Intra-articular injection of photo-activated platelet-rich plasma in patients with knee osteoarthritis: a double-blind, randomized controlled pilot study

Kade L Paterson, Melissa Nicholls, Kim L Bennell, Dan Bates, Kade L Paterson, Melissa Nicholls, Kim L Bennell, Dan Bates

Abstract

Background: Improvements in knee osteoarthritis (OA) symptoms with platelet-rich plasma (PRP) have been attributed to its ability to modify intra-articular inflammatory processes. Photo-activation of peripheral blood also improves inflammatory mediators associated with OA, however combined photo-activated PRP (PA-PRP) has not been investigated. This pilot study assessed the feasibility, safety and symptomatic and functional change following injections of PA-PRP compared to hyaluronic acid (HA) in people with knee osteoarthritis (OA).

Methods: Thirty seven people with knee OA were enrolled in this double-blind randomized controlled pilot study set in a sports medicine clinic. Participants were randomly allocated to receive three injections of either PA-PRP or HA. The patients and the administering doctor were blinded to group allocation. Outcomes included recruitment and safety data, 100 mm visual analogue pain score (VAS), the Knee Osteoarthritis Outcome Score (KOOS), Knee Quality of Life (KQoL) scale, maximum hopping distance and number of knee bends in 30 s at four and 12 weeks.

Results: Twenty three (62 %) participants met the inclusion criteria, of which 12 (32 %) were randomized to the PA-PRP group and 11 (30 %) to the HA group. Two participants did not complete the intervention and two withdrew following their first assessment. Minor pain and swelling during the injection period was reported by two participants from the PA-PRP group. The PA-PRP group demonstrated significant improvements in the VAS (p < 0.01, ETA = 0.686), KOOS Pain (p < 0.05, ETA = 0.624), KQoL Physical (p < 0.05, ETA = 0.706) and KQoL Emotional subscales (p < 0.05, ETA = 0.715) at four and 12 weeks. The PA-PRP group also significantly improved hoping (p < 0.05, ETA = 0.799) and knee bends (p < 0.01, ETA = 0.756) at four or 12 weeks. The HA group showed improvements on only the KOOS Function subscale at 12 weeks (p < 0.01, ETA = 0.602). After controlling for baseline values, there were no significant between-group differences at either time-point.

Conclusions: This study provides proof-of-concept evidence concerning the feasibility and safety of PA-PRP injections necessary to inform a larger clinical trial in people with knee OA. Our preliminary results also suggest PA-PRP improves self-reported pain, symptoms and lower extremity function, however no between-group differences were found. Photo-activated PRP may provide a safe and effective novel treatment for knee OA.

Trial registration: ACTRN12611000651987.

Figures

Fig. 1
Fig. 1
CONSORT diagram demonstrating flow of participants through the trial

