Osteoarthritis: A contemporary view of the problem, the possibilities of therapy and prospects for further research

Lina Zaripova 1 * , Damira Tazhibayeva 2, Natalya Kabdualieva 2, Zhayna Aitbayeva 2, Gulshakhar Beglarova 2, Lazzat Yermentayeva 2, Karlygash Niyazbekova 2
More Detail
1 Scientific and Innovation Management Department, National Scientific Medical Center, Astana, Kazakhstan
2 Department of Pathological Physiology named after V.G.Korpachev, Astana Medical University, Astana, Kazakhstan
* Corresponding Author
J CLIN MED KAZ, In press. https://doi.org/10.23950/jcmk/12629


Osteoarthritis is a chronic degenerative disease characterized by the destructive changes in the articular cartilage, synovitis, subchondral bone sclerosis and osteophyte formation. Today it is the most common joint disease and one of the main causes of disability of elderly people.
This review provides an overview of advances in understanding of osteoarthritis etiology, pathogenesis, histopathology, as well as the results of up-to-date research of the molecular mechanisms underlying this heterogeneous age-related disease at the clinical and fundamental levels.
The article is devoted to a comprehensive review of the osteoarthritis problem, compiled considering the classical understanding of morphological changes, clinical picture, diagnostic methods, and current therapy protocols, supplemented by the modern trends of world research with the prospect of further development and implementation of the latest therapeutic methods, such as nerve growth factor-inhibitors, fibroblast growth factor-18 and stem cells treatments.


Zaripova L, Tazhibayeva D, Kabdualieva N, Aitbayeva Z, Beglarova G, Yermentayeva L, et al. Osteoarthritis: A contemporary view of the problem, the possibilities of therapy and prospects for further research. J Clin Med Kaz. 2022. https://doi.org/10.23950/jcmk/12629


  • Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis and rheumatism. 1998;41(5):778-799. https://doi.org/10.1002/1529-0131(199805)41:5<778::AID-ART4>3.0.CO;2-V
  • Hawker GA. Osteoarthritis is a serious disease. Clinical and experimental rheumatology. 2019;37(Suppl 120):3-6.
  • Culliford D, Maskell J, Judge A, Cooper C, Prieto-Alhambra D, Arden NK. Future projections of total hip and knee arthroplasty in the UK: results from the UK Clinical Practice Research Datalink. Osteoarthritis and cartilage. 2015;23(4):594-600. https://doi.org/10.1016/j.joca.2014.12.022
  • Veronese N, Cereda E, Maggi S, Luchini C, Solmi M, Smith T, et al. Osteoarthritis and mortality: A prospective cohort study and systematic review with meta-analysis. Seminars in arthritis and rheumatism. 2016;46(2):160-167. https://doi.org/10.1016/j.semarthrit.2016.04.002
  • Chen D, Shen J, Zhao W, Wang T, Han L, Hamilton JL, et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone research. 2017;5:16044. https://doi.org/10.1038/boneres.2016.44
  • Man GS, Mologhianu G. Osteoarthritis pathogenesis - a complex process that involves the entire joint. Journal of medicine and life. 2014;7(1):37-41.
