Сравнительный анализ эффективности применения обогащенной тромбоцитами плазмы и гиалуронатов при лечении остеоартрита коленного сустава: метаанализ исследований с шестимесячным наблюдением

Введение. В научной литературе представлено множество исследований, сравнивающих эффективность применения PRP-терапии, или обогащенной тромбоцитами плазмы (ОТП), и препаратов гиалуроновой кислоты (ГК) при остеоартрите коленного сустава, однако результаты носят противоречивый характер из-за методологических ограничений и высокой неоднородности протоколов лечения.

Цель работы — сравнить данные научных исследований об эффективности применения ОТП и препаратов ГК средней молекулярной массы в лечении больных остеоартритом коленного сустава.

Материалы и методы. Проведен поиск рандомизированных контролируемых исследований в базах PubMed, Embase и Cochrane Library за 2017–2024 гг. по следующим ключевым словам: osteoarthritis, knee joint, intra-articular injections, platelet-rich plasma, hyaluronic acid, WOMAC, meta-analysis. Включены исследования, в которых рассматривали пациентов с диагнозом «остеоартрит коленного сустава» любой степени тяжести, получавших внутрисуставные инъекции ОТП или ГК с оценкой выраженности болевого синдрома по шкале WOMAC. После строгого отбора включены четыре исследования с идентичными протоколами лечения.

Результаты. В метаанализ включены данные 333 пациентов (164 в группе ОТП и 169 в группе ГК). Средний балл выраженности болевого синдрома по WOMAC через шесть месяцев от начала лечения (внутрисуставное введение) составил 4,52 (SD = 1,59) в группе ОТП и 4,95 (SD = 2,07) в группе ГК. Размер эффекта Hedges'g: 0,26 (95 % ДИ: –0,61–1,14; p = 0,336). Публикационное смещение отсутствовало (тест Эггера, p = 0,06).

Обсуждение. В результате нашего исследования значимых различий между применением ОТП и ГК не выявлено, что противоречит ряду предыдущих метаанализов. Возможно, данный факт обусловлен использованием при нашем анализе более строгих критериев включения и оценкой препаратов ГК только средней молекулярной массы.

Заключение. Проведенный метаанализ, направленный на сравнительную оценку эффективности применения ОТП и ГК средней молекулярной массы при лечении пациентов с остеоартритом коленного сустава, не выявил статистически значимых различий между группами при оценке выраженности болевого синдрома по шкале WOMAC через шесть месяцев от начала лечения, что свидетельствует о сопоставимой эффективности данных методов терапии.

1. Wang MN, Liu L, Zhao LP, et al. Research of inflammatory factors and signaling pathways in knee osteoarthritis. Zhongguo Gu Shang. 2020;33(4):388-392. (In Chin.) doi: 10.12200/j.issn.1003-0034.2020.04.020.

2. Миронов С.П., Омельяненко Н.П., Орлецкий А.К. и др. Остеоартроз: современное состояние проблемы (аналитический обзор). Вестник травматологии и ортопедии им. Н.Н. Приорова. 2001;8(2):96-99. doi: 10.17816/vto98472.

3. Conrozier T. How to Treat Osteoarthritis in Obese Patients? Curr Rheumatol Rev. 2020;16(2):99-104. doi: 10.2174/1573397115666190625105759.

4. Andia I, Abate M. Knee osteoarthritis: Hyaluronic acid, platelet-rich plasma or both in association? Expert Opin Biol Ther. 2014;14(5):635-649. doi: 10.1517/14712598.2014.889677.

5. Saito T, Tanaka S. Molecular mechanisms underlying osteoarthritis development: Notch and NF-κB. Arthritis Res Ther. 2017;19(1):94. doi: 10.1186/s13075-017-1296-y.

6. Wang M, Shen J, Jin H, et al. Recent progress in understanding molecular mechanisms of cartilage degeneration during osteoarthritis. Ann N Y Acad Sci. 2011;1240:61-69. doi: 10.1111/j.1749-6632.2011.06258.x.

7. Lisi C, Perotti C, Scudeller L, et al. Treatment of knee osteoarthritis: platelet-derived growth factors vs. hyaluronic acid. A randomized controlled trial. Clin Rehabil. 2018;32(3):330-339. doi: 10.1177/0269215517724193.

