Value of biomarkers in osteoarthritis: current status and perspectives.

[en] Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.

Disciplines :

General & internal medicine

Author, co-author :

Lotz, M.

Martel-Pelletier, J.

Christiansen, C.

Brandi, M.-L.

Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé

Chapurlat, R.

Collette, Julien ; Université de Liège - ULiège

Cooper, C.

Giacovelli, G.

Kanis, J. A.

More authors (11 more)

Language :

English

Title :

Value of biomarkers in osteoarthritis: current status and perspectives.

Publication date :

2013

Journal title :

Annals of the Rheumatic Diseases

ISSN :

0003-4967

eISSN :

1468-2060

Publisher :

BMJ Group, London, United Kingdom

Volume :

Pages :

1756-1763

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 05 September 2013

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4 (4 by ULiège)

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Scopus citations^®

227

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194

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202

Bibliography

Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet 2011;377:2115-26.
Committee for Medicinal Products for Human Use. Guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis. 2010. http://www.ema.europa.eu (accessed 19 Sept 2012).
Food and Drug Administration. Guidance for industry. Clinical development programs for drugs, devices, and biological products intended for the treatment of osteoarthritis. 2011. http://www.fda.gov (accessed 12 Jun 2012).
Hunter DJ, Guermazi A. Imaging techniques in osteoarthritis. PM&R 2012;4: S68-74.
Atkinson AJ, Colburn WA, DeGruttola VG, et al. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69:89-95.
Iagnocco A, Perricone C, Scirocco C, et al. The interobserver reliability of ultrasound in knee osteoarthritis. Rheumatology (Oxford) 2012;51:2013-19.
Eckstein F, Wirth W. Quantitative cartilage imaging in knee osteoarthritis. Arthritis 2011;2011:475684.
Pelletier JP, Cooper C, Peterfy C, et al. What is the predictive value of MRI for the occurrence of knee replacement surgery in knee osteoarthritis? Ann Rheum Dies 2013;72:1594-604.
Scanzello CR, Plaas A, Crow MK. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound? Cur Open Rheumatic 2008;20:565-72.
Kraus VB, Burnett B, Coindreau J, et al. Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis. Osteoarthritis Cartilage 2011;19:515-42.
Rousseau JC, Garnero P. OARSI Primer. Chapter 10. Biochemical markers. 2010. http://primer.oarsi.org (accessed 6 Nov 2012).
Charni-Ben TN, Garnero P. Monitoring cartilage turnover. Cur Rheumatic Rep 2007;9:16-24.
Mobasheri A. Osteoarthritis year 2012 in review: biomarkers. Osteoarthritis Cartilage 2012;20:1451-64.
Rousseau JC, Garnero P. Biological markers in osteoarthritis. Bone 2012;51:265-77.
Williams FM, Spector TD. Biomarkers in osteoarthritis. Arthritis Res Ther 2008;10:101.
Rousseau JC, Delmas PD. Biological markers in osteoarthritis. Nat Clin Pract Rheumatic 2007;3:346-56.
Karsdal MA, Madsen SH, Christiansen C, et al. Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity. Arthritis Res Ther 2008;10:R63.
Karsdal MA, Nielsen MJ, Sand JM, et al. Extracellular matrix remodeling: the common denominator in connective tissue diseases possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure. Assay Drug Dev Technol 2013;11:70-92.
Karsdal MA, Woodworth T, Henriksen K, et al. Biochemical markers of ongoing joint damage in rheumatoid arthritis-current and future applications, limitations and opportunities. Arthritis Res Ther 2011;13:215.
van Spil WE, Degroot J, Lems WF, et al. Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria. Osteoarthritis Cartilage 2010;18:605-12.
Bauer DC, Hunter DJ, Abramson SB, et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthritis Cartilage 2006;14:723-7.
