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Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial

  • Arthroscopy and Sports Medicine
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Introduction

The primary purposes of this study were to prove the efficacy of PRP injection therapy on knee pain and functions by comparing patients with mild to moderate OA with a placebo control group, and also to understand the effectiveness of multiple doses compared to a single dose. It was hypothesized that PRP would lead to more favorable results than the placebo at 1, 3, 6, 12 and 24 months after treatment.

Materials and methods

237 patients diagnosed with OA were randomly separated into 4 groups, who were administered the following: single dose of PRP (n: 62), single dose of sodium saline (NS) (n: 59), three doses of PRP (n: 63), and three doses of NS (n: 53). Clinical evaluations were made pre-treatment and at 1, 3, 6, 12 and 24 months post-treatment, using the Knee Injury and Osteoarthritis Result Score (KOOS), Kujala Patellofemoral Score, knee joint range of motion (ROM), measurements of knee circumference (KC), and mechanical axis angle (MAA) and a Visual Analog Scale (VAS) for the evaluation of pain.

Results

The better score values in the groups were recorded at 3 and 6 months. Patients treated with PRP maintained better scores at 3, 6 and 12 months compared to the NS groups (p < 0.05). Multiple doses of PRP were seen to be more effective than single-dose PRP at 6 and 12 months (p < 0.05). At the end of 24 months, there was no significant score difference across all the groups. The most positive change in scores was found in stage 2 OA, and the most positive change in ROM was in stage 3 OA patients. In the PRP groups, KC decreased more at 1 and 6 months (p < 0.05). Compared to other age groups, patients aged 51–65 years scored better at 6 months (p < 0.05). A negative correlation was determined with MAA scores (r = − 0.508, p < 0.001).

Conclusion

In comparison to the placebo (NS), leukocyte-rich PRP treatment was determined to be effective in the treatment of OA. Multiple doses of PRP increase the treatment efficacy and duration. Of all the patients treated with PRP, the best results were obtained by patients aged 51–65 years, with lower MAA, and by K/L stage 2 OA patients.

Study design

Randomized controlled trial; Level of evidence, 1.

Registration

NCT04454164 (ClinicalTrials.gov identifier).

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If requested, all data can be transmitted to the journal.

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References

  1. Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11:529–543

    Article  CAS  PubMed  Google Scholar 

  2. Goldring MB (2000) The role of the chondrocyte in osteoarthritis. Arthritis Rheum 43(9):1916–1926

    Article  CAS  PubMed  Google Scholar 

  3. Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE (2006) The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res Ther 8(6):R187

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Martel-Pelletier J, Boileau C, Pelletier JP, Roughley PJ (2008) Cartilage in normal and osteoarthritis conditions. Best Pract Res Clin Rheumatol 22(2):351–384

    Article  CAS  PubMed  Google Scholar 

  5. Gobbi A, Bathan L (2009) Biological approaches for cartilage repair. J Knee Surg 22(1):36–44

    Article  PubMed  Google Scholar 

  6. Grimaud E, Heymann D, Redini F (2002) Recent advances in TGF-beta effects on chondrocyte metabolism. Potential therapeutic roles of TGF-beta in cartilage disorders. Cytokine Growth Factor Rev 13(3):241–257

    Article  CAS  PubMed  Google Scholar 

  7. Mascarenhas R, Saltzman BM, Fortier LA, Cole BJ (2015) Role of platelet-rich plasma in articular cartilage injury and disease. J Knee Surg 28(1):3–10

    Article  PubMed  Google Scholar 

  8. Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA (2009) Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med 37(11):2259–2272

    Article  PubMed  Google Scholar 

  9. Kabiri A, Esfandiari E, Esmaeili A, Hashemibeni B, Pourazar A, Mardani M (2014) Platelet-rich plasma application in chondrogenesis. Adv Biomed Res 3:138

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Marques LF, Stessuk T, Camargo IC, Sabeh Junior N, dos Santos L, Ribeiro-Paes JT (2015) Platelet-rich plasma (PRP): methodological aspects and clinical applications. Platelets 26(2):101–113

    Article  CAS  PubMed  Google Scholar 

  11. Bannuru RR, Osani MC, Vaysbrot EE et al (2019) OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil 27(11):1578–1589

    Article  CAS  Google Scholar 

  12. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M (2008) Growth factors and cytokines in wound healing. Wound Repair Regen 16(5):585–601

    Article  PubMed  Google Scholar 

  13. Fortier LA, Barker JU, Strauss EJ, McCarrel TM, Cole BJ (2011) The role of growth factors in cartilage repair. Clin Orthop Relat Res 469(10):2706–2715

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH (2019) 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 Controll Clin Trial Arthrosc 35(1):106–117

    Google Scholar 

  15. Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A (2013) Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med 41(2):356–364