  • Tan Q, Jiang A, Li W, Song C, Leng H. Metabolic syndrome and osteoarthritis: Possible mechanisms and management strategies. Medicine in Novel Technology and Devices. 2021;9:100052. https://doi.org/10.1016/j.medntd.2020.100052
  • Chen D, Shen J, Zhao W, Wang T, Han L, Hamilton JL, et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone research. 2017;5:16044-16044. https://doi.org/10.1038/boneres.2016.44
  • Pelletier J-P, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: Potential implication for the selection of new therapeutic targets. Arthritis & Rheumatism. 2001;44(6):1237-1247. https://doi.org/10.1002/1529-0131(200106)44:6<1237::AID-ART214>3.0.CO;2-F
  • Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nature Reviews Rheumatology. 2015;11(1):35-44. https://doi.org/10.1038/nrrheum.2014.162
  • Teoh YX, Lai KW, Usman J, Goh SL, Mohafez H, Hasikin K, et al. Discovering Knee Osteoarthritis Imaging Features for Diagnosis and Prognosis: Review of Manual Imaging Grading and Machine Learning Approaches. Journal of healthcare engineering. 2022;2022:4138666. https://doi.org/10.1155/2022/4138666
  • Maghbooli Z, Hossein-Nezhad A, Khoshechin G, Niketeghad G, Moradi S, Adabi E, et al. Possible association between circulating CTRP3 and knee osteoarthritis in postmenopausal women. Aging Clin Exp Res. 2019;31(7):927-934. https://doi.org/10.1007/s40520-018-1035-5
  • 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. Nature reviews Rheumatology. 2021;17(1):59-66. https://doi.org/10.1038/s41584-020-00523-9
  • Vitaloni M, Botto-van Bemden A, Sciortino R, Carné X, Quintero M, Santos-Moreno P, et al. A patients’ view of OA: the Global Osteoarthritis Patient Perception Survey (GOAPPS), a pilot study. BMC Musculoskeletal Disorders. 2020;21(1):727. https://doi.org/10.1186/s12891-020-03741-0
  • Thomas S, Browne H, Mobasheri A, Rayman MP. What is the evidence for a role for diet and nutrition in osteoarthritis? Rheumatology (Oxford, England). 2018;57(suppl_4):iv61-iv74. https://doi.org/10.1093/rheumatology/key011
  • 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 care & research. 2020;72(2):149-162. https://doi.org/10.1002/acr.24131
  • 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 and cartilage. 2019;27(11):1578-1589. https://doi.org/10.1016/j.joca.2019.06.011
  • Abate M, Vanni D, Pantalone A, Salini V. Hyaluronic acid in knee osteoarthritis: preliminary results using a four months administration schedule. International journal of rheumatic diseases. 2017;20(2):199-202. https://doi.org/10.1111/1756-185X.12572
  • Honvo G, Reginster JY, Rabenda V, Geerinck A, Mkinsi O, Charles A, et al. Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. Drugs & aging. 2019;36(Suppl 1):65-99. https://doi.org/10.1007/s40266-019-00662-z
  • Eriksen P, Bartels EM, Altman RD, Bliddal H, Juhl C, Christensen R. Risk of bias and brand explain the observed inconsistency in trials on glucosamine for symptomatic relief of osteoarthritis: a meta-analysis of placebo-controlled trials. Arthritis care & research. 2014;66(12):1844-1855. https://doi.org/10.1002/acr.22376
  • Rönn K, Reischl N, Gautier E, Jacobi M. Current surgical treatment of knee osteoarthritis. Arthritis. 2011;2011:454873. https://doi.org/10.1155/2011/454873
  • Lauwers M, Au M, Yuan S, Wen C. COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives. Int J Mol Sci. 2022;23(2). https://doi.org/10.3390/ijms23020720
  • Alhassan E, Siaton BC, Hochberg MC. Did COVID-19 impact osteoarthritis - clinical perspective? Current opinion in rheumatology. 2022;34(1):68-72. https://doi.org/10.1097/BOR.0000000000000851
  • Quicke JG, Conaghan PG, Corp N, Peat G. Osteoarthritis year in review 2021: epidemiology &amp; therapy. Osteoarthritis and cartilage. 2022;30(2):196-206. https://doi.org/10.1016/j.joca.2021.10.003
  • Pavlovic V, Ciric M, Jovanovic V, Stojanovic P. Platelet Rich Plasma: a short overview of certain bioactive components. Open medicine (Warsaw, Poland). 2016;11(1):242-247. https://doi.org/10.1515/med-2016-0048
