Rev. Soc. Esp. Dolor. 2021; 28(5): 282-291 / DOI: 10.20986/resed.2021.3903/2021
Marcos Edgar Fernández, Olga Susana Pérez, María Jesús Albaladejo, Sandra Álava, María Jesús López, Javier Rodríguez
ABSTRACT
Introduction: Osteoarthritis (OA) is the most common cause of arthritis. Traditionally, OA was viewed as a “wear and tear” disease. However, metabolic and inflammatory factors are now being considered as pathogenic factors to the point that some authors are redefining OA as a “chronic low-grade inflammation” disease.
Evidence: In knee osteoarthritis, many inflammatory signaling pathways and mediators are involved. The new treatment paradigm is based on cellular treatments on the signaling pathways of inflammation, based on cellular and protein components to combat the inflammatory environment of the arthritic joint and regenerate damaged tissue.
Results: The approach of treating only one therapeutic target (nitric oxide inhibitors, nutraceuticals, urate reducing agents, and biologics) that have demonstrated their efficacy in the treatment of inflammatory diseases such as rheumatoid arthritis has not been translated into effective management in OA. A treatment approach aimed simultaneously at multiple targets would be able to manage OA more efficiently. The standard guidelines (AAOS, OARSI, ACR, NICE, or EULAR) do not consider hyaluronic acid, platelet-rich plasma, or ozone, although these treatment options have shown immunomodulatory and healing properties. In this scenario, we hypothesized that hyaluronic acid, platelet-rich plasma, and ozone are promising alternatives for the management of knee OA, due to their multidial properties, as will be seen in this review.
Conclusion: In the present study the pathophysiology of OA has been reviewed, focusing mainly on the inflammatory mechanism, the signaling pathways involved and the possible goals of treatment. Hyaluronic acid, platelet-rich plasma and ozone are proposed as multi-target options for the treatment of knee osteoarthritis.
RESUMEN
Introducción: La osteoartritis (OA) es la causa más común de la artritis. Tradicionalmente, la OA se consideraba como una enfermedad de “desgaste”. Sin embargo, los factores metabólicos e inflamatorios se están considerando ahora como los factores patogénicos hasta el punto de que algunos autores están redefiniendo la OA como una enfermedad de “inflamación crónica de bajo grado”.
Evidencia: En la artrosis de rodilla están involucradas muchas vías de señalización y mediadores inflamatorios. El nuevo paradigma de tratamiento se basa en los tratamientos celulares sobre las vías de señalización de la inflamación, basados en componentes celulares y proteicos para combatir el entorno inflamatorio de la articulación artrósica y regenerar el tejido dañado.
Resultados: El enfoque de tratar solo una diana terapéutica (inhibidores de óxido nítrico, nutracéuticos, agentes reductores de uratos y fármacos biológicos) que han demostrado su eficacia en el tratamiento de enfermedades inflamatorias como la artritis reumatoide no se ha traducido en un manejo eficaz de la OA. Un enfoque de tratamiento dirigido simultáneamente a varias dianas sería capaz de manejar la OA de manera más eficiente. Las pautas estándar (AAOS, OARSI, ACR, NICE o EULAR) no consideran el ácido hialurónico, el plasma rico en plaquetas ni el ozono, aunque estas opciones de tratamiento han mostrado propiedades inmunomoduladoras y curativas. En ese escenario, planteamos la hipótesis de que el ácido hialurónico, el plasma rico en plaquetas y el ozono son alternativas prometedoras para el manejo de la OA de rodilla, debido a sus propiedades multidiana, como se observará en esta revisión.
Conclusión: En el presente estudio se ha revisado la fisiopatología de la OA, centrándose principalmente en el mecanismo inflamatorio, las vías de señalización implicadas y los posibles objetivos del tratamiento. El ácido hialurónico, el plasma rico en plaquetas y el ozono se postulan como opciones de tratamiento multidiana para el tratamiento de la artrosis de rodilla.