    Article  PubMed  Google Scholar 

  16. Wu YT, Hsu KC, Li TY, Chang CK, Chen LC (2018) Effects of platelet-rich plasma on pain and muscle strength in patients with knee osteoarthritis. Am J Phys Med Rehabil 97(4):248–254

    Article  PubMed  Google Scholar 

  17. Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC (2020) Platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Am. J. Sports Med 49:249–260

    Article  PubMed  Google Scholar 

  18. Filardo G, Kon E, Buda R et al (2011) Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc 19(4):528–535

    Article  PubMed  Google Scholar 

  19. Filardo G, Previtali D, Napoli F, Candrian C, Zaffagnini S, Grassi A (2020) PRP injections for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Cartilage. https://doi.org/10.1177/1947603520931170

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gormeli G, Gormeli CA, Ataoglu B, Colak C, Aslanturk O, Ertem K (2017) Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc 25(3):958–965

    Article  PubMed  Google Scholar 

  21. Kon E, Buda R, Filardo G et al (2010) Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 18(4):472–479

    Article  PubMed  Google Scholar 

  22. Kon E, Mandelbaum B, Buda R et al (2011) Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy 27(11):1490–1501

    Article  PubMed  Google Scholar 

  23. Migliorini F, Driessen A, Quack V et al (2020) Comparison between intra-articular infiltrations of placebo, steroids, hyaluronic and PRP for knee osteoarthritis: a Bayesian network meta-analysis. Orthop Trauma Surg Arch. https://doi.org/10.1007/s00402-020-03551-y

    Article  Google Scholar 

  24. Park YB, Kim JH, Ha CW, Lee DH (2021) Clinical efficacy of platelet-rich plasma injection and its association with growth factors in the treatment of mild to moderate knee osteoarthritis: a randomized double-blind controlled clinical trial as compared with hyaluronic acid. Am J Sports Med 49(2):487–496

    Article  PubMed  Google Scholar 

  25. Sampson S, Reed M, Silvers H, Meng M, Mandelbaum B (2010) Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: a pilot study. Am J Phys Med Rehabil 89(12):961–969

    Article  PubMed  Google Scholar 

  26. Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA (2017) 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 45(2):339–346

    Article  PubMed  Google Scholar 

  27. Di Martino A, Di Matteo B, Papio T et al (2019) 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 47(2):347–354

    Article  PubMed  Google Scholar 

  28. Filardo G, Di Matteo B, Di Martino A et al (2015) Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med 43(7):1575–1582

    Article  PubMed  Google Scholar 

  29. Olesen ML, Christensen BB, Foldager CB, Hede KC, Bergholt NL, Lind M (2020) No effect of platelet-rich plasma as adjuvant to bone marrow stimulation for the treatment of chondral defects in a large animal model. Arch Orthop Trauma Surg 140(1):77–84

    Article  PubMed  Google Scholar 

  30. Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD (2016) Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy 32(3):495–505

    Article  PubMed  Google Scholar 

  31. Nguyen RT, Borg-Stein J, McInnis K (2011) Applications of platelet-rich plasma in musculoskeletal and sports medicine: an evidence-based approach. PMR 3(3):226–250

    Article  Google Scholar 

  32. Altman R, Asch E, Bloch D et al (1986) 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 29(8):1039–1049

    Article  CAS  PubMed  Google Scholar 

  33. Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16(4):494–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT (2004) Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 91(1):4–15

    Article  CAS  PubMed  Google Scholar 

  35. Mishra A, Harmon K, Woodall J, Vieira A (2012) Sports medicine applications of platelet rich plasma. Curr Pharm Biotechnol 13(7):1185–1195

    Article  CAS  PubMed  Google Scholar 

  36. Jang SJ, Kim JD, Cha SS (2013) Platelet-rich plasma (PRP) injections as an effective treatment for early osteoarthritis. Eur J Orthop Surg Traumatol 23(5):573–580

    Article  PubMed  Google Scholar 

  37. Smith PA (2016) Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee osteoarthritis: an FDA-sanctioned, randomized, double-blind, placebo-controlled clinical trial. Am J Sports Med 44(4):884–891

    Article  PubMed  Google Scholar 

  38. Ghai B, Gupta V, Jain A, Goel N, Chouhan D, Batra YK (2019) Effectiveness of platelet rich plasma in pain management of osteoarthritis knee: double blind, randomized comparative study. Rev Bras Anestesiol 69(5):439–447

    Article  Google Scholar 

  39. Kaux JF, Le Goff C, Seidel L et al (2011) Comparative study of five techniques of preparation of platelet-rich plasma. Pathol Biol (Paris) 59(3):157–160

    Article  Google Scholar 

  40. Marx RE (2001) Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent 10(4):225–228

    Article  CAS  PubMed  Google Scholar 

  41. Raeissadat SA, Ghorbani E, Sanei Taheri M et al (2020) MRI changes after platelet rich plasma injection in knee osteoarthritis (randomized clinical trial). J Pain Res 13:65–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gobbi A, Lad D, Karnatzikos G (2015) The effects of repeated intra-articular PRP injections on clinical outcomes of early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 23(8):2170–2177