8. Papalia R, Zampogna B, Russo F, et al. Comparing hybrid hyaluronic acid with PRP in end career athletes with degenerative cartilage lesions of the knee. J Biol Regul Homeost Agents. 2016;30(4 Suppl 1):17-23.

9. Raeissadat SA, Ghazi Hosseini P, Bahrami MH, et al. The comparison effects of intra-articular injection of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factor (PRGF), Hyaluronic Acid (HA), and ozone in knee osteoarthritis; a one year randomized clinical trial. BMC Musculoskelet Disord. 2021;22(1):134. doi: 10.1186/s12891-021-04017-x.

10. Filardo G, Kon E, Buda R, et al. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2011;19(4):528-535. doi: 10.1007/s00167-010-1238-6.

11. Spaková T, Rosocha J, Lacko M, et al. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil. 2012;91(5):411-417. doi: 10.1097/PHM.0b013e3182aab72.

12. Filardo G, Kon E, Di Martino A, et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord. 2012;13:229. doi: 10.1186/1471-2474-13-229.

13. Laudy AB, Bakker EW, Rekers M, Moen MH. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. 2015;49(10):657-672. doi: 10.1136/bjsports-2014-094036.

14. Dai WL, Zhou AG, Zhang H, Zhang J. Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials. Arthroscopy. 2017;33(3):659-670.e1. doi: 10.1016/j.arthro.2016.09.024.

15. Gaonkar K, Gaonkar N, Gupta K, et al. Role of arthroscopy in osteoarthritis of the knee joint. Int J Clin Trials. 2015;421(3):42-49. doi: 10.5455/2349-3259.ijct20150503.

16. Zaripova L, Tazhibayeva D, Kabdualieva N, et al. Osteoarthritis: A contemporary view of the problem, the possibilities of therapy and prospects for further research. J Clin Med Kaz. 2022;19(6):6-12. doi: 10.23950/jcmk/12629.

17. Eymard F, Ornetti P, Maillet J, et al. Intra-articular injections of platelet-rich plasma in symptomatic knee osteoarthritis: a consensus statement from French-speaking experts. Knee Surg Sports Traumatol Arthrosc. 2021;29(10):3195-3210. doi: 10.1007/s00167-020-06102-5.

18. Gilat R, Haunschild ED, Knapik DM, et al. Hyaluronic acid and platelet-rich plasma for the management of knee osteoarthritis. Int Orthop. 2021;45(2):345-354. doi: 10.1007/s00264-020-04801-9.

19. Raeissadat SA, Ghorbani E, Sanei Taheri M, et al. MRI Changes After Platelet Rich Plasma Injection in Knee Osteoarthritis (Randomized Clinical Trial). J Pain Res. 2020;13:65-73. doi: 10.2147/JPR.S204788.

20. Duymus TM, Mutlu S, Dernek B, et al. Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options. Knee Surg Sports Traumatol Arthrosc. 2017;25(2):485-492. doi: 10.1007/s00167-016-4110-5.

21. Su K, Bai Y, Wang J, et al. Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous PRP injections to treat patients with knee osteoarthritis. Clin Rheumatol. 2018;37(5):1341-1350. doi: 10.1007/s10067-018-3985-6.

22. Wang YC, Lee CL, Chen YJ, et al. Comparing the Efficacy of Intra-Articular Single Platelet-Rich Plasma(PRP) versus Novel Crosslinked Hyaluronic Acid for Early-Stage Knee Osteoarthritis: A Prospective, Double-Blind, Randomized Controlled Trial. Medicina (Kaunas). 2022;58(8):1028. doi: 10.3390/medicina58081028.

23. Cole BJ, Karas V, Hussey K, et al. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. Am J Sports Med. 2017;45(2):339-346. doi: 10.1177/0363546516665809.

24. Lu M, Jin Y. Efficacy Evaluation of the Combined Platelet-Rich Plasma and Hyaluronic Acid after Arthroscopic Joint Debridement in Treating Knee Osteoarthritis. Scanning. 2022;2022:6994017. doi: 10.1155/2022/6994017.