Nuevo comentario
Comentarios
No comments in this article
Bibliografía
1. Fernández-Cuadros ME, Pérez-Moro OS, Albaladejo-Florín MJ. Ozone fundamentals and effectiveness in knee pain: Chondromalacia and knee Osteoarthritis. Germany: Lambert Academic Publishing; 2016.
2. Richards MM, Maxwell JS, Weng L, Angelos MG, Golzarian J. Intra-articular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine. Phys Sportsmed. 2016;44(2):101-8.
3. Mobasheri A, Batt M. An update on the pathophysiology of osteoarthritis. Ann Phys Rehabil Med. 2016;59(5-6):333-9.
4. Yeargan A. The Basis for Autologous signaling cell treatment for Osteoarthritic knee pain: Immunologic and Stem Cell signaling Basics. December, 2017. DOI 10.1314/RG.2.2.11757.69604.
5. Jones IA, Togashi R, Wilson ML, Heckmann N, Vangsness CT Jr. Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019;15(2):77-90.
6. Krajewska-Włodarczyk M, Owczarczyk-Saczonek A, Placek W, Osowski A, Wojtkiewicz J. Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy. Int J Mol Sci. 2018;19(2):623.
7. Manoto SL, Maepa MJ, Motaung SK. Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis. Saudi J Biol Sci. 2018;25(4):672-9.
8. Lespasio MJ, Piuzzi NS, Husni ME, Muschler GF, Guarino A, Mont MA. Knee Osteoarthritis: A Primer. Perm J. 2017;21:16-183.
9. Gögebakan B, İzmirli M, Okuyan HM, Ataç L. Biomarkers for Early Diagnosis of Osteoarthritis. In: Osteoarthritis. SM dbooks; 2016.
10. Richards MM, Maxwell JS, Weng L, Angelos MG, Golzarian J. Intra-articular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine. Phys Sportsmed. 2016;44(2):101-8.
11. Manoto SL, Maepa MJ, Motaung SK. Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis. Saudi J Biol Sci. 2018;25(4):672-9.
12. Francisco V, Pino J, Campos-Cabaleiro V, Ruiz-Fernández C, Mera A, Gonzalez-Gay MA, et al. Obesity, Fat Mass and Immune System: Role for Leptin. Front Physiol. 2018 Jun 1;9:640.
13. Courties A, Gualillo O, Berenbaum F, Sellam J. Metabolic stress-induced joint inflammation and osteoarthritis. Osteoarthritis Cartilage. 2015;23(11):1955-65.
14. Denoble AE, Huffman KM, Stabler TV, Kelly SJ, Hershfield MS, McDaniel GE, et al. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc Natl Acad Sci U S A. 2011;108(5):2088-93.
15. McAllister MJ, Chemaly M, Eakin AJ, Gibson DS, McGilligan VE. NLRP3 as a potentially novel biomarker for the management of osteoarthritis. Osteoarthritis Cartilage. 2018;26(5):612-9.
16. Wehmeyer C, Pap T, Buckley CD, Naylor AJ. The role of stromal cells in inflammatory bone loss. Clin Exp Immunol. 2017;189(1):1-11.
17. Pulsatelli L, Addimanda O, Brusi V, Pavloska B, Meliconi R. New findings in osteoarthritis pathogenesis: therapeutic implications. Ther Adv Chronic Dis. 2013;4(1):23-43.
18. Kennedy MI, Whitney K, Evans T, LaPrade RF. Platelet-Rich Plasma and Cartilage Repair. Curr Rev Musculoskelet Med. 2018;11(4):573-82.
19. Mobasheri A, Rayman MP, Gualillo O, Sellam J, van der Kraan P, Fearon U. The role of metabolism in the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2017;13(5):302-11.
20. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21(1):16-21.
21. Wang X, Hunter D, Xu J, Ding C. Metabolic triggered inflammation in osteoarthritis. Osteoarthritis Cartilage. 2015;23(1):22-30.
