Отсрочка оперативного лечения при остеоартрите коленных суставов: эффективность и преимущества использования гиалуроната натрия с поперечными межмолекулярными связями

Теплякова О.В., Жиляков А.В. Отсрочка оперативного лечения при остеоартрите коленных суставов: эффективность и преимущества использования гиалуроната натрия с поперечными межмолекулярными связями. Consilium Medicum. 2025;27(11):697–704. DOI: 10.26442/20751753.2025.11.203448

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Teplyakova OV, Zhilyakov AV. Delaying surgery for knee osteoarthritis: efficacy and benefits of using cross-linked sodium hyaluronate. A review. Consilium Medicum. 2025;27(11):697–704. DOI: 10.26442/20751753.2025.11.203448

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Аннотация

Распространенность остеоартрита (ОА) коленных суставов (КС), демонстрирующая неуклонный рост в последние десятилетия, представляет собой серьезную клиническую и экономическую проблему. Подобная ситуация обусловливает активный поиск эффективных методов консервативного лечения, способных замедлить прогрессирование заболевания и отсрочить необходимость тотального эндопротезирования КС (ТЭКС). В статье приводится детальный анализ современного места внутрисуставного введения препаратов гиалуроновой кислоты (ГК) в лечении ОА. Обосновывается необходимость персонализированного подхода к лечению, основанного на фенотипировании ОА, предлагаются консенсусные рекомендации Европейской консенсусной группы по вискосупплементации – EUROVISCO, которые определяют конкретные клинические ситуации для рационального применения ГК. Особое внимание уделяется препаратам ГК с поперечными межмолекулярными связями (кросс-линкам), которые благодаря увеличенному времени нахождения в суставе обеспечивают как продолжительный механический (амортизационный), так и отсроченный биологический (вискоиндукцию) эффекты. Рассматриваются преимущества инновационной технологии Crosslinked Hyaluronic Acid Platform – CHAP, реализованной в препарате Флексотрон Кросс®, позволяющей достичь более быстрого и выраженного эффекта по сравнению с другими кросс-линками. Приводятся данные, демонстрирующие влияние курсового применения ГК на возможность значительно отсрочить сроки проведения ТЭКС, предоставляя пациентам возможность для модификации образа жизни, в частности для снижения массы тела, что существенно уменьшает периоперационные риски. Дополнительно освещается проблема прогрессирования ОА в контралатеральном суставе после одностороннего ТЭКС и обсуждается протективная роль ГК в предотвращении его повреждения за счет снижения боли и нормализации паттернов движения.

Ключевые слова: остеоартрит, гиалуроновая кислота, кросс-линк, тотальное эндопротезирование, контралатеральный сустав

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The prevalence of knee osteoarthritis (OA), which has been steadily increasing in recent decades, represents a serious clinical and economic problem. This situation necessitates an active search for effective conservative treatment methods capable of slowing disease progression and delaying the need for total knee arthroplasty (TKA). This article presents a detailed analysis of the current role of intra-articular administration of hyaluronic acid (HA) preparations in OA therapy. The necessity of personalized treatment approach based on OA phenotyping is justified, and consensus recommendations from the European expert group EUROVISCO are provided, defining specific clinical situations for rational use of HA. Special attention is given to cross-linked HA drugs that, due to their prolonged residence time in the joint, provide both long-lasting mechanical (shock absorption) and delayed biological (viscoinduction) effects. Advantages of the innovative CHAP technology implemented in Flexotron Cross® drug are discussed, allowing achieving faster and more pronounced analgesic effect compared to other cross-links. Data demonstrating the impact of course application of HA on significantly postponing TKA timelines are presented, providing patients with opportunities for lifestyle modification, particularly weight loss, which substantially reduces perioperative risks. Additionally, the issue of contralateral joint OA progression after unilateral TKA is addressed, discussing protective role of HA in preventing its damage by reducing pain and normalizing movement patterns.

Keywords: osteoarthritis, hyaluronic acid, cross-link, total arthroplasty, contralateral joint

