Effect of Intra-articular Platelet-Rich Plasma vs Placebo on Pain and Cartilage Volume in Knee Osteoarthritis | Geriatrics | JN Learning | AMA Ed Hub [Skip to Content]
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Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee OsteoarthritisThe RESTORE Randomized Clinical Trial

Educational Objective
To learn the effect of platelet-rich plasma on symptoms and pathophysiology of knee osteoarthritis.
1 Credit CME
Key Points

Question  Does intra-articular injection of platelet-rich plasma (PRP), compared with placebo saline injection, improve symptoms and joint structure in patients with knee osteoarthritis?

Findings  In this randomized clinical trial that included 288 adults aged 50 years or older with mild to moderate radiographic knee osteoarthritis, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of −2.1 vs −1.8 on an 11-point scale (range, 0-10) and a mean change in medial tibial cartilage volume of −1.4% vs −1.2% at 12 months. Neither comparison was statistically significant.

Meaning  Among adults with mild to moderate knee osteoarthritis, treatment with PRP vs saline injection did not significantly improve knee pain or slow disease progression.

Abstract

Importance  Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.

Objective  To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.

Design, Setting, and Participants  This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020.

Interventions  Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants).

Main Outcomes and Measures  The 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up.

Results  Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of −2.1 vs −1.8 points, respectively (difference, −0.4 [95% CI, −0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was −1.4% vs −1.2%, respectively (difference, −0.2% [95% CI, −1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences.

Conclusions and Relevance  Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA.

Trial Registration  Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347

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Article Information

Corresponding Author: Kim L. Bennell, PhD, Centