Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial

Giuseppe Filardo, Elizaveta Kon, Alessandro Di Martino, Berardo Di Matteo, Maria Letizia Merli, Annarita Cenacchi, Pier Maria Fornasari, Maurilio Marcacci, Giuseppe Filardo, Elizaveta Kon, Alessandro Di Martino, Berardo Di Matteo, Maria Letizia Merli, Annarita Cenacchi, Pier Maria Fornasari, Maurilio Marcacci

Abstract

Background: Platelet rich plasma (PRP), a blood-derived product rich in growth factors, is a promising treatment for cartilage defects but there is still a lack of clinical evidence. The aim of this study is to show, through a randomized double blind prospective trial, the efficacy of this procedure, by comparing PRP to Hyaluronic Acid (HA) injections for the treatment of knee chondropathy or osteoarthritis (OA).

Methods: 109 patients (55 treated with HA and 54 with PRP) were treated and evaluated at 12 months of follow-up. The patients were enrolled according to the following inclusion criteria: age > 18 years, history of chronic (at least 4 months) pain or swelling of the knee and imaging findings of degenerative changes of the joint (Kellgren-Lawrence Score up to 3). A cycle of 3 weekly injections was administered blindly. All patients were prospectively evaluated before and at 2, 6, and 12 months after the treatment by: IKDC, EQ-VAS, TEGNER, and KOOS scores. Range of motion and knee circumference changes were measured over time. Adverse events and patient satisfaction were also recorded.

Results: Only minor adverse events were detected in some patients, such as mild pain and effusion after the injections, in particular in the PRP group, where a significantly higher post-injective pain reaction was observed (p=0.039). At the follow-up evaluations, both groups presented a clinical improvement but the comparison between the two groups showed a not statistically significant difference in all scores evaluated. A trend favorable for the PRP group was only found in patients with low grade articular degeneration (Kellgren-Lawrence score up to 2).

Conclusions: Results suggest that PRP injections offer a significant clinical improvement up to one year of follow-up. However, conversely to what was shown by the current literature, for middle-aged patients with moderate signs of OA, PRP results were not better than those obtained with HA injections, and thus it should not be considered as first line treatment. More promising results are shown for its use in low grade degeneration, but they still have to be confirmed.

Figures

Figure 1
Figure 1
IKDC subjective score in both PRP and HA treatment groups before and at 2, 6, and 12 months after treatment. No statistical inter-group difference was observed.
Figure 2
Figure 2
IKDC subjective results obtained with PRP and HA treatments in two patient subgroups: patients affected by Kellgren Lawrence grade 0-II lesions and patients presenting grade III level of knee degeneration.
Figure 3
Figure 3
IKDC subjective improvement from basal level to 2, 6, and 12 months of follow-up after treatment with PRP or HA injections in low grade cartilage degenerative pathology. A tendency towards better results for PRP in this patient category is observed at both 6 and 12 months: p = 0.08 and p = 0.07, respectively.

References

    1. Curl WW, Krome J, Gordon ES, Rushing J, Smith BP, Poehling GG. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy. 1997;13(4):456–460. doi: 10.1016/S0749-8063(97)90124-9.
    1. Widuchowski W, Widuchowski J, Trzaska T. Articular cartilage defects: study of 25,124 knee arthroscopies. Knee. 2007;14:177–182. doi: 10.1016/j.knee.2007.02.001.
    1. Luyten FP, Denti M, Filardo G, Kon E, Engebretsen L. Definition and classification of early osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2012;20(3):401–406. doi: 10.1007/s00167-011-1743-2.
    1. Kon E, Filardo G, Drobnic M, Madry H, Jelic M, van Dijk N, Della Villa S. Non-surgical management of early knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012;20(3):436–449. doi: 10.1007/s00167-011-1713-8.
    1. Gomoll AH, Filardo G, de Girolamo L, Esprequeira-Mendes J, Marcacci M, Rodkey WG, Steadman RJ, Zaffagnini S, Kon E. Surgical treatment for early osteoarthritis. Part I: cartilage repair procedures. Knee Surg Sports Traumatol Arthrosc. 2012;20(3):450–466. doi: 10.1007/s00167-011-1780-x.
    1. Gomoll AH, Filardo G, Almqvist FK, Bugbee WD, Jelic M, Monllau JC, Puddu G, Rodkey WG, Verdonk P, Verdonk R, Zaffagnini S, Marcacci M. Surgical treatment for early osteoarthritis. Part II: allografts and concurrent procedures. Knee Surg Sports Traumatol Arthrosc. 2012;20(3):468–486. doi: 10.1007/s00167-011-1714-7.
    1. Kon E, Filardo G, Di Martino A, Marcacci M. Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use. Knee Surg Sports Traumatol Arthrosc. 2011;19(4):516–527. doi: 10.1007/s00167-010-1306-y.
    1. Gobbi A, Bathan L. Biological approaches for cartilage repair. J Knee Surg. 2009;22(1):36–44. doi: 10.1055/s-0030-1247726.
    1. Grimaud E, Heymann D, Rédini F. Recent advances in TGF-beta effects on chondrocyte metabolism. Potential therapeutic roles of TGF-beta in cartilage disorders. Cytokine Growth Factor Rev. 2002;13(3):241–257. doi: 10.1016/S1359-6101(02)00004-7.
    1. Cole BJ, Seroyer ST, Filardo G, Bajaj S, Fortier LA. Platelet-rich plasma: where are we now and where are we going? Sports Health. 2010;2(3):203–210. doi: 10.1177/1941738110366385.
    1. Tschon M, Fini M, Giardino R, Filardo G, Dallari D, Torricelli P, Martini L, Giavaresi G, Kon E, Maltarello MC, Nicolini A, Carpi A. Lights and shadows concerning platelet products for musculoskeletal regeneration. Front Biosci (Elite Ed) 2011;3:96–107. doi: 10.2741/e224.
    1. Filardo G, Kon E. PRP: more words than facts. Knee Surg Sports Traumatol Arthrosc. 2012;20(9):1655–1656. doi: 10.1007/s00167-012-2136-x.
    1. Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med. 2009;37(11):2259–2272. doi: 10.1177/0363546509349921.
    1. Sanchez AR, Sheridan PJ, Kupp LI. Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral Maxillofac Implants. 2003;18:93–103.
    1. Mishra A, Woodall J Jr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med. 2009;28(1):113–125. doi: 10.1016/j.csm.2008.08.007.
    1. Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Tromb Haemost. 2004;91:4–15.
    1. Senet P, Bon FX, Benbunan M, Bussel A, Traineau R, Calvo F, Dubertret L, Dosquet C. Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers. J Vasc Surg. 2003;38:1342–1348. doi: 10.1016/S0741-5214(03)00908-X.
    1. Torricelli P, Fini M, Filardo G, Tschon M, Pischedda M, Pacorini A, Kon E, Giardino R. Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses. Int Orthop. 2011;35(10):1569–1576. doi: 10.1007/s00264-011-1237-3.
    1. Marx R. Platelet rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 2001;10:225–228. doi: 10.1097/00008505-200110000-00002.
    1. Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surgery. 2004;62:489–496. doi: 10.1016/j.joms.2003.12.003.
    1. Creaney L, Hamilton B. Growth factor delivery methods in the management of sports injuries: the state of play. Br J Sports Med. 2008;42(5):314–320. doi: 10.1136/bjsm.2007.040071.
    1. Sánchez M, Anitua E, Azofra J, Andía I, Padilla S, Mujika I. Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices. Am J Sports Med. 2007;35(2):245–251.
    1. Colen S, van den Bekerom MP, Mulier M, Haverkamp D. Hyaluronic acid in the treatment of knee osteoarthritis: a systematic review and meta-analysis with emphasis on the efficacy of different products. BioDrugs. 2012;26(4):257–268. doi: 10.2165/11632580-000000000-00000.
    1. Sánchez M, Azofra J, Anitua E, Andía I, Padilla S, Santisteban J, Mujika I. Plasma rich in growth factors to treat an articular cartilage avulsion: a case report. Med Sci Sports Exerc. 2003;35(10):1648–1652. doi: 10.1249/01.MSS.0000089344.44434.50.
    1. Sánchez M, Anitua E, Azofra J, Aguirre JJ, Andia I. Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. Clin Exp Rheumatol. 2008;26(5):910–913.
    1. Sampson S, Reed M, Silvers H, Meng M, Mandelbaum B. Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: a pilot study. Am J Phys Med Rehabil. 2010;89(12):961–969. doi: 10.1097/PHM.0b013e3181fc7edf.
    1. Wang-Saegusa A, Cugat R, Ares O, Seijas R, Cuscó X, Garcia-Balletbó M. Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life. Arch Orthop Trauma Surg. 2011;131(3):311–317. doi: 10.1007/s00402-010-1167-3.
    1. Napolitano M, Matera S, Bossio M, Crescibene A, Costabile E, Almolla J, Almolla H, Togo F, Giannuzzi C, Guido G. Autologous platelet gel for tissue regeneration in degenerative disorders of the knee. Blood Transfus. 2012;10(1):72–77.
    1. Gobbi A, Karnatzikos G, Mahajan V, Malchira S. Platelet-rich Plasma treatment in symptomatic patients with knee Osteoarthritis: Preliminary results in a group of active patients. Sports Health. 2012;4:162–172. doi: 10.1177/1941738111431801.
    1. Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A. 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.
    1. Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Cenacchi A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):472–479. doi: 10.1007/s00167-009-0940-8.
    1. Filardo G, Kon E, Buda R, Timoncini A, Di Martino A, Cenacchi A, Fornasari PM, Giannini S, Marcacci M. 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.
    1. Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy. 2011;27(11):1490–1501. doi: 10.1016/j.arthro.2011.05.011.
    1. Filardo G, Kon E, Pereira Ruiz MT, Vaccaro F, Guitaldi R, Di Martino A, Cenacchi A, Fornasari PM, Marcacci M. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012;20(10):2078–2087.
    1. Sánchez M, Fiz N, Azofra J, Usabiaga J, Aduriz Recalde E, Garcia Gutierrez A, Albillos J, Gárate R, Aguirre JJ, Padilla S, Orive G, Anitua E. A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy. 2012;28(8):1070–1078. doi: 10.1016/j.arthro.2012.05.011.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe