Skip to main content
Top
Published in: Rheumatology International 4/2013

01-04-2013 | Original Article

The value of cartilage biomarkers in progressive knee osteoarthritis: cross-sectional and 6-year follow-up study in middle-aged subjects

Authors: Jaanika Kumm, Ann Tamm, Mare Lintrop, Agu Tamm

Published in: Rheumatology International | Issue 4/2013

Login to get access

Abstract

To determine the possible diagnostic and prognostic value of cartilage biomarkers in early-stage progressive and nonprogressive knee osteoarthritis (OA) in a population-based cohort of middle-aged subjects with chronic knee pain. Design tibiofemoral (TF) and patellofemoral (PF) radiographs were graded in 128 subjects (mean age at baseline, 45 ± 6.2 years) in 2002, 2005, and 2008. Cartilage degradation was assessed by urinary C-telopeptide fragments of type II collagen (uCTx-II), synthesis by serum type II A procollagen N-terminal propeptide (sPIIANP), and articular tissue turnover in general by cartilage oligomeric matrix protein (sCOMP). Several diagnostic associations were found between all studied biomarkers and progressive osteophytosis. COMP and CTx-II had a predictive value for subsequent progressive osteophytosis in multiple knee compartments and in case of CTx-II—also for progressive JSN. Over the first 3 years (2002–2005), significant associations were observed between COMP and progressive osteophytosis, whereas 3 years later (2005–2008) between CTx-II and progressive JSN. Thus, the associations between cartilage markers (COMP, CTx-II) and progression of radiographic OA features—osteophytes and JSN—were different between 2002–2005 and 2005–2008. Logistic regression revealed that for every unit increase in COMP level, there was 33 % higher risk for TF osteophyte progression. During early-stage OA, the presence and progression of osteophytosis is accompanied by increased level of cartilage biomarkers. This is the first study to demonstrate biochemical differences over the course of knee OA, illustrating a phasic nonpersistent character of OA with periods of progression and stabilization.
Literature
1.
go back to reference Felson DT (2009) Developments in the clinical understanding of osteoarthritis. Arthritis Res Ther 11(1):203PubMedCrossRef Felson DT (2009) Developments in the clinical understanding of osteoarthritis. Arthritis Res Ther 11(1):203PubMedCrossRef
2.
go back to reference Brandt KD, Doherty M, Lohmander LS (2003) Introduction: the concept of osteoarthritis as failure of the diarthrodial joint. In: Brandt KD, Doherty M, Lohmander LS (eds) Osteoarthritis. Oxford University Press, New York, pp 69–71 Brandt KD, Doherty M, Lohmander LS (2003) Introduction: the concept of osteoarthritis as failure of the diarthrodial joint. In: Brandt KD, Doherty M, Lohmander LS (eds) Osteoarthritis. Oxford University Press, New York, pp 69–71
3.
4.
go back to reference Golightly YM, Marshall SW, Kraus VB, Renner JB, Villaveces A, Casteel C et al (2011) Biomarkers of incident radiographic knee osteoarthritis. Arthritis Rheum 63(8):2276–2283PubMedCrossRef Golightly YM, Marshall SW, Kraus VB, Renner JB, Villaveces A, Casteel C et al (2011) Biomarkers of incident radiographic knee osteoarthritis. Arthritis Rheum 63(8):2276–2283PubMedCrossRef
5.
go back to reference Kraus VB (2011) Osteoarthritis year 2010 in review: biochemical markers. Osteoarthritis Cartilage 19:346–353PubMedCrossRef Kraus VB (2011) Osteoarthritis year 2010 in review: biochemical markers. Osteoarthritis Cartilage 19:346–353PubMedCrossRef
6.
