Acta Chir Orthop Traumatol Cech. 2025; 92(1):36-43 | DOI: 10.55095/achot2024/051
Biomarkers and Their Role in Understanding OsteoarthritisCurrent concepts review
- 1 Klinika úrazové chirurgie a ortopedie, Ortopedické oddělení, Fakultní nemocnice Ostrava
- 2 Ústav laboratorní medicíny, Oddělení klinické biochemie, Fakultní nemocnice Ostrava
- 3 Katedra chirurgických oborů, Lékařská fakulta, Ostravská univerzita, Ostrava
- 4 Ústav laboratorní medicíny, Lékařská fakulta, Ostravská univerzita, Ostrava
Osteoarthritis (OA) is a degenerative joint disease characterized by progressive damage and loss of articular cartilage with concomitant structural and functional changes in the joint. It is the most common cause of joint pain globally and the resulting productivity loss to the economy. The clinical symptoms of osteoarthritis are mostly determined by the difficulties of patients related to the development of articular degenerative changes, which secondarily lead to joint stiffness and functional limitation. The diagnosis of this disease is currently based on typical clinical symptoms and radiographic findings (e.g. joint space narrowing, osteophytes, subchondral sclerosis, etc.). These parameters, however, are difficult to detect in the early stages of the disease and are most often recognized in the advanced stages. For these reasons, the diagnosis of osteoarthritis is often delayed until irreversible destruction of joint tissue occurs and conservative treatment is less effective. Despite recent scientific progress in understanding the genetic and molecular principles of joint degeneration, currently there is no reliable causal therapy for OA. This review aims to summarize current knowledge of osteoarthritis and possible future directions for diagnosis and early intervention. One of such directions is the study of the so-called biomarkers. A biomarker is defined as an indicator of biological processes and can include radiographic, histological, physiological, or molecular characteristics. In particular, molecular biomarkers are widely studied in knee OA. Attention of the research community is focused on the study of biomarkers as a method of detection and prediction of the early stages of osteoarthritis before irreversible joint damage occurs. Biomarkers help develop more effective and, above all, personalized treatment, thus improve the overall clinical approach to the patient.
Keywords: biomarker, osteoarthritis (OA), clinical phenotype of OA, molecular endotype of OA, DMOADs, personalized treatment
Received: August 27, 2024; Revised: August 27, 2024; Accepted: September 30, 2024; Published: March 13, 2025 Show citation
ACS | AIP | APA | ASA | Harvard | Chicago | Chicago Notes | IEEE | ISO690 | MLA | NLM | Turabian | Vancouver |
References
- ACTRN12622000469718. Te Tauwhiro Turi ma te Rongoa: knee Care for Arthritis through Pharmacy Study. https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12622000469718. 2022;
- Angelini F, Widera P, Mobasheri A, Blair J, Struglics A, Uebelhoer M, et al. Osteoarthritis endotype discovery via clustering of biochemical marker data. Ann Rheum Dis. 2022;81.
Go to original source...
Go to PubMed...
- Arden NK, Perry TA, Bannuru RR, Bruyère O, Cooper C, Haugen IK, et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol. 2021;17.
Go to original source...
Go to PubMed...
- Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27.
Go to original source...
Go to PubMed...
- Bauer DC, Hunter DJ, Abramson SB, Attur M, Corr M, Felson D, et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthritis Cartilage. 2006;14:723-7.
Go to original source...
Go to PubMed...
- Bay-Jensen AC, Reker D, Kjelgaard-Petersen CF, Mobasheri A, Karsdal MA, Ladel C, et al. Osteoarthritis year in review 2015: Soluble biomarkers and the BIPED criteria. Vol. 24, Osteoarthritis and Cartilage. 2016.
Go to original source...
- Bay-Jensen AC, Thudium CS, Mobasheri A. Development and use of biochemical markers in osteoarthritis: Current update. Vol. 30, Current Opinion in Rheumatology. 2018.
Go to original source...
- Bernotiene E, Bagdonas E, Kirdaite G, Bernotas P, Kalvaityte U, Uzieliene I, et al. Emerging Technologies and Platforms for the Immunodetection of Multiple Biochemical Markers in Osteoarthritis Research and Therapy. Vol. 7, Frontiers in Medicine. 2020.
Go to original source...
- Bierma-Zeinstra SM, Van Middelkoop M. Osteoarthritis: In search of phenotypes. Vol. 13, Nature Reviews Rheumatology. 2017.