25. Louis ML, Magalon J, Jouve E, et al. Growth Factors Levels Determine Efficacy of Platelets Rich Plasma Injection in Knee Osteoarthritis: A Randomized Double Blind Noninferiority Trial Compared With Viscosupplementation. Arthroscopy. 2018;34(5):1530-1540.e2. doi: 10.1016/j.arthro.2017.11.035.

26. Zhao J, Huang H, Liang G, et al. Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2020;21(1):224. doi: 10.1186/s12891-020-03262-w.

27. Filardo G, Previtali D, Napoli F, et al. PRP Injections for the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials. Cartilage. 2021;13(1_suppl):364S-375S. doi: 10.1177/1947603520931170.

28. Barakat AS, Ibrahim NM, Elghobashy O, et al. Prevention of post-traumatic osteoarthritis after intra-articular knee fractures using hyaluronic acid: a randomized prospective pilot study. Int Orthop. 2019;43(11):2437-2445. doi: 10.1007/s00264-019-04360-8.

29. de Sire A, Stagno D, Minetto MA, et al. Long-term effects of intra-articular oxygen-ozone therapy versus hyaluronic acid in older people affected by knee osteoarthritis: A randomized single-blind extension study. J Back Musculoskelet Rehabil. 2020;33(3):347-354. doi: 10.3233/BMR-181294.

30. Li M, Huang Z, Wang S, et al. Intra-articular injections of platelet-rich plasma vs. hyaluronic acid in patients with knee osteoarthritis: Preliminary follow-up results at 6-months. Exp Ther Med. 2021;21(6):598. doi: 10.3892/etm.2021.10030.

31. Desai MJ, Safriel Y. MRI for in vivo Analysis of Ablation Zones Formed by Cooled Radiofrequency Neurotomy to Treat Chronic Joint Pain Across Multiple Axial Spine Sites. J Pain Res. 2022;15:423-430. doi: 10.2147/JPR.S342795.

32. Suurmond R, van Rhee H, Hak T. Introduction, comparison, and validation of Meta-Essentials: A free and simple tool for meta-analysis. Res Synth Methods. 2017;8(4):537-553. doi: 10.1002/jrsm.1260.

33. Dwan K, Li T, Altman DG, Elbourne D. CONSORT 2010 statement: extension to randomised crossover trials. BMJ. 2019;366:l4378. doi: 10.1136/bmj.l4378.

34. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210. doi: 10.1186/s13643-016-0384-4.

35. Partan RU, Putra KM, Hafizzanovian H, et al. Clinical Outcome of Multiple Platelet-Rich Plasma Injection and Correlation with PDGF-BB in the Treatment of Knee Osteoarthritis. J Pers Med. 2024;14(2):183. doi: 10.3390/jpm14020183.

36. Assirelli E, Filardo G, Mariani E, et al. Effect of two different preparations of platelet-rich plasma on synoviocytes. Knee Surg Sports Traumatol Arthrosc. 2015;23(9):2690-2703. doi: 10.1007/s00167-014-3113-3.

37. Lin KY, Yang CC, Hsu CJ, et al. Intra-articular Injection of Platelet-Rich Plasma Is Superior to Hyaluronic Acid or Saline Solution in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized, Double-Blind, Triple-Parallel, Placebo-Controlled Clinical Trial. Arthroscopy. 2019;35(1):106-117. doi: 10.1016/j.arthro.2018.06.035.

38. 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.

39. Arden NK, Åkermark C, Andersson M, et al. A randomized saline-controlled trial of NASHA hyaluronic acid for knee osteoarthritis. Curr Med Res Opin. 2014;30(2):279-286. doi: 10.1185/03007995.2013.855631.

40. Di Martino A, Di Matteo B, Papio T, et al. Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial. Am J Sports Med. 2019;47(2):347-354. doi: 10.1177/0363546518814532.

41. Cortet B, Lombion S, Naissant B, et al. Non-Inferiority of a Single Injection of Sodium Hyaluronate Plus Sorbitol to Hylan G-F20: A 6-Month Randomized Controlled Trial. Adv Ther. 2021;38(5):2271-2283. doi: 10.1007/s12325-021-01648-3.