go back to reference Ornetti P, Brandt K, Hellio-Le Graverand M-P, Hochberg M, Hunter DJ, Kloppenburg M et al (2009) OARSI–OMERACT definition of relevant radiological progression in hip/knee osteoarthritis. Osteoarthritis Cartilage 17(7):856–863PubMedCrossRef Ornetti P, Brandt K, Hellio-Le Graverand M-P, Hochberg M, Hunter DJ, Kloppenburg M et al (2009) OARSI–OMERACT definition of relevant radiological progression in hip/knee osteoarthritis. Osteoarthritis Cartilage 17(7):856–863PubMedCrossRef
7.
go back to reference Eckstein F, Le Graverand MP, Charles HC, Hunter DJ, Kraus VB, Sunyer T et al (2011) Clinical, radiographic, molecular and MRI-based predictors of cartilage loss in knee osteoarthritis. Ann Rheum Dis 70(7):1223–1230PubMedCrossRef Eckstein F, Le Graverand MP, Charles HC, Hunter DJ, Kraus VB, Sunyer T et al (2011) Clinical, radiographic, molecular and MRI-based predictors of cartilage loss in knee osteoarthritis. Ann Rheum Dis 70(7):1223–1230PubMedCrossRef
8.
go back to reference Conaghan PG, Hunter DJ, Maillefert JF, Reichmann WM, Losina E (2011) Summary and recommendations of the OARSI FDA osteoarthritis assessment of structural change working group. Osteoarthritis Cartilage 19:606–610PubMedCrossRef Conaghan PG, Hunter DJ, Maillefert JF, Reichmann WM, Losina E (2011) Summary and recommendations of the OARSI FDA osteoarthritis assessment of structural change working group. Osteoarthritis Cartilage 19:606–610PubMedCrossRef
9.
go back to reference Spector TD, Hart DJ, Byrne J, Harris PA, Dacre JE, Doyle DV (1993) Definition of osteoarthritis of the knee for epidemiological studies. Ann Rheum Dis 52:790–794PubMedCrossRef Spector TD, Hart DJ, Byrne J, Harris PA, Dacre JE, Doyle DV (1993) Definition of osteoarthritis of the knee for epidemiological studies. Ann Rheum Dis 52:790–794PubMedCrossRef
10.
go back to reference Bettica P, Cline G, Hart DJ, Meyer J, Spector TD (2002) Evidence for increased bone resorption in patients with progressive knee osteoarthritis. Arthritis Rheum 46(12):3178–3184PubMedCrossRef Bettica P, Cline G, Hart DJ, Meyer J, Spector TD (2002) Evidence for increased bone resorption in patients with progressive knee osteoarthritis. Arthritis Rheum 46(12):3178–3184PubMedCrossRef
11.
go back to reference Ding C, Garnero P, Cicuttini F, Scott F, Cooley H, Jones G (2005) Knee cartilage defects: association with early radiographic osteoarthritis, decreased cartilage volume, increased joint surface area and type II collagen breakdown. Osteoarthritis Cartilage 13:198–205PubMedCrossRef Ding C, Garnero P, Cicuttini F, Scott F, Cooley H, Jones G (2005) Knee cartilage defects: association with early radiographic osteoarthritis, decreased cartilage volume, increased joint surface area and type II collagen breakdown. Osteoarthritis Cartilage 13:198–205PubMedCrossRef
12.
go back to reference Kumm J, Tamm AE, Lintrop M, Tamm AO (2011) The prevalence and progression of radiographic knee osteoarthritis over 6 years in a population-based cohort of middle-aged subjects. Rheum Int. doi:10.1007/s00296-011-2221-3 Kumm J, Tamm AE, Lintrop M, Tamm AO (2011) The prevalence and progression of radiographic knee osteoarthritis over 6 years in a population-based cohort of middle-aged subjects. Rheum Int. doi:10.​1007/​s00296-011-2221-3
13.
go back to reference Sharif M, Kirwan JR, Elson CJ, Granell R, Clarke S (2004) Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years. Arthritis Rheum 50:2479–2488PubMedCrossRef Sharif M, Kirwan JR, Elson CJ, Granell R, Clarke S (2004) Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years. Arthritis Rheum 50:2479–2488PubMedCrossRef
14.
go back to reference Sharif M, Kirwan J, Charni N, Sandell LJ, Whittles C, Garnero P (2007) A 5-yr longitudinal study of type IIA collagen synthesis and total type II collagen degradation in patients with knee osteoarthritis—associations with disease progression. Rheumatology 46:938–943PubMedCrossRef Sharif M, Kirwan J, Charni N, Sandell LJ, Whittles C, Garnero P (2007) A 5-yr longitudinal study of type IIA collagen synthesis and total type II collagen degradation in patients with knee osteoarthritis—associations with disease progression. Rheumatology 46:938–943PubMedCrossRef
