang; Jiu-Chiuan Chen; Todd A Schwartz; Xiaoyan A Shi; Jordan B Renner; Thomas V Stabler; Charles G Helmick; Kathleen Caldwell; A Robin Poole; Joanne M Jordan Journal: Environ Res Date: 2011-08-12 Impact factor: 6.498
Authors: Brian G Pietrosimone; Adam S Lepley; Hayley M Ericksen; Amy Clements; David H Sohn; Phillip A Gribble Journal: J Athl Train Date: 2015-04-06 Impact factor: 2.860
Authors: Constance R Chu; Shikha Sheth; Jennifer C Erhart-Hledik; Bao Do; Matthew R Titchenal; Thomas P Andriacchi Journal: J Orthop Res Date: 2017-09-27 Impact factor: 3.494
Authors: Sarah Malek; Hsin-Yi Weng; Shannon A Martinson; Mark C Rochat; Romain Béraud; Christopher B Riley Journal: PLoS One Date: 2020-11-19 Impact factor: 3.240