    Article  PubMed  Google Scholar 

  43. Simental-Mendia M, Acosta-Olivo CA, Hernandez-Rodriguez AN et al (2019) Intraarticular injection of platelet-rich plasma in knee osteoarthritis: single versus triple application approach. Pilot study Acta Reumatol Port 44(2):138–144

    PubMed  Google Scholar 

  44. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F (2010) Biological, clinical, and ethical advances of placebo effects. Lancet 375(9715):686–695

    Article  PubMed  PubMed Central  Google Scholar 

  45. Raeissadat SA, Rayegani SM, Hassanabadi H et al (2015) Knee osteoarthritis injection choices: platelet-rich plasma (PRP) versus hyaluronic acid (a one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord 8:1–8

    Article  PubMed  PubMed Central  Google Scholar 

  46. Taniguchi Y, Yoshioka T, Sugaya H et al (2019) Growth factor levels in leukocyte-poor platelet-rich plasma and correlations with donor age, gender, and platelets in the Japanese population. J Exp Orthop 6(1):4

    Article  PubMed  PubMed Central  Google Scholar 

  47. Evanson JR, Guyton MK, Oliver DL et al (2014) Gender and age differences in growth factor concentrations from platelet-rich plasma in adults. Mil Med 179(7):799–805

    Article  PubMed  Google Scholar 

  48. Rahmati M, Nalesso G, Mobasheri A, Mozafari M (2017) Aging and osteoarthritis: central role of the extracellular matrix. Ageing Res Rev 40:20–30

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Babbush CA, Kevy SV, Jacobson MS (2003) An in vitro and in vivo evaluation of autologous platelet concentrate in oral reconstruction. Implant Dent 12(1):24–34

    Article  PubMed  Google Scholar 

  51. Cerejo R, Dunlop DD, Cahue S, Channin D, Song J, Sharma L (2002) The influence of alignment on risk of knee osteoarthritis progression according to baseline stage of disease. Arthritis Rheum 46(10):2632–2636

    Article  PubMed  Google Scholar 

  52. Sharma L, Song J, Felson DT, Cahue S, Shamiyeh E, Dunlop DD (2001) The role of knee alignment in disease progression and functional decline in knee osteoarthritis. JAMA 286(2):188–195

    Article  CAS  PubMed  Google Scholar 

  53. Brouwer GM, van Tol AW, Bergink AP et al (2007) Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee. Arthritis Rheum 56(4):1204–1211

    Article  CAS  PubMed  Google Scholar 

  54. Cicuttini F, Wluka A, Hankin J, Wang Y (2004) Longitudinal study of the relationship between knee angle and tibiofemoral cartilage volume in subjects with knee osteoarthritis. Rheumatol (Oxf) 43(3):321–324

    Article  CAS  Google Scholar 

  55. Felson DT, Niu J, Gross KD et al (2013) Valgus malalignment is a risk factor for lateral knee osteoarthritis incidence and progression: findings from the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative. Arthritis Rheum 65(2):355–362

    Article  PubMed  PubMed Central  Google Scholar 

  56. Sharma L, Song J, Dunlop D et al (2010) Varus and valgus alignment and incident and progressive knee osteoarthritis. Ann Rheum Dis 69(11):1940–1945

    Article  PubMed  Google Scholar 

  57. Lisi C, Perotti C, Scudeller L et al (2018) Treatment of knee osteoarthritis: platelet-derived growth factors vs. hyaluronic acid: a randomized controlled trial. Clin Rehabil 32(3):330–339

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank M. D. Giuseppe Filardo, who shared his knowledge and experiences with us in determining the study subject and in the different stages of the study preparation process. We would like to thank M. D. Leman TOMAK for her contributions in data analysis stages.

Funding

No funding was received for conducting this study.

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Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by AY, FS, HÇ and AE. The first draft of the manuscript was written by AY and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Alparslan Yurtbay.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

This prospective, randomized, placebo-controlled, double-blind study was conducted with the approval of the Republic of Turkey Ministry of Health, General Directorate of Health Services, Department of Blood, Organ and Tissue Transplant Services, Root Transplants Scientific Advisory Commission (Approval number: 56733164/203). All the details of this clinical study were explained to the patients, and all participated in the study voluntarily, providing written informed consent. All the study procedures complied with the principles of the Declaration of Helsinki.

Consent to participate

The informed consent form, permission to participate in this clinical study and the publication of the data of this study in any journal were obtained from all participants included in this study.

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Yurtbay, A., Say, F., Çinka, H. et al. Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial. Arch Orthop Trauma Surg 142, 2755–2768 (2022). https://doi.org/10.1007/s00402-021-04230-2

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