15.
go back to reference van Spil WE, DeGroot J, Lems WF, Oostveen JC, Lafeber FP (2010) Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systemic review applying the consensus BIPED criteria. Osteoarthritis Cartilage 18:605–612PubMedCrossRef van Spil WE, DeGroot J, Lems WF, Oostveen JC, Lafeber FP (2010) Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systemic review applying the consensus BIPED criteria. Osteoarthritis Cartilage 18:605–612PubMedCrossRef
16.
go back to reference Sharif M, Saxne T, Shepstone L, Kirwan JR, Elson CJ, Heinegard D et al (1995) Relationship between serum cartilage oligomeric matrix protein levels and disease progression in osteoarthritis of the knee joint. Br J Rheumatol 34:306–310PubMedCrossRef Sharif M, Saxne T, Shepstone L, Kirwan JR, Elson CJ, Heinegard D et al (1995) Relationship between serum cartilage oligomeric matrix protein levels and disease progression in osteoarthritis of the knee joint. Br J Rheumatol 34:306–310PubMedCrossRef
17.
go back to reference Vilim V, Olejarova M, Machacek S, Gatterova J, Kraus VB, Pavelka K (2002) Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis. Osteoarthritis Cartilage 10:707–713PubMedCrossRef Vilim V, Olejarova M, Machacek S, Gatterova J, Kraus VB, Pavelka K (2002) Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis. Osteoarthritis Cartilage 10:707–713PubMedCrossRef
18.
go back to reference Bruyere O, Collette J, Kothari M, Zaim S, White D, Genant H et al (2006) Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study. Ann Rheum Dis 65:1050–1054PubMedCrossRef Bruyere O, Collette J, Kothari M, Zaim S, White D, Genant H et al (2006) Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study. Ann Rheum Dis 65:1050–1054PubMedCrossRef
19.
go back to reference Hunter DJ, Li J, LaValley M, Bauer DC, Nevitt M, DeGroot J et al (2007) Cartilage markers and their association with cartilage loss on magnetic resonance imaging in knee osteoarthritis: the Boston Osteoarthritis Knee study. Arthritis Res Ther 9(5):R108PubMedCrossRef Hunter DJ, Li J, LaValley M, Bauer DC, Nevitt M, DeGroot J et al (2007) Cartilage markers and their association with cartilage loss on magnetic resonance imaging in knee osteoarthritis: the Boston Osteoarthritis Knee study. Arthritis Res Ther 9(5):R108PubMedCrossRef
20.
go back to reference Sowers MF, Karvonen-Gutierrez CA, Yosef M, Jannausch M, Jiang Y, Garnero P et al (2009) Longitudinal changes of serum COMP and urinary CTX-II predict X-ray defined knee osteoarthritis severity and stiffness in women. Osteoarthritis Cartilage 17:1609–1614PubMedCrossRef Sowers MF, Karvonen-Gutierrez CA, Yosef M, Jannausch M, Jiang Y, Garnero P et al (2009) Longitudinal changes of serum COMP and urinary CTX-II predict X-ray defined knee osteoarthritis severity and stiffness in women. Osteoarthritis Cartilage 17:1609–1614PubMedCrossRef
21.
go back to reference Dam EB, Byrjalsen I, Karsdal MA, Qvist P, Christiansen C (2009) Increased urinary excretion of C-telopeptides of type II collagen (CTX-II) predicts cartilage loss over 21 months by MRI. Osteoarthritis Cartilage 17:384–389PubMedCrossRef Dam EB, Byrjalsen I, Karsdal MA, Qvist P, Christiansen C (2009) Increased urinary excretion of C-telopeptides of type II collagen (CTX-II) predicts cartilage loss over 21 months by MRI. Osteoarthritis Cartilage 17:384–389PubMedCrossRef
22.
go back to reference Garnero P, Ayral X, Rousseau J-C, Christgau S, Sandell LJ, Dougados M et al (2002) Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis. Arthritis Rheum 10:2613–2624CrossRef Garnero P, Ayral X, Rousseau J-C, Christgau S, Sandell LJ, Dougados M et al (2002) Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis. Arthritis Rheum 10:2613–2624CrossRef