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1. Long H, Liu Q, Yin H, et al. Prevalence Trends of Site-Specific Osteoarthritis From 1990 to 2019: Findings From the Global Burden of Disease Study 2019. Arthritis Rheumatol. 2022;74(7):1172-213. DOI:10.1002/art.42089
2. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745-79. DOI:10.1016/S0140-6736(19)30417-9
3. O'Neill TW, McCabe PS, McBeth J. Update on the epidemiology, risk factors and disease outcomes of osteoarthritis. Best Pract Res Clin Rheumatol. 2018;32(2):312-26. DOI:10.1016/j.berh.2018.10.007
4. Peck J, Slovek A, Miro P, et al. A Comprehensive Review of Viscosupplementation in Osteoarthritis of the Knee. Orthop Rev (Pavia). 2021;13(2):25549. DOI:10.52965/001c.25549
5. Migliore A, Gigliucci G, Alekseeva L, et al. Systematic Literature Review and Expert Opinion for the Use of Viscosupplementation with Hyaluronic Acid in Different Localizations of Osteoarthritis. Orthop Res Rev. 2021;13:255-73. DOI:10.2147/ORR.S336185
6. Pavone V, Vescio A, Turchetta M, et al. Injection-Based Management of Osteoarthritis of the Knee: A Systematic Review of Guidelines. Front Pharmacol. 2021;12:661805. DOI:10.3389/fphar.2021.661805
7. Bannuru RR, Schmid CH, Kent DM, et al. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162(1):46-54. DOI:10.7326/M14-1231
8. Allied Market Research. Viscosupplementation market research, 2031. Available at: https://www.alliedmarketresearch.com/viscosupplementation-market. Accessed: 28.08.2024.
9. Pereira TV, Jüni P, Saadat P, et al. Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis. BMJ. 2022;378:e069722. DOI:10.1136/bmj-2022-069722
10. Katz JN, Arant KR, Loeser RF. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA. 2021;325(6):568-78. DOI:10.1001/jama.2020.22171
11. Osteoartrit kolennogo sustava. Klinicheskie rekomendatsii Minzdrava Rossii. Available at: https://cr.minzdrav.gov.ru/schema/667_1. Accessed: 28.08.2024 (in Russian).
12. Gibbs AJ, Gray B, Wallis JA, et al. Recommendations for the management of hip and knee osteoarthritis: A systematic review of clinical practice guidelines. Osteoarthritis Cartilage. 2023;31(10):1280-322. DOI:10.1016/j.joca.2023.05.015
13. Van Spil WE, Kubassova O, Boesen M, et al. Osteoarthritis phenotypes and novel therapeutic targets. Biochem Pharmacol. 2019;165:41-8. DOI:10.1016/j.bcp.2019.02.037
14. Sellam J, Courties A, Eymard F, et al. Recommendations of the French Society of Rheumatology on pharmacological treatment of knee osteoarthritis. Joint Bone Spine. 2020;87(6):548-55. DOI:10.1016/j.jbspin.2020.09.004
15. Raman R, Henrotin Y, Chevalier X, et al. Decision Algorithms for the Retreatment with Viscosupplementation in Patients Suffering from Knee Osteoarthritis: Recommendations from the EUROpean VIScosupplementation COnsensus Group (EUROVISCO). Cartilage. 2018;9(3):263-75. DOI:10.1177/1947603517693043
16. Conrozier T, Raman R, Chevalier X, et al. Viscosupplementation for the treatment of osteoarthritis. The contribution of EUROVISCO group. Ther Adv Musculoskelet Dis. 2021;13:1759720X211018605. DOI:10.1177/1759720X211018605
17. Conrozier T, Raman R, Diraçoglu D, et al. EUROVISCO Consensus Guidelines for the Use of Hyaluronic Acid Viscosupplementation in Knee Osteoarthritis Based on Patient Characteristics. Cartilage. 2024:19476035241271970. DOI:10.1177/19476035241271970
18. Monfort J, Henrotin Y, Chevalier X, et al. EUROVISCO Good Medical Practice Recommendations for the Use of Viscosupplementation with Hyaluronic Acid in the Management of Knee Osteoarthritis. Cartilage. 2025:19476035241286578. DOI:10.1177/19476035241286578
19. Hyaluronic acid preparations in traumatology and orthopedics. Orthobiological aspects. Consensus draft. Traumatology and orthopedics of Russia. 2024;30(2):215-30 (in Russian).
20. Fallacara A, Baldini E, Manfredini S, Vertuani S. Hyaluronic Acid in the Third Millennium. Polymers (Basel). 2018;10(7):701. DOI:10.3390/polym10070701
21. Wu Y, Zhao S, Wang J, et al. Methods for determining the structure and physicochemical properties of hyaluronic acid and its derivatives: A review. Int J Biol Macromol. 2024;282(Pt 6):137603. DOI:10.1016/j.ijbiomac.2024.137603
22. Vigetti D, Karousou E, Viola M, et al. Hyaluronan: biosynthesis and signaling. Biochim Biophys Acta. 2014;1840(8):2452-9. DOI:10.1016/j.bbagen.2014.02.001