22. Guisasola MC, Ortiz A, Chana F, Alonso B, Vaquero J. Early inflammatory response in polytraumatized patients: Cytokines and heat shock proteins. A pilot study. Orthop Traumatol Surg Res. 2015;101(5):607-11.
23. Lieberthal J, Sambamurthy N, Scanzello CR. Inflammation in joint injury and post-traumatic osteoarthritis. Osteoarthritis Cartilage. 2015;23(11):1825-34.
24. Mobasheri A. The future of osteoarthritis therapeutics: targeted pharmacological therapy. Curr Rheumatol Rep. 2013;15(10):364.
25. Mazzetti I, Grigolo B, Pulsatelli L, Dolzani P, Silvestri T, Roseti L, et al. Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis. Clin Sci (Lond). 2001;101(6):593-9.
26. Davies CM, Guilak F, Weinberg JB, Fermor B. Reactive nitrogen and oxygen species in interleukin-1-mediated DNA damage associated with osteoarthritis. Osteoarthritis Cartilage. 2008;16(5):624-30.
27. Zhang Z, Leong DJ, Xu L, He Z, Wang A, Navati M, et al. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model. Arthritis Res Ther. 2016;18(1):128.
28. Kuo CF, Chou IJ, See LC, Chen JS, Yu KH, Luo SF, et al. Urate-lowering treatment and risk of total joint replacement in patients with gout. Rheumatology (Oxford). 2018;57(12):2129-39.
29. Leung YY, Haaland B, Huebner JL, Wong SBS, Tjai M, Wang C, Chowbay B, Thumboo J, Chakraborty B, Tan MH, Kraus VB. Colchicine lack of effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): a randomized controlled trial. Osteoarthritis Cartilage. 2018;26(5):631-40.
30. Jones IA, Togashi R, Wilson ML, Heckmann N, Vangsness CT Jr. Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019;15(2):77-90.
31. Helmark IC, Mikkelsen UR, Børglum J, Rothe A, Petersen MC, Andersen O, et al. Exercise increases interleukin-10 levels both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial. Arthritis Res Ther. 2010;12(4):R126.
32. Miller GD, Jenks MZ, Vendela M, Norris JL, Muday GK. Influence of weight loss, body composition, and lifestyle behaviors on plasma adipokines: a randomized weight loss trial in older men and women with symptomatic knee osteoarthritis. J Obes. 2012;2012:708505.
33. Wehling P, Evans C, Wehling J, Maixner W. Effectiveness of intra-articular therapies in osteoarthritis: a literature review. Ther Adv Musculoskelet Dis. 2017;9(8):183-96.
34. Nicholls MA, Fierlinger A, Niazi F, Bhandari M. The Disease-Modifying Effects of Hyaluronan in the Osteoarthritic Disease State. Clin Med Insights Arthritis Musculoskelet Disord. 2017;10:1179544117723611.
35. Moussa M, Lajeunesse D, Hilal G, El Atat O, Haykal G, Serhal R, Chalhoub A, Khalil C, Alaaeddine N. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage. Exp Cell Res. 2017;352(1):146-56.
36. Andia I, Maffulli N. New biotechnologies for musculoskeletal injuries. Surgeon. 2019;17(4):244-55.
37. Ornetti P, Nourissat G, Berenbaum F, Sellam J, Richette P, Chevalier X; under the aegis of the Osteoarthritis Section of the French Society for Rheumatology (Société Française de Rhumatologie, SFR). Does platelet-rich plasma have a role in the treatment of osteoarthritis? Joint Bone Spine. 2016;83(1):31-6.
38. Demange MK, Sisto M, Rodeo S. Future trends for unicompartmental arthritis of the knee: injectables & stem cells. Clin Sports Med. 2014;33(1):161-74.
39. Fernández-Cuadros ME, Perez-Moro OS, Miron-Canelo JA. Could Ozone be used as a feasible future treatment in osteoarthritis of the knee. Diversity Equal Health Care. 2016;13(3):232-9.