23.
go back to reference Bruyere O, Collette J, Kothari M, Zaim S, White D, Genant H et al (2006) Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study. Ann Rheum Dis 65:1050–1054PubMedCrossRef Bruyere O, Collette J, Kothari M, Zaim S, White D, Genant H et al (2006) Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study. Ann Rheum Dis 65:1050–1054PubMedCrossRef
24.
go back to reference Cibere J, Zhang H, Garnero P, Poole AR, Lobanok T, Saxne T et al (2009) Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study. Arthritis Rheum 60:1372–1380PubMedCrossRef Cibere J, Zhang H, Garnero P, Poole AR, Lobanok T, Saxne T et al (2009) Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study. Arthritis Rheum 60:1372–1380PubMedCrossRef
25.
go back to reference Schouten JS, Van den Ouweland FA, Valkenburg HA, Lamberts SW (1993) Insulin-like growth factor-1: a prognostic factor of knee osteoarthritis. Br J Rheumatol 32:274–280PubMedCrossRef Schouten JS, Van den Ouweland FA, Valkenburg HA, Lamberts SW (1993) Insulin-like growth factor-1: a prognostic factor of knee osteoarthritis. Br J Rheumatol 32:274–280PubMedCrossRef
26.
go back to reference Petersson IF, Boegard T, Svensson B, Heinegard D, Saxne T (1998) Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint. Br J Rheumatol 37:46–50PubMedCrossRef Petersson IF, Boegard T, Svensson B, Heinegard D, Saxne T (1998) Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint. Br J Rheumatol 37:46–50PubMedCrossRef
27.
go back to reference Sugiyama S, Itokazu M, Suzuki Y, Shimizu K (2003) Procollagen II C propeptide level in the synovial fluid as a predictor of radiographic progression in early knee osteoarthritis. Ann Rheum Dis 62:27–32PubMedCrossRef Sugiyama S, Itokazu M, Suzuki Y, Shimizu K (2003) Procollagen II C propeptide level in the synovial fluid as a predictor of radiographic progression in early knee osteoarthritis. Ann Rheum Dis 62:27–32PubMedCrossRef
28.
go back to reference Tamm A, Lintrop M, Veske K, Hansen U, Tamm A (2008) Prevalence of patello- and tibiofemoral osteoarthritis in Elva, Southern Estonia. J Rheumatol 35:543–544PubMed Tamm A, Lintrop M, Veske K, Hansen U, Tamm A (2008) Prevalence of patello- and tibiofemoral osteoarthritis in Elva, Southern Estonia. J Rheumatol 35:543–544PubMed
29.
go back to reference Boegard T, Rudling O, Petersson IF, Sanfridsson J, Saxne T, Svensson B et al (1998) Joint-space width in the axial view of the patello-femoral joint. Definitions and comparison with MR imaging. Acta Radiol 39:24–31PubMed Boegard T, Rudling O, Petersson IF, Sanfridsson J, Saxne T, Svensson B et al (1998) Joint-space width in the axial view of the patello-femoral joint. Definitions and comparison with MR imaging. Acta Radiol 39:24–31PubMed
30.
go back to reference Nagaosa Y, Mateus M, Hassan B, Lanyon B, Doherty M (2000) Development of logically devised line drawing atlas for grading of knee osteoarthritis. Ann Rheum Dis 59:587–595PubMedCrossRef Nagaosa Y, Mateus M, Hassan B, Lanyon B, Doherty M (2000) Development of logically devised line drawing atlas for grading of knee osteoarthritis. Ann Rheum Dis 59:587–595PubMedCrossRef
31.
go back to reference Botha-Scheepers S, Watt I, Breedveld FC, Kloppenburg M (2005) Reading radiographs in pairs or in chronological order influences radiological progression in osteoarthritis. Rheumatology 44:1452–1455PubMedCrossRef Botha-Scheepers S, Watt I, Breedveld FC, Kloppenburg M (2005) Reading radiographs in pairs or in chronological order influences radiological progression in osteoarthritis. Rheumatology 44:1452–1455PubMedCrossRef
32.