References

    1. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg. 2007;89(4):780–785. doi: 10.2106/JBJS.F.00222.
    1. Harvey WF, Hunter DJ. The role of analgesics and intra-articular injections in disease management. Med Clin North Am. 2009;93(1):201–211. doi: 10.1016/j.mcna.2008.07.010.
    1. Bourne RB, Chesworth BM, Davis AM, Mahomed NN, Charron KD. Patient satisfaction after total knee arthroplasty: who is satisfied and who is not? Clin Orthop Relat Res. 2010;468(1):57–63. doi: 10.1007/s11999-009-1119-9.
    1. Fransen M, McConnell S. Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev. 2008;4(4).
    1. Bjordal JM, Ljunggren AE, Klovning A, Slørdal L. Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials. BMJ. 2004;329(7478):1317. doi: 10.1136/bmj.38273.626655.63.
    1. Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16(2):137–162. doi: 10.1016/j.joca.2007.12.013.
    1. Arrich J, Piribauer F, Mad P, Schmid D, Klaushofer K, Mullner M. Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis. CMAJ. 2005;172(8):1039–1043. doi: 10.1503/cmaj.1041203.
    1. Lo GH, LaValley M, McAlindon T, Felson DT. Intra-articular hyaluronic acid in treatment of knee osteoarthritis: A meta-analysis. JAMA. 2003;290(23):3115–3121. doi: 10.1001/jama.290.23.3115.
    1. Wang C, Lin J, Chang C, Lin Y, Hou S. Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomised controlled trials. J Bone Joint Surg. 2004;86(3):538–545.
    1. Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Cenacchi A, et al. 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. Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol. 2013;9(12):721–730. doi: 10.1038/nrrheum.2013.141.
    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. Sampson S, Gerhardt M, Mandelbaum B. Platelet rich plasma injection grafts for musculoskeletal injuries: A review. Curr Rev Musculoskel Med. 2008;1(3-4):165–174. doi: 10.1007/s12178-008-9032-5.
    1. Sánchez M, Anitua E, Orive G, Mujika I, Andia I. Platelet-rich therapies in the treatment of orthopaedic sport injuries. Sports Med. 2009;39(5):345–354. doi: 10.2165/00007256-200939050-00002.
    1. Filardo G, Kon E, Buda R, Timoncini A, Di Martino A, Cenacchi A, 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.
    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. Sánchez M, Anitua E, Azofra J, Aguirre J, 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. 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.
    1. Filardo G, Kon E, Di Martino A, Di Matteo B, Merli M, Cenacchi 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(1):229. doi: 10.1186/1471-2474-13-229.
    1. Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: A prospective, double-blind, randomized trial. Am J Sports Med. 2013;41(2):356–364. doi: 10.1177/0363546512471299.
    1. World Health Organization. The burden of musculoskeletal conditions at the start of the new millenium. In. Edited by World Health Organization Technical Report Series, vol. 919:i-x; 2003: 1-218.
    1. Sigmundsdottir H, Johnston A, Gudjonsson JE, Valdimarsson H. Narrowband–UVB irradiation decreases the production of pro-inflammatory cytokines by stimulated T cells. Arch Dermatol Res. 2005;297(1):39–42. doi: 10.1007/s00403-005-0565-9.
    1. Zhevago NA, Samoilova KA. Pro-and anti-inflammatory cytokine content in human peripheral blood after its transcutaneous (in vivo) and direct (in vitro) irradiation with polychromatic visible and infrared light. Photomed Laser Ther. 2006;24(2):129–139. doi: 10.1089/pho.2006.24.129.
    1. Freitag J, Barnard A, Rotstein A. Photoactivated platelet-rich plasma therapy for a traumatic knee chondral lesion. BMJ Case Rep. 2012;2012:bcr2012006858.
    1. Freitag JB, Barnard A. To evaluate the effect of combining photo-activation therapy with platelet-rich plasma injections for the novel treatment of osteoarthritis. BMJ case reports. 2013;2013:bcr2012007463. doi: 10.1136/bcr-2012-007463.
    1. Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, et al. Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med. 2015;43(7):1575–1582. doi: 10.1177/0363546515582027.
    1. Trojian TH, Concoff AL, Joy SM, Hatzenbuehler JR, Saulsberry WJ, Coleman CI. AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthritis: importance for individual patient outcomes. Br J Sports Med. 2016;50(2):84–92. doi: 10.1136/bjsports-2015-095683.
    1. Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE. 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.
    1. Hertzog MA. Considerations in determining sample size for pilot studies. Res Nurs Health. 2008;31(2):180–191. doi: 10.1002/nur.20247.
    1. Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat. 2005;4(4):287–291. doi: 10.1002/pst.185.
    1. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee. Arthritis Rheum. 1986;29(8):1039–1049. doi: 10.1002/art.1780290816.
    1. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16(4):494–502. doi: 10.1136/ard.16.4.494.
    1. Chang K-V, Hung C-Y, Aliwarga F, Wang T-G, Han D-S, Chen W-S. Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2014;95(3):562–575. doi: 10.1016/j.apmr.2013.11.006.
    1. Filardo G, Kon E, Pereira Ruiz M, Vaccaro F, Guitaldi R, Di Martino A, 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.
    1. Bellamy N, Carette S, Ford PM, Kean WF, le Riche NG, Lussier A, et al. Osteoarthritis antirheumatic drug trials. II. Tables for calculating sample size for clinical trials. J Rheumatol. 1992;19(3):444–450.
    1. Roos EM, Lohmander LS. The Knee injury and Osteoarthritis Outcome Score (KOOS): From joint injury to osteoarthritis. Health Qual Life Outcomes. 2003;1(1):64. doi: 10.1186/1477-7525-1-64.
    1. Garratt A, Brealey S, Robling M, Atwell C, Russell I, Gillespie W, et al. Development of the Knee Quality of Life (KQoL-26) 26-item questionnaire: data quality, reliability, validity and responsiveness. Health Qual Life Outcomes. 2008;6(1):48. doi: 10.1186/1477-7525-6-48.
    1. Roos EM, Bremander AB, Englund M, Lohmander LS. Change in self-reported outcomes and objective physical function over 7 years in middle-aged subjects with or at high risk of knee osteoarthritis. Ann Rheum Dis. 2008;67(4):505–510. doi: 10.1136/ard.2007.074088.
    1. Bremander AB, Dahl LL, Roos EM. Validity and reliability of functional performance tests in meniscectomized patients with or without knee osteoarthritis. Scand J Med Sci Sports. 2007;17(2):120–127.
    1. Cerza F, Carnì S, Carcangiu A, Di Vavo I, Schiavilla V, Pecora A, et al. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012;40(12):2822–2827. doi: 10.1177/0363546512461902.
    1. Zhang S, Paul J, Nantha-Aree M, Buckley N, Shahzad U, Cheng J, et al. Empirical comparison of four baseline covariate adjustment methods in analysis of continuous outcomes in randomized controlled trials. Clin Epidemiol. 2014;6:227. doi: 10.2147/CLEP.S56554.
    1. Vaquerizo V, Plasencia MÁ, Arribas I, Seijas R, Padilla S, Orive G, et al. Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: A randomized controlled trial. Arthroscopy. 2013;29(10):1635–1643. doi: 10.1016/j.arthro.2013.07.264.
    1. Sánchez M, Fiz N, Azofra J, Usabiaga J, Aduriz Recalde E, Garcia Gutierrez A, et al. 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.
    1. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J-P, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33–42. doi: 10.1038/nrrheum.2010.196.
    1. Zhu Y, Yuan M, Meng HY, Wang AY, Guo QY, Wang Y, et al. Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: A review. Osteoarthritis Cartilage. 2013;21(11):1627–1637. doi: 10.1016/j.joca.2013.07.017.
    1. Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med. 2014;42(1):35-41.
    1. Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole BJ. Effect of leukocyte concentration on the efficacy of platelet-rich plasma in the treatment of knee osteoarthritis. Am J Sports Med. 2015

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