42. Conrozier T, Eymard F, Chouk M, Chevalier X. Impact of obesity, structural severity and their combination on the efficacy of viscosupplementation in patients with knee osteoarthritis. BMC Musculoskelet Disord. 2019;20(1):376. doi: 10.1186/s12891-019-2748-0.

43. Fernández-Ferro M, Fernández-Sanromán J, Blanco-Carrión A, et al. Comparison of intra-articular injection of plasma rich in growth factors versus hyaluronic acid following arthroscopy in the treatment of temporomandibular dysfunction: A randomised prospective study. J Craniomaxillofac Surg. 2017;45(4):449-454. doi: 10.1016/j.jcms.2017.01.010.

44. Anitua E, Sánchez M, Orive G, Andía I. The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials. 2007;28(31):4551-4560. doi: 10.1016/j.biomaterials.2007.06.037.

45. Simental-Mendía M, Vílchez-Cavazos JF, Peña-Martínez VM,et al. Leukocyte-poor platelet-rich plasma is more effective than the conventional therapy with acetaminophen for the treatment of early knee osteoarthritis. Arch Orthop Trauma Surg. 2016;136(12):1723-1732. doi: 10.1007/s00402-016-2545-2.

46. Riboh JC, Saltzman BM, Yanke AB, et al. Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis. Am J Sports Med. 2016;44(3):792-800. doi: 10.1177/0363546515580787.

47. Adams ME, Atkinson MH, Lussier AJ, et al. The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone. Osteoarthritis Cartilage. 1995;3(4):213-225. doi: 10.1016/s1063-4584(05)80013-5.

48. Altman RD, Rosen JE, Bloch DA, et al. A double-blind, randomized, saline-controlled study of the efficacy and safety of EUFLEXXA for treatment of painful osteoarthritis of the knee, with an open-label safety extension (the FLEXX trial). Semin Arthritis Rheum. 2009;39(1):1-9. doi: 10.1016/j.semarthrit.2009.04.001.

49. Sdeek M, Sabry D, El-Sdeek H, Darweash A. Intra-articular injection of Platelet rich plasma versus Hyaluronic acid for moderate knee osteoarthritis. A prospective, double-blind randomized controlled trial on 189 patients with follow-up for three years. Acta Orthop Belg. 2021;87(4):729-734. doi: 10.52628/87.4.18.

50. Saornil JV, Sánchez Milá Z, Campón Chekroun AM, et al. Comparative Study of the Efficacy of Hyaluronic Acid, Dry Needling and Combined Treatment in Patellar Osteoarthritis-Single-Blind Randomized Clinical Trial. Int J Environ Res Public Health. 2022;19(17):10912. doi: 10.3390/ijerph191710912.

51. Bettonville M, Léon M, Margaux J, et al. Safety and efficacy of a single intra-articular injection of a novel enhanced protein solution (JTA-004) compared to hylan G-F 20 in symptomatic knee osteoarthritis: a randomized, double-blind, controlled phase II/III study. BMC Musculoskelet Disord. 2021;22(1):888. doi: 10.1186/s12891-021-04750-3.

52. Conrozier T, Eymard F, Afif N, et al. Safety and efficacy of intra-articular injections of a combination of hyaluronic acid and mannitol (HAnOX-M) in patients with symptomatic knee osteoarthritis: Results of a double-blind, controlled, multicenter, randomized trial. Knee. 2016;23(5):842-848. doi: 10.1016/j.knee.2016.05.015.

53. Askari A, Gholami T, NaghiZadeh MM, et al. Hyaluronic acid compared with corticosteroid injections for the treatment of osteoarthritis of the knee: a randomized control trail. Springerplus. 2016;5:442. doi: 10.1186/s40064-016-2020-0.

54. Paterson KL, Nicholls M, Bennell KL, Bates D. Intra-articular injection of photo-activated platelet-rich plasma in patients with knee osteoarthritis: a double-blind, randomized controlled pilot study. BMC Musculoskelet Disord. 2016;17:67. doi: 10.1186/s12891-016-0920-3.