go back to reference Hashimoto S, Creighton-Achermann L, Takahashi K, Amiel D, Coutts RD, Lotz M (2002) Development and regulation of osteophyte formation during experimental osteoarthritis. Osteoarthritis Cartilage 10:180–187PubMedCrossRef Hashimoto S, Creighton-Achermann L, Takahashi K, Amiel D, Coutts RD, Lotz M (2002) Development and regulation of osteophyte formation during experimental osteoarthritis. Osteoarthritis Cartilage 10:180–187PubMedCrossRef
33.
go back to reference Blaney Davidson EN, Vitters EL, van Beuningen HM, van de Loo FAJ, van den Berg WB, van der Kraan PM (2007) Resemblance of osteophytes in experimental osteoarthritis to transforming growth factor beta-induced osteophytes: limited role of bone morphogenetic protein in early osteoarthritic osteophyte formation. Arthritis Rheum 56:4065–4073PubMedCrossRef Blaney Davidson EN, Vitters EL, van Beuningen HM, van de Loo FAJ, van den Berg WB, van der Kraan PM (2007) Resemblance of osteophytes in experimental osteoarthritis to transforming growth factor beta-induced osteophytes: limited role of bone morphogenetic protein in early osteoarthritic osteophyte formation. Arthritis Rheum 56:4065–4073PubMedCrossRef
34.
go back to reference Gelse K, Söder S, Eger W, Diemtar T, Aigner T (2003) Osteophyte development—molecular characterization of differentiation stages. Osteoarthritis Cartilage 11:141–148PubMedCrossRef Gelse K, Söder S, Eger W, Diemtar T, Aigner T (2003) Osteophyte development—molecular characterization of differentiation stages. Osteoarthritis Cartilage 11:141–148PubMedCrossRef
35.
go back to reference Kumm J, Tamm AE, Veske K, Lintrop M, Tamm AO (2006) Associations between cartilage oligomeric matrix protein and several articular tissues in early knee joint osteoarthritis. Rheumatology 45:1308–1309PubMedCrossRef Kumm J, Tamm AE, Veske K, Lintrop M, Tamm AO (2006) Associations between cartilage oligomeric matrix protein and several articular tissues in early knee joint osteoarthritis. Rheumatology 45:1308–1309PubMedCrossRef
36.
go back to reference Kumm J, Tamm AE, Lintrop M, Tamm AO (2009) Associations between ultrasonographic findings and bone/cartilage biomarkers in patients with early-stage knee osteoarthritis. Calcif Tissue Int 85:514–522PubMedCrossRef Kumm J, Tamm AE, Lintrop M, Tamm AO (2009) Associations between ultrasonographic findings and bone/cartilage biomarkers in patients with early-stage knee osteoarthritis. Calcif Tissue Int 85:514–522PubMedCrossRef
37.
go back to reference Di Cesare PE, Fang C, Leslie MP, Tulli H, Perris R, Carlson CS (2000) Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts. J Orthop Res 18:713–720PubMedCrossRef Di Cesare PE, Fang C, Leslie MP, Tulli H, Perris R, Carlson CS (2000) Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts. J Orthop Res 18:713–720PubMedCrossRef
38.
go back to reference Boegard T, Rudling O, Petersson IF, Jonsson K (1998) Correlation between radiographically diagnosed osteophytes and magnetic resonance detected cartilage defects in the tibiofemoral joint. Ann Rheum Dis 57:401–407PubMedCrossRef Boegard T, Rudling O, Petersson IF, Jonsson K (1998) Correlation between radiographically diagnosed osteophytes and magnetic resonance detected cartilage defects in the tibiofemoral joint. Ann Rheum Dis 57:401–407PubMedCrossRef
Metadata
Title
The value of cartilage biomarkers in progressive knee osteoarthritis: cross-sectional and 6-year follow-up study in middle-aged subjects
Authors
Jaanika Kumm
Ann Tamm
Mare Lintrop
Agu Tamm
Publication date
01-04-2013
Publisher
Springer-Verlag
Published in
Rheumatology International / Issue 4/2013
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-012-2463-8

Other articles of this Issue 4/2013

Rheumatology International 4/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.