Kraus VB. Osteoarthritis year 2010 in review: biochemical markers. Osteoarthritis Cartilage 2011;19:346-53.
Kraus VB, Nevitt M, Sandell LJ. Summary of the OA biomarkers workshop 2009-biochemical biomarkers: biology, validation, and clinical studies. Osteoarthritis Cartilage 2010;18:742-5.
Jain KK. The handbook of biomarkers. New York, NY: Springer, 2010.
Garnero P, Piperno M, Gineyts E, et al. Cross sectional evaluation of biochemical markers of bone, cartilage, and synovial tissue metabolism in patients with knee osteoarthritis: relations with disease activity and joint damage. Ann Rheum Dies 2001;60:619-26.
Dam EB, Loog M, Christiansen C, et al. Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers. Arthritis Res Ther 2009;11: R115.
King KB, Lindsey CT, Dunn TC, et al. A study of the relationship between molecular biomarkers of joint degeneration and the magnetic resonance-measured characteristics of cartilage in 16 symptomatic knees. Magn Reson Imaging 2004;22:1117-23.
Wang Y, Li D, Xu N, et al. Follistatin-like protein 1: a serum biochemical marker reflecting the severity of joint damage in patients with osteoarthritis. Arthritis Res Ther 2011;13:R193.
Rousseau JC, Zhu Y, Miossec P, et al. Serum levels of type IIA procollagen amino terminal propeptide (PIIANP) are decreased in patients with knee osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage 2004;12:440-7.
Dufield DR, Nemirovskiy OV, Jennings MG, et al. An immunoaffinity liquid chromatography-tandem mass spectrometry assay for detection of endogenous aggrecan fragments in biological fluids: use as a biomarker for aggrecanase activity and cartilage degradation. Anal Biochem 2010;406:113-23.
Chayanupatkul M, Honsawek S. Soluble receptor for advanced glycation end products (sRAGE) in plasma and synovial fluid is inversely associated with disease severity of knee osteoarthritis. Clin Biochem 2010;43:1133-7.
Huang K, Wu LD. YKL-40: a potential biomarker for osteoarthritis. J Int Med Res 2009;37:18-24.
Johansen JS, Hvolris J, Hansen M, et al. Serum YKL-40 levels in healthy children and adults. Comparison with serum and synovial fluid levels of YKL-40 in patients with osteoarthritis or trauma of the knee joint. Br J Rheumatic 1996;35:553-9.
Wang Q, Rozelle AL, Lepus CM, et al. Identification of a central role for complement in osteoarthritis. Nat Med 2011;17:1674-9.
Meulenbelt I, Kloppenburg M, Kroon HM, et al. Urinary CTX-II levels are associated with radiographic subtypes of osteoarthritis in hip, knee, hand, and facet joints in subject with familial osteoarthritis at multiple sites: the GARP study. Ann Rheum Dies 2006;65:360-5.
Kraus VB, Kepler TB, Stabler T, et al. First qualification study of serum biomarkers as indicators of total body burden of osteoarthritis. PLoS ONE 2010;5:e9739.
Huebner JL, Bay-Jensen AC, Leeming DJ, et al. Urinary markers, alpha CTX and CTXII, are indicative of OA severity and bone turnover. Oral communication 048. Osteoarthritis Cartilage 2010;18(Suppl 2):S29-30.
Larsson S, Englund M, Struglics A, et al. The association between changes in synovial fluid levels of ARGS-aggrecan fragments, progression of radiographic osteoarthritis and self-reported outcomes: a cohort study. Osteoarthritis Cartilage 2012;20:388-95.
Clark AG, Jordan JM, Vilim V, et al. Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project. Arthritis Rheum 1999;42:2356-64.
Wislowska M, Jablonska B. Serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and knee osteoarthritis. Clin Rheumatic 2005;24:278-84.
Denoble AE, Huffman KM, Stabler TV, et al. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc Natl Acad Sci USA 2011;108:2088-93.
Catterall JB, Hsueh MF, Stabler TV, et al. Protein modification by deamidation indicates variations in joint extracellular matrix turnover. J Biol Chem 2012;287:4640-51.