Go to original source...
- Boffa A, Merli G, Andriolo L, Lattermann C, Salzmann GM, Filardo G. Synovial Fluid Biomarkers in Knee Osteoarthritis: A Systematic Review and Quantitative Evaluation Using BIPEDs Criteria. Vol. 13, Cartilage. 2021.
Go to original source...
- Bruyère O, Honvo G, Veronese N, Arden NK, Branco J, Curtis EM, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Vol. 49, Seminars in Arthritis and Rheumatism. 2019.
Go to original source...
- Daghestani HN, Kraus VB. Inflammatory biomarkers in osteoarthritis. Vol. 23, Osteoarthritis and Cartilage. 2015.
Go to original source...
- Daste C, Kirren Q, Akoum J, Lefèvre-Colau M-M, Rannou F, Nguyen C. Physical activity for osteoarthritis: Efficiency and review of recommandations. Joint Bone Spine. 2021;88:105207.
Go to original source...
Go to PubMed...
- Dell'Isola A, Allan R, Smith SL, Marreiros SSP, Steultjens M. Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature. BMC Musculoskelet Disord. 2016;17.
Go to original source...
Go to PubMed...
- Emery CA, Whittaker JL, Mahmoudian A, Lohmander LS, Roos EM, Bennell KL, et al. Establishing outcome measures in early knee osteoarthritis. Nat Rev Rheumatol. 2019;15.
Go to original source...
Go to PubMed...
- Felson DT. Osteoarthritis as a disease of mechanics. Vol. 21, Osteoarthritis and Cartilage. 2013. p. 10-5.
Go to original source...
Go to PubMed...
- Fosse V, Oldoni E, Bietrix F, Budillon A, Daskalopoulos EP, Fratelli M, et al. Recommendations for robust and reproducible preclinical research in personalised medicine. BMC Med. 2023;21.
Go to original source...
Go to PubMed...
- Gallo J. Osteoartróza. Praha: Maxdorf s.r.o.; 2014. 1-150 p.
- Henrotin Y. Osteoarthritis in year 2021: biochemical markers. Vol. 30, Osteoarthritis and Cartilage. 2022.
Go to original source...
- Huebner JL, Bay-Jensen AC, Huffman KM, He Y, Leeming DJ, McDaniel GE, et al. Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis. Arthritis and Rheumatology. 2014;66.
Go to original source...
Go to PubMed...
- Hunter DJ, March L, Chew M. Osteoarthritis in 2020 and beyond: a Lancet Commission. The Lancet. 2020;396:1711-2.
Go to original source...
Go to PubMed...
- Jørgensen AEM, Kjær M, Heinemeier KM. The effect of aging and mechanical loading on the metabolism of articular cartilage. Vol. 44, Journal of Rheumatology. 2017.
Go to original source...
Go to PubMed...
- Karsdal MA, Tambiah J, Hochberg MC, Ladel C, Bay-Jensen AC, Arendt-Nielsen L, et al. Reflections from the 2021 OARSI clinical trial symposium: Considerations for understanding biomarker assessments in osteoarthritis drug development - Should future studies focus on disease activity, rather than status? In: Osteoarthritis and Cartilage Open. 2022.
Go to original source...
- Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis and Rheumatology. 2020;72.
Go to original source...
Go to PubMed...
- Kraus VB, Blanco FJ, Englund M, Henrotin Y, Lohmander LS, Losina E, et al. OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis. Vol. 23, Osteoarthritis and Cartilage. 2015.
Go to original source...
- Kraus VB, Blanco FJ, Englund M, Karsdal MA, Lohmander LS. Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. Vol. 23, Osteoarthritis and Cartilage. 2015.
Go to original source...
- Kraus VB, Burnett B, Coindreau J, Cottrell S, Eyre D, Gendreau M, et al. Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis. Osteoarthritis Cartilage. 2011;19.
Go to original source...
Go to PubMed...
- Kraus VB, Karsdal MA. Clinical monitoring in osteoarthritis: Biomarkers. Osteoarthritis Cartilage. 2022;30.
Go to original source...
Go to PubMed...
- Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Vol. 17, Osteoarthritis and Cartilage. 2009.
Go to original source...
- Loeser RF, Olex AL, McNulty MA, Carlson CS, Callahan MF, Ferguson CM, et al. Microarray analysis reveals age-related differences in gene expression during the development of osteoarthritis in mice. Arthritis Rheum. 2012;64.
Go to original source...
Go to PubMed...