23. Felson DT, Anderson JJ. Hyaluronate sodium injections for osteoarthritis: hope, hype, and hard truths. Arch Intern Med. 2002;162(3):245-7. DOI:10.1001/archinte.162.3.245
24. Sindelar M, Jilkova J, Kubala L, et al. Hyaluronidases and hyaluronate lyases: From humans to bacteriophages. Colloids Surf B Biointerfaces. 2021;208:112095. DOI:10.1016/j.colsurfb.2021.112095
25. Berdiaki A, Neagu M, Spyridaki I, et al. Hyaluronan and Reactive Oxygen Species Signaling-Novel Cues from the Matrix? Antioxidants (Basel). 2023;12(4):824. DOI:10.3390/antiox12040824
26. Volpi N, Schiller J, Stern R, Soltés L. Role, metabolism, chemical modifications and applications of hyaluronan. Curr Med Chem. 2009;16(14):1718-45. DOI:10.2174/092986709788186138
27. Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl.):S28-33. DOI:10.1016/j.semarthrit.2015.11.008
28. Henrotin Y, Raman R, Richette P, et al. Consensus statement on viscosupplementation with hyaluronic acid for the management of osteoarthritis. Semin Arthritis Rheum. 2015;45(2):140-9. DOI:10.1016/j.semarthrit.2015.04.011
29. De Boulle K, Glogau R, Kono T, et al. A review of the metabolism of 1,4-butanediol diglycidyl ether-crosslinked hyaluronic acid dermal fillers. Dermatol Surg. 2013;39(12):1758-66. DOI:10.1111/dsu.12301
30. Zhang T, Zhao S, Chen Y, et al. In-depth characterization of 1,4-butanediol diglycidyl ether substituted hyaluronic acid hydrogels. Carbohydr Polym. 2023;307:120611. DOI:10.1016/j.carbpol.2023.120611
31. Sun SF, Hsu CW, Lin HS, et al. Comparison of Single Intra-Articular Injection of Novel Hyaluronan (HYA-JOINT Plus) with Synvisc-One for Knee Osteoarthritis: A Randomized, Controlled, Double-Blind Trial of Efficacy and Safety. J Bone Joint Surg Am. 2017;99(6):462-71. DOI:10.2106/JBJS.16.00469
32. Ko PY, Li CY, Li CL, et al. Single Injection of Cross-Linked Hyaluronate in Knee Osteoarthritis: A 52-Week Double-Blind Randomized Controlled Trial. Pharmaceutics. 2022;14(9):1783. DOI:10.3390/pharmaceutics14091783
33. De Marziani L, Boffa A, Orazi S, et al. Joint Response to Exercise Is Affected by Knee Osteoarthritis: An Infrared Thermography Analysis. J Clin Med. 2023;12(10):3399. DOI:10.3390/jcm12103399
34. Vannini F, Spalding T, Andriolo L, et al. Sport and early osteoarthritis: the role of sport in aetiology, progression and treatment of knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2016;24(6):1786-96. DOI:10.1007/s00167-016-4090-5
35. De Marziani L, Sangiorgio A, Bensa A, et al. Intra-articular injections in sport-active patients with degenerative cartilage lesions or osteoarthritis of the knee: a systematic review. J Exp Orthop. 2023;10(1):112. DOI:10.1186/s40634-023-00674-0
36. Altman R, Lim S, Steen RG, Dasa V. Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database. PLoS One. 2015;10(12):e0145776. DOI:10.1371/journal.pone.0145776
37. Altman R, Fredericson M, Bhattacharyya SK, et al. Association between Hyaluronic Acid Injections and Time-to-Total Knee Replacement Surgery. J Knee Surg. 2016;29(7):564-70. DOI:10.1055/s-0035-1568992
38. Skou ST, Roos EM, Laursen MB, et al. A Randomized, Controlled Trial of Total Knee Replacement. N Engl J Med. 2015;373(17):1597-606. DOI:10.1056/NEJMoa1505467
39. Rahman A, Abid Hasan HM, Ali R, et al. Impact of Obesity on Joint Replacement Surgery Outcomes: A Comparative Study. Cureus. 2025;17(3):e80623. DOI:10.7759/cureus.80623
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41. Panunzi S, Maltese S, De Gaetano A, et al. Comparative efficacy of different weight loss treatments on knee osteoarthritis: A network meta-analysis. Obes Rev. 2021;22(8):e13230. DOI:10.1111/obr.13230
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Авторы

О.В. Теплякова*^1,2, А.В. Жиляков¹

¹ФГБОУ ВО «Уральский государственный медицинский университет» Минздрава России, Екатеринбург, Российская Федерация
²ООО «Медицинское объединение "Новая больница"», Екатеринбург, Российская Федерация
*oteplyakova69@gmail.com

________________________________________________

Olga V. Teplyakova*^1,2, Andrey V. Zhilyakov¹

¹Ural State Medical University, Ekaterinburg, Russian Federation
²Medical Association «New Hospital», Ekaterinburg, Russian Federation
*oteplyakova69@gmail.com

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