Skip to main content

The Concept of Early Osteoarthritis and Its Significance in Regenerative Medicine


Osteoarthritis (OA) has been investigated as one of important target diseases for regenerative medicine. The concept of early OA has recently emerged under the assumption that if OA is detected and intervened early, progression of OA might be arrested or delayed before irreversible destruction of the joint occurs. This concept also matters in regenerative medicine for OA because new regenerative technologies can work better when joint damage is minimal. Diagnostic criteria for early OA have been suggested in this background to find a group of patients who have a higher possibility of developing full-blown OA. However, as currently suggested criteria of early OA are mostly expert opinions lacking higher level of evidence, clinical validations are necessary to prove their value in patient care. While new treatment methods that can suppress or prevent symptoms at an early stage of OA before progressive and irreversible changes occur are being developed, detailed definition and classification of early OA agreed upon by major stakeholders in OA field and validated by prospective studies are necessary to prove the efficacy of these methods. As clinical outcome of regenerative treatment is related to patient characteristics and the status of the whole joint, it is of critical significance to predict which patient will progress and who will be responsive to regenerative treatment. While diagnostic criteria for early OA should be highly sensitive and applicable without employing biomarkers or magnetic resonance imaging, a subclassification and comprehensive endotyping /phenotyping using these techniques might be needed to detect the population who would be responsive to regenerative medicine.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16:494–502.

    CAS  Article  Google Scholar 

  2. Risberg MA, Holm I, Tjomsland O, Ljunggren E, Ekeland A. Prospective study of changes in impairments and disabilities after anterior cruciate ligament reconstruction. J Orthop Sports Phys Ther. 1999;29:400–12.

    CAS  Article  Google Scholar 

  3. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria committee of the American Rheumatism Association. Arthritis Rheum. 1986;29:1039–49.

    CAS  Article  Google Scholar 

  4. Altman R, Alarcón G, Appelrouth D, Bloch D, Borestein D, Brandt K, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum. 1991;34:505–14.

    CAS  Article  Google Scholar 

  5. Kanamoto T, Mae T, Yokoyama T, Tanaka H, Ebina K, Nakata K. Significance and definition of early knee osteoarthritis. Ann Joint. 2020;5:4.

    Article  Google Scholar 

  6. Luyten FP, Denti M, Filardo G, Kon E, Engebretsen L. Definition and classification of early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2012;20:401–6.

    Article  Google Scholar 

  7. Mahmoudian A, Lohmander LS, Mobasheri A, Englund M, Luyten FP. Early-stage symptomatic osteoarthritis of the knee - time for action. Nat Rev Rheumatol. 2021;17:621–32.

    Article  Google Scholar 

  8. Madry H, Kon E, Condello V, Peretti GM, Steinwachs M, Seil R, et al. Early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2016;24:1753–62.

    Article  Google Scholar 

  9. Migliore A, Scirè CA, Carmona L, Beaumont GH, Bizzi E, Branco J, et al. The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology. Rheumatol Int. 2017;37:1227–36.

    Article  Google Scholar 

  10. Luyten FP, Bierma-Zeinstra S, Dell’Accio F, Kraus VB, Nakata K, Sekiya I, et al. Toward classification criteria for early osteoarthritis of the knee. Semin Arthritis Rheum. 2018;47:457–63.

    CAS  Article  Google Scholar 

  11. Mahmoudian A, Lohmander LS, Jafari H, Luyten FP. Towards classification criteria for early-stage knee osteoarthritis: a population-based study to enrich for progressors. Semin Arthritis Rheum. 2021;51:285–91.

    Article  Google Scholar 

  12. Culvenor AG, Collins NJ, Guermazi A, Cook JL, Vicenzino B, Khan KM, et al. Early knee osteoarthritis is evident one year following anterior cruciate ligament reconstruction: a magnetic resonance imaging evaluation. Arthritis Rheumatol. 2015;67:946–55.

    CAS  Article  Google Scholar 

  13. Madry H, Luyten FP, Facchini A. Biological aspects of early osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012;20:407–22.

    Article  Google Scholar 

  14. Case R, Thomas E, Clarke E, Peat G. Prodromal symptoms in knee osteoarthritis: a nested case-control study using data from the osteoarthritis initiative. Osteoarthritis Cartilage. 2015;23:1083–9.

    CAS  Article  Google Scholar 

  15. Van Spil WE, Welsing PM, Bierma-Zeinstra SM, Bijlsma JW, Roorda LD, Cats HA, et al. The ability of systemic biochemical markers to reflect presence, incidence, and progression of early-stage radiographic knee and hip osteoarthritis: data from CHECK. Osteoarthritis Cartilage. 2015;23:1388–97.

    Article  Google Scholar 

  16. Chu CR, Williams AA, Coyle CH, Bowers ME. Early diagnosis to enable early treatment of pre-osteoarthritis. Arthritis Res Ther. 2012;14:212.

    Article  Google Scholar 

  17. Gelber AC, Hochberg MC, Mead LA, Wang NY, Wigley FM, Klag MJ. Joint injury in young adults and risk for subsequent knee and hip osteoarthritis. Ann Intern Med. 2000;133:321–8.

    CAS  Article  Google Scholar 

  18. Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequences of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007;35:1756–69.

    Article  Google Scholar 

  19. Hawker GA, Lohmander LS. What an earlier recognition of osteoarthritis can do for OA prevention. Osteoarthritis Cartilage. 2021;29:1632–4.

Download references


Funding was provided by Korea Health Industry Development Institute (Grant No. HI20C0090) and National research Foundation of Korea (Grant No. NRF-2020R1A2C2008266).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Gun-Il Im.

Ethics declarations

Conflict of interest


Ethical Statement

There are no animal experiements carried out for this article.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Im, GI. The Concept of Early Osteoarthritis and Its Significance in Regenerative Medicine. Tissue Eng Regen Med 19, 431–436 (2022).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Early osteoarthritis
  • Regenerative medicine
  • Validation