Meulenbelt I, Kloppenburg M, Kroon HM, et al. Clusters of biochemical markers are associated with radiographic subtypes of osteoarthritis (OA) in subject with familial OA at multiple sites. The GARP study. Osteoarthritis Cartilage 2007;15:379-85.
Chen HC, Kraus VB, Li YJ, et al. Genome-wide linkage analysis of quantitative biomarker traits of osteoarthritis in a large, multigenerational extended family. Arthritis Rheum 2010;62:781-90.
Lago R, Gomez R, Otero M, et al. A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes. Osteoarthritis Cartilage 2008;16:1101-9.
Lago F, Dieguez C, Gomez-Reino J, et al. The emerging role of adipokines as mediators of inflammation and immune responses. Cytokine Growth Factor Rev 2007;18:313-25.
Berner HS, Lyngstadaas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone-forming cells. Bone 2004;35:842-9.
Gosset M, Berenbaum F, Salvat C, et al. Crucial role of visfatin/pre-B cell colonyenhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: possible influence on osteoarthritis. Arthritis Rheum 2008;58:1399-409.
Vuolteenaho K, Koskinen A, Kukkonen M, et al. Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage-mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production. Mediators Inflamm 2009;2009:345838.
Ku JH, Lee CK, Joo BS, et al. Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis. Clin Rheumatic 2009;28:1431-5.
Schaffler A, Ehling A, Neumann E, et al. Adipocytokines in synovial fluid. JAMA 2003;290:1709-10.
Reijman M, Hazes JM, Bierma-Zeinstra SM, et al. A new marker for osteoarthritis: cross-sectional and longitudinal approach. Arthritis Rheum 2004;50:2471-8.
Dam EB, Byrjalsen I, Karsdal MA, et al. Increased urinary excretion of C-telopeptides of type II collagen (CTX-II) predicts cartilage loss over 21 months by MRI. Osteoarthritis Cartilage 2009;17:384-9.
van Spil WE, Drossaers-Bakker KW, Lafeber FP. Associations of CTX-II with biochemical markers of bone turnover raise questions on its tissue origin: data from CHECK, a cohort study of early osteoarthritis. Ann Rheum Dies 2013;72:29-36.
Sowers MF, Karvonen-Gutierrez CA, Yosef M, et al. Longitudinal changes of serum COMP and urinary CTX-II predict X-ray defined knee osteoarthritis severity and stiffness in women. Osteoarthritis Cartilage 2009;17:1609-14.
Golightly YM, Marshall SW, Kraus VB, et al. Biomarkers of incident radiographic knee osteoarthritis: do they vary by chronic knee symptoms? Arthritis Rheum 2011;63:2276-83.
Pelletier JP, Raynauld JP, Caron J, et al. Decrease in serum level of matrix metalloproteinases is predictive of the disease-modifying effect of osteoarthritis drugs assessed by quantitative MRI in patients with knee osteoarthritis. Ann Rheum Dies 2010;69:2095-101.
Berry PA, Maciewicz RA, Wluka AE, et al. Relationship of serum markers of cartilage metabolism to imaging and clinical outcome measures of knee joint structure. Ann Rheum Dies 2010;69:1816-22.
Bay-Jensen AC, Liu Q, Byrjalsen I, et al. Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM-increased serum CIIM in subjects with severe radiographic osteoarthritis. Clin Biochem 2011;44:423-9.
Ishijima M, Watari T, Naito K, et al. Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis. Arthritis Res Ther 2011;13:R22.
Chen WP, Bao JP, Feng J, et al. Increased serum concentrations of visfatin and its production by different joint tissues in patients with osteoarthritis. Clin Chem Lab Med 2010;48:1141-5.
Laurberg TB, Frystyk J, Ellingsen T, et al. Plasma adiponectin in patients with active, early, and chronic rheumatoid arthritis who are steroid-and disease-modifying antirheumatic drug-naive compared with patients with osteoarthritis and controls. J Rheumatic 2009;36:1885-91.
Yusuf E, Ioan-Facsinay A, Bijsterbosch J, et al. Association between leptin, adiponectin and resistin and long-term progression of hand osteoarthritis. Ann Rheum Dies 2011;70:1282-4.
