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Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study.
Arthritis Rheum 2009; 60(5):1372-80AR

Abstract

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+Show Affiliations

University of British Columbia, and Arthritis Research Centre of Canada, Vancouver General Hospital, Vancouver, British Columbia, Canada. jcibere@arthritisresearch.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19404937

Citation

Cibere, Jolanda, et al. "Association of Biomarkers With Pre-radiographically Defined and Radiographically Defined Knee Osteoarthritis in a Population-based Study." Arthritis and Rheumatism, vol. 60, no. 5, 2009, pp. 1372-80.
Cibere J, Zhang H, Garnero P, et al. Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study. Arthritis Rheum. 2009;60(5):1372-80.
Cibere, J., Zhang, H., Garnero, P., Poole, A. R., Lobanok, T., Saxne, T., ... Esdaile, J. M. (2009). Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study. Arthritis and Rheumatism, 60(5), pp. 1372-80. doi:10.1002/art.24473.
Cibere J, et al. Association of Biomarkers With Pre-radiographically Defined and Radiographically Defined Knee Osteoarthritis in a Population-based Study. Arthritis Rheum. 2009;60(5):1372-80. PubMed PMID: 19404937.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study. AU - Cibere,Jolanda, AU - Zhang,Hongbin, AU - Garnero,Patrick, AU - Poole,A Robin, AU - Lobanok,Tatiana, AU - Saxne,Tore, AU - Kraus,Virginia B, AU - Way,Amanda, AU - Thorne,Anona, AU - Wong,Hubert, AU - Singer,Joel, AU - Kopec,Jacek, AU - Guermazi,Ali, AU - Peterfy,Charles, AU - Nicolaou,Savvakis, AU - Munk,Peter L, AU - Esdaile,John M, PY - 2009/5/1/entrez PY - 2009/5/1/pubmed PY - 2009/7/1/medline SP - 1372 EP - 80 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 60 IS - 5 N2 - 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/19404937/Association_of_biomarkers_with_pre_radiographically_defined_and_radiographically_defined_knee_osteoarthritis_in_a_population_based_study_ L2 - https://doi.org/10.1002/art.24473 DB - PRIME DP - Unbound Medicine ER -