  • Hong M, Cheng C, Sun X, Yan Y, Zhang Q, Wang W, et al. Efficacy and Safety of Intra-Articular Platelet-Rich Plasma in Osteoarthritis Knee: A Systematic Review and Meta-Analysis. BioMed Research International. 2021;2021:2191926. https://doi.org/10.1155/2021/2191926
  • Abate M, Verna S, Schiavone C, Di Gregorio P, Salini V. Efficacy and safety profile of a compound composed of platelet-rich plasma and hyaluronic acid in the treatment for knee osteoarthritis (preliminary results). European journal of orthopaedic surgery & traumatology : orthopedie traumatologie. 2015;25(8):1321-1326. https://doi.org/10.1007/s00590-015-1693-3
  • Dório M, Pereira RMR, Luz AGB, Deveza LA, de Oliveira RM, Fuller R. Efficacy of platelet-rich plasma and plasma for symptomatic treatment of knee osteoarthritis: a double-blinded placebo-controlled randomized clinical trial. BMC Musculoskeletal Disorders. 2021;22(1):822. https://doi.org/10.1186/s12891-021-04706-7
  • Arthroscopy Association of C, Kopka M, Sheehan B, Degen R, Wong I, Hiemstra L, et al. Arthroscopy Association of Canada Position Statement on Intra-articular Injections for Knee Osteoarthritis. Orthop J Sports Med. 2019;7(7):2325967119860110-2325967119860110. https://doi.org/10.1177/2325967119860110
  • Smolewska E, Cebula B, Brozik H, Stanczyk J. Relationship between impaired apoptosis of lymphocytes and distribution of dendritic cells in peripheral blood and synovial fluid of children with juvenile idiopathic arthritis. Arch Immunol Ther Exp (Warsz). 2008;56(4):283-289. https://doi.org/10.1007/s00005-008-0030-5
  • Vercoulen Y, Wehrens EJ, van Teijlingen NH, de Jager W, Beekman JM, Prakken BJ. Human regulatory T cell suppressive function is independent of apoptosis induction in activated effector T cells. PLoS One. 2009;4(9):e7183. https://doi.org/10.1371/journal.pone.0007183
  • Jones EA, Crawford A, English A, Henshaw K, Mundy J, Corscadden D, et al. Synovial fluid mesenchymal stem cells in health and early osteoarthritis: detection and functional evaluation at the single-cell level. Arthritis and rheumatism. 2008;58(6):1731-1740. https://doi.org/10.1002/art.23485
  • de Sousa EB, Casado PL, Moura Neto V, Duarte ME, Aguiar DP. Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives. Stem cell research & therapy. 2014;5(5):112. https://doi.org/10.1186/scrt501
  • Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, et al. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nature Biotechnology. 2008;26(11):1269-1275. https://doi.org/10.1038/nbt.1502
  • Welch T, Mandelbaum B, Tom M. Autologous Chondrocyte Implantation: Past, Present, and Future. Sports medicine and arthroscopy review. 2016;24(2):85-91. https://doi.org/10.1097/JSA.0000000000000115
  • Welzel T, Winskill C, Zhang N, Woerner A, Pfister M. Biologic disease modifying antirheumatic drugs and Janus kinase inhibitors in paediatric rheumatology - what we know and what we do not know from randomized controlled trials. Pediatric rheumatology online journal. 2021;19(1):46. https://doi.org/10.1186/s12969-021-00514-4
  • Feist E, Baraliakos X, Behrens F, Thaçi D, Klopsch T, Plenske A, et al. Effectiveness of Etanercept in Rheumatoid Arthritis: Real-World Data from the German Non-interventional Study ADEQUATE with Focus on Treat-to-Target and Patient-Reported Outcomes. Rheumatology and Therapy. 2022;9(2):621-635. https://doi.org/10.1007/s40744-021-00418-5
  • Aitken D, Laslett LL, Pan F, Haugen IK, Otahal P, Bellamy N, et al. A randomised double-blind placebo-controlled crossover trial of HUMira (adalimumab) for erosive hand OsteoaRthritis - the HUMOR trial. Osteoarthritis and cartilage. 2018;26(7):880-887. https://doi.org/10.1016/j.joca.2018.02.899
  • Kloppenburg M, Peterfy C, Haugen IK, Kroon F, Chen S, Wang L, et al. Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis. Ann Rheum Dis. 2019;78(3):413-420. https://doi.org/10.1136/annrheumdis-2018-213336