40. Fernandez-Cuadros M, Pérez-Moro O, Albaladejo-Florin M, Álava-Rabasa S. Symptomatic (Pain and Inflammation) and Disease-Modifying Effect(Minimal Joint Space) of Intra-articular Ozone (O2-O3)in Osteoarthritis of the Knee: a Clinical Case. SN Compr Clin Med. 2019;1:817-21.
41. Fernandez-Cuadros ME, Perez-Moro OS, Albaladejo-Florin MJ, Algarra-Lopez R. Ozone Decreases Biomarkers of Inflammation (C-Reactive Protein and Erythrocyte Sedimentation Rate) and Improves Pain, Function and Quality of Life in Knee Osteoarthritis Patients: A Before-and-After Study and Review of the Literature. Middle East J Rehabil Health Stud. 2018;5(2):e64507.
42. Fernández-Cuadros ME, Pérez-Moro OS, Albaladejo-Florín MJ, Algarra-Lopez R. Intra Articular Ozone Reduces Serum Uric Acid and Improves Pain, Function and Quality of Life in Knee Osteoarthritis Patients: A Before-and-After Study. Middle East J Rehabil Health. 2018;5(3):e68599.
43. Fernández-Cuadros ME, Pérez-Moro OS, Albaladejo-Florín MJ. Knee osteoarthritis: Condroprotector action and symptomatic effect of ozone on pain, function, quality of life, minimal joint space and knee arthroplasty delay. Middle East J Rehabil Health. 2017;4(1):e43200.
44. Vannabouathong C, Bhandari M, Bedi A, Khanna V, Yung P, Shetty V, et al. Nonoperative Treatments for Knee Osteoarthritis: An Evaluation of Treatment Characteristics and the Intra-Articular Placebo Effect: A Systematic Review. JBJS Rev. 2018;6(7):e5.
45. Arias-Vázquez PI, Tovilla-Zárate CA, Bermudez-Ocaña DY, Legorreta-Ramírez BG, López-Narváez ML. Eficacia de las infiltraciones con ozono en el tratamiento de la osteoartritis de rodilla vs. otros tratamientos intervencionistas: revisión sistemática de ensayos clínicos. Rehabilitación. 2019;53(1):43-55.
46. Noori-Zadeh A, Bakhtiyari S, Khooz R, Haghani K, Darabi S. Intra-articular ozone therapy efficiently attenuates pain in knee osteoarthritic subjects: A systematic review and meta-analysis. Complement Ther Med. 2019;42:240-7.
47. Zamboni F, Vieira S, Reis R, Oliveira M, Collins M. The potential of Hyaluronic Acid in immunoprotection and immunomodulation: chemistry, processing and function. Progr Mat Sci. 2018; 97:97-122.
48. Chen WH, Lo WC, Hsu WC, Wei HJ, Liu HY, Lee CH, et al. Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy. Biomaterials. 2014;35(36):9599-607.
49. Iio K, Furukawa KI, Tsuda E, Yamamoto Y, Maeda S, Naraoka T, et al. Hyaluronic acid induces the release of growth factors from platelet-rich plasma. Asia Pac J Sports Med Arthrosc Rehabil Technol. 2016;4:27-32.
50. Chevalier X, Sheehan B, Whittington C, Pourrahmat MM, Duarte L, Ngai W, et al. Efficacy and Safety of Hylan G-F 20 Versus Intra-Articular Corticosteroids in People with Knee Osteoarthritis: A Systematic Review and Network Meta-Analysis. Clin Med Insights Arthritis Musculoskelet Disord. 2020;13:1179544120967370.
51. Tan J, Chen H, Zhao L, Huang W. Platelet-Rich Plasma Versus Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Meta-analysis of 26 Randomized Controlled Trials. Arthroscopy. 2021;37(1):309-25.
52. Han SB, Seo IW, Shin YS. Intra-Articular Injections of Hyaluronic Acid or Steroids Associated With Better Outcomes Than Platelet-Rich Plasma, Adipose Mesenchymal Stromal Cells, or Placebo in Knee Osteoarthritis: A Network Meta-analysis. Arthroscopy. 2021;37(1):292-306.