- Mahmoudian A, Lohmander LS, Mobasheri A, Englund M, Luyten FP. Early-stage symptomatic osteoarthritis of the knee - time for action. Vol. 17, Nature Reviews Rheumatology. 2021.
Go to original source...
- Martin JA, Buckwalter JA. Aging, articular cartilage chondrocyte senescence and osteoarthritis. Vol. 3, Biogerontology. 2002.
Go to original source...
- Mobasheri A. Osteoarthritis year 2012 in review: Biomarkers. Vol. 20, Osteoarthritis and Cartilage. 2012.
Go to original source...
- Mobasheri A, Bay-Jensen AC, van Spil WE, Larkin J, Levesque MC. Osteoarthritis Year in Review 2016: biomarkers (biochemical markers). Vol. 25, Osteoarthritis and Cartilage. 2017.
Go to original source...
- Mobasheri A, Bay-Jensen AC, Gualillo O, Larkin J, Levesque MC, Henrotin Y. Soluble biochemical markers of osteoarthritis: Are we close to using them in clinical practice? Vol. 31, Best Practice and Research: Clinical Rheumatology. 2017.
Go to original source...
- Mobasheri A, Matta C, Zákány R, Musumeci G. Chondrosenescence: Definition, hallmarks and potential role in the pathogenesis of osteoarthritis. Vol. 80, Maturitas. 2015.
Go to original source...
- Mobasheri A, Saarakkala S, Finnilä M, Karsdal MA, Bay-Jensen AC, van Spil WE. Recent advances in understanding the phenotypes of osteoarthritis. Vol. 8, F1000Research. 2019.
Go to original source...
Go to PubMed...
- Mobasheri A, Van Spil WE, Budd E, Uzieliene I, Bernotiene E, Bay-Jensen AC, et al. Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: Biochemical markers associated with emerging clinical phenotypes and molecular endotypes. Vol. 31, Current Opinion in Rheumatology. 2019.
Go to original source...
- Mobasheri A, Thudium CS, Bay-Jensen AC, Maleitzke T, Geissler S, Duda GN, et al. Biomarkers for osteoarthritis: Current status and future prospects. Best Pract Res Clin Rheumatol. 2023;101852.
Go to original source...
Go to PubMed...
- Oo WM. Prospects of Disease-Modifying Osteoarthritis Drugs. Clin Geriatr Med. 2022;38:397-432.
Go to original source...
Go to PubMed...
- Owens C, Conaghan PG. Improving joint pain and function in osteoarthritis. In: Practitioner. 2016.
- Panagopoulos PK, Lambrou GI. The involvement of micrornas in osteoarthritis and recent developments: A narrative review. Vol. 29, Mediterranean Journal of Rheumatology. 2018.
Go to original source...
Go to PubMed...
- Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Vol. 12, Nature Reviews Rheumatology. Nature Publishing Group; 2016. p. 580-92.
Go to original source...
Go to PubMed...
- Rocha FAC, Ali SA. Soluble biomarkers in osteoarthritis in 2022: year in review. Vol. 31, Osteoarthritis and Cartilage. 2023.
Go to original source...
- Scanzello CR. Role of low-grade inflammation in osteoarthritis. Vol. 29, Current Opinion in Rheumatology. 2017.
Go to original source...
- van Spil WE, DeGroot J, Lems WF, Oostveen JCM, Lafeber FPJG. Serum and urinary biochemical markers for knee and hip-osteoarthritis: A systematic review applying the consensus BIPED criteria. Vol. 18, Osteoarthritis and Cartilage. 2010.
Go to original source...
- van Spil WE, Szilagyi IA. Osteoarthritis year in review 2019: biomarkers (biochemical markers). Vol. 28, Osteoarthritis and Cartilage. 2020.
Go to original source...
- Van Spil WE, Kubassova O, Boesen M, Bay-Jensen AC, Mobasheri A. Osteoarthritis phenotypes and novel therapeutic targets. Vol. 165, Biochemical Pharmacology. 2019.
Go to original source...
- Wen C, Xiao G. Advances in osteoarthritis research in 2021 and beyond. J Orthop Translat. 2022;32:A1-2.
Go to original source...
Go to PubMed...
- Zheng L, Zhang Z, Sheng P, Mobasheri A. The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis. Vol. 66, Ageing Research Reviews. 2021.
Go to original source...
- OARSI Definition of OA. https://oarsi.org/research/standardization-osteoarthritis-definitions.