Berry PA, Jones SW, Cicuttini FM, et al. Temporal relationship between serum adipokines, biomarkers of bone and cartilage turnover, and cartilage volume loss in a population with clinical knee osteoarthritis. Arthritis Rheum 2011;63:700-7.
Stannus OP, Jones G, Quinn SJ, et al. The association between leptin, interleukin-6, and hip radiographic osteoarthritis in older people: a cross-sectional study. Arthritis Res Ther 2010;12:R95.
Smith JW, Martins TB, Gopez E, et al. Significance of C-reactive protein in osteoarthritis and total knee arthroplasty outcomes. Ther Adv Musculoskelet Dies 2012;4:315-25.
Sharif M, Shepstone L, Elson CJ, et al. Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee. Ann Rheum Dies 2000;59:71-4.
Stannus O, Jones G, Cicuttini F, et al. Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthritis Cartilage 2010;18:1441-7.
Reginster J-Y, Badurski J, Bellamy N, et al. Efficacy and safety of oral strontium ranelate for the treatment of knee osteoarthritis: results of a randomised double-blind, placebo-controlled trial. Ann Rheum Dies 2013;72:179-86.
Meulenbelt I, Kraus VB, Sandell LJ, et al. Summary of the OA biomarkers workshop 2. Osteoarthritis Cartilage 2011;19:1091-4.
Valdes AM, Loughlin J, Oene MV, et al. Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee. Arthritis Rheum 2007;56:137-46.
Zeggini E, Panoutsopoulou K, Southam L, et al. Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study. Lancet 2012;380:815-23.
Zhai G, Wang-Sattler R, Hart DJ, et al. Serum branched-chain amino acid to histidine ratio: a novel metabolomic biomarker of knee osteoarthritis. Ann Rheum Dies 2010;69:1227-31.
Adams SB Jr, Setton LA, Kensicki E, et al. Global metabolic profiling of human osteoarthritic synovium. Osteoarthritis Cartilage 2012;20:64-7.
Suhre K, Shin SY, Petersen AK, et al. Human metabolic individuality in biomedical and pharmaceutical research. Nature 2011;477:54-60.
de Seny D, Sharif M, Fillet M, et al. Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis. Ann Rheum Dies 2011;70: 1144-52.
Onnerfjord P, Khabut A, Reinholt FP, et al. Quantitative proteomic analysis of eight cartilaginous tissues reveals characteristic differences as well as similarities between subgroups. J Biol Chem 2012;287:18913-24.
Castro-Perez JM, Kamphorst J, Degroot J, et al. Comprehensive LC-MS E lipidomic analysis using a shotgun approach and its application to biomarker detection and identification in osteoarthritis patients. J Proteome Res 2010;9:2377-89.
Gobezie R, Kho A, Krastins B, et al. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res Ther 2007;9:R36.
Ritter SY, Subbaiah R, Bebek G, et al. Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues. Arthritis Rheum 2013;65:981-92.
Hunter DJ, Nevitt M, Losina E, et al. Biomarkers for osteoarthritis: current position and steps towards further validation. Rheum Dies Clin North Am 2013 In press.
Charni-Ben TN, Desmarais S, Bay-Jensen AC, et al. The type II collagen fragments Helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation. Osteoarthritis Cartilage 2008;16:1183-91.
Manno RL, Bingham CO III, Paternotte S, et al. OARSI-OMERACT initiative: defining thresholds for symptomatic severity and structural changes in disease modifying osteoarthritis drug (DMOAD) clinical trials. Osteoarthritis Cartilage 2012;20:93-101.
van Spil WE, Jansen NW, Bijlsma JW, et al. Clusters within a wide spectrum of biochemical markers for osteoarthritis: data from CHECK, a large cohort of individuals with very early symptomatic osteoarthritis. Osteoarthritis Cartilage 2012;20:745-54.
Bos SD, Beekman M, Maier AB, et al. Metabolic health in families enriched for longevity is associated with low prevalence of hand osteoarthritis and influences OA biomarker profiles. Ann Rheum Dis 2013;72:1669-74.