  • Fleischmann RM, Bliddal H, Blanco FJ, Schnitzer TJ, Peterfy C, Chen S, et al. A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis. Arthritis & rheumatology (Hoboken, NJ). 2019;71(7):1056-1069. https://doi.org/10.1002/art.40840
  • Richette P, Latourte A, Sellam J, Wendling D, Piperno M, Goupille P, et al. Efficacy of tocilizumab in patients with hand osteoarthritis: double blind, randomised, placebo-controlled, multicentre trial. Annals of the Rheumatic Diseases. 2021;80(3):349-355. https://doi.org/10.1136/annrheumdis-2020-218547
  • Schnitzer TJ, Marks JA. A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip or knee. Osteoarthritis and cartilage. 2015;23:S8-S17. https://doi.org/10.1016/j.joca.2014.10.003
  • Pallav M, Zaripova L, Tazhibaeva D, Kabdualieva N. POS1126 Сlinical efficacy and safety of monoclonal antibody against nerve growth factor and fibroblast growth factor-18 therapy of osteoarthritis. Annals of the Rheumatic Diseases. 2022;81(Suppl 1):892-892. https://doi.org/10.1136/annrheumdis-2022-eular.3584
  • Vinatier C, Merceron C, Guicheux J. Osteoarthritis: from pathogenic mechanisms and recent clinical developments to novel prospective therapeutic options. Drug Discovery Today. 2016;21(12):1932-1937. https://doi.org/10.1016/j.drudis.2016.08.011
  • Dakin P, DiMartino SJ, Gao H, Maloney J, Kivitz AJ, Schnitzer TJ, et al. The Efficacy, Tolerability, and Joint Safety of Fasinumab in Osteoarthritis Pain: A Phase IIb/III Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Arthritis & rheumatology (Hoboken, NJ). 2019;71(11):1824-1834. https://doi.org/10.1002/art.41012
  • Lohmander LS, Hellot S, Dreher D, Krantz EFW, Kruger DS, Guermazi A, et al. Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis & Rheumatology. 2014;66(7):1820-1831. https://doi.org/10.1002/art.38614
  • Hochberg MC, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P, et al. Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial. Jama. 2019;322(14):1360-1370. https://doi.org/10.1001/jama.2019.14735
  • Li H, Ding X, Terkeltaub R, Lin H, Zhang Y, Zhou B, et al. Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior. Arthritis Res Ther. 2020;22(1):34. https://doi.org/10.1186/s13075-020-2129-y
  • van Meurs JB. Osteoarthritis year in review 2016: genetics, genomics and epigenetics. Osteoarthritis and cartilage. 2017;25(2):181-189. https://doi.org/10.1016/j.joca.2016.11.011
  • Kostopoulou F, Malizos KN, Papathanasiou I, Tsezou A. MicroRNA-33a regulates cholesterol synthesis and cholesterol efflux-related genes in osteoarthritic chondrocytes. Arthritis Res Ther. 2015;17(1):42. https://doi.org/10.1186/s13075-015-0556-y
  • Song J, Kim D, Chun C-H, Jin E-J. miR-370 and miR-373 regulate the pathogenesis of osteoarthritis by modulating one-carbon metabolism via SHMT-2 and MECP-2, respectively. Aging Cell. 2015;14(5):826-837. https://doi.org/10.1111/acel.12363
  • Li L, Jia J, Liu X, Yang S, Ye S, Yang W, et al. MicroRNA-16-5p Controls Development of Osteoarthritis by Targeting SMAD3 in Chondrocytes. Current pharmaceutical design. 2015;21(35):5160-5167. https://doi.org/10.2174/1381612821666150909094712
  • Rasheed Z, Al-Shobaili HA, Rasheed N, Mahmood A, Khan MI. MicroRNA-26a-5p regulates the expression of inducible nitric oxide synthase via activation of NF-κB pathway in human osteoarthritis chondrocytes. Archives of Biochemistry and Biophysics. 2016;594:61-67. https://doi.org/10.1016/j.abb.2016.02.003
  • Tu M, Li Y, Zeng C, Deng Z, Gao S, Xiao W, et al. MicroRNA-127-5p regulates osteopontin expression and osteopontin-mediated proliferation of human chondrocytes. Sci Rep. 2016;6(1):25032. https://doi.org/10.1038/srep25032
  • Hu W, Zhang W, Li F, Guo F, Chen A. miR-139 is up-regulated in osteoarthritis and inhibits chondrocyte proliferation and migration possibly via suppressing EIF4G2 and IGF1R. Biochemical and Biophysical Research Communications. 2016;474(2):296-302. https://doi.org/10.1016/j.bbrc.2016.03.164