55. Bahrami MH, Raeissadat SA, Cheraghi M, et al. Efficacy of single high-molecular-weight versus triple low-molecular-weight hyaluronic acid intra-articular injection among knee osteoarthritis patients. BMC Musculoskelet Disord. 2020;21(1):550. doi: 10.1186/s12891-020-03577-8.

56. Campos ALS, E Albuquerque RSP, da Silva EB, et al. Viscosupplementation in patients with severe osteoarthritis of the knee: six month follow-up of a randomized, double-blind clinical trial. Int Orthop. 2017;41(11):2273-2280. doi: 10.1007/s00264-017-3625-9.

57. Farr J, Gomoll AH, Yanke AB, et al. A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. J Knee Surg. 2019;32(11):1143-1154. doi: 10.1055/s-0039-1696672.

58. Gobbi A, Morales M, Avio G, D’Ambrosi R. Double-blinded prospective randomized clinical trial in knee joint osteoarthritis treatment: safety assessment and performance of trehalose hyaluronic acid versus standard infiltrative therapy based on medium-weight sodium hyaluronate. J Cartil Joint Preserv. 2022;2(3):100043. doi: 10.1016/j.jcjp.2022.100043.

59. Goncars V, Jakobsons E, Blums K, et al. The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections. Medicina (Kaunas). 2017;53(2):101-108. doi: 10.1016/j.medici.2017.02.002.

60. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512-525. doi: 10.1093/ije/dyv080.

61. Almalik O, Zhan Z, van den Heuvel ER. Tests for publication bias are unreliable in case of heteroscedasticity. Contemp Clin Trials Commun. 2021;22:100781. doi: 10.1016/j.conctc.2021.100781.

62. Gjerdevik M, Heuch I. Improving the error rates of the Begg and Mazumdar test for publication bias in fixed effects meta-analysis. BMC Med Res Methodol. 2014;14:109. doi: 10.1186/1471-2288-14-109.

63. Shi L, Lin L. The trim-and-fill method for publication bias: practical guidelines and recommendations based on a large database of meta-analyses. Medicine (Baltimore). 2019;98(23):e15987. doi: 10.1097/MD.0000000000015987.

64. Peters JL, Sutton AJ, Jones DR, et ak. Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity. Stat Med. 2007;26(25):4544-4562. doi: 10.1002/sim.2889.

65. Crowther M, Lim W, Crowther MA. Systematic review and meta-analysis methodology. Blood. 2010;116(17):3140-3146. doi: 10.1182/blood-2010-05-280883.

66. Čehovin G, Bosnjak M, Lozar Manfreda K. Meta-Analyses in Survey Methodology: A Systematic Review. Public Opinion Quarterly. 2018;82(2):641-660. doi: 10.1093/poq/nfy042.

67. Miller LE. Towards reaching consensus on hyaluronic acid efficacy in knee osteoarthritis. Clin Rheumatol. 2019;38(10):2881-2883. doi: 10.1007/s10067-019-04597-z.

68. Raeissadat SA, Babaee M, Rayegani SM, et al. An overview of platelet products (PRP, PRGF, PRF, etc.) in the Iranian studies. Future Sci OA. 2017;3(4):FSO231. doi: 10.4155/fsoa-2017-0045.

69. Vannabouathong C, Bhandari M, Bedi A, 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. doi: 10.2106/JBJS.RVW.17.00167.

70. Filardo G, Kon E, Pereira Ruiz MT, et al. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single-versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012;20(10):2082-2091. doi: 10.1007/s00167-011-1837-x.

71. Yaradilmis YU, Demirkale I, Safa Tagral A, et al. Comparison of two platelet rich plasma formulations with viscosupplementation in treatment of moderate grade gonarthrosis: A prospective randomized controlled study. J Orthop. 2020;20:240-246. doi: 10.1016/j.jor.2020.01.041.

72. Третьяков А.А.,Зиновкин Д.А.,Карпенко Ф.Н. идр. Патоморфологическая оценка эффективности внутрисуставного применения растворимых факторов тромбоцитов для лечения экспериментального остеоартрита. Гений ортопедии. 2024;30(1):90-98. doi: 10.18019/1028-4427-2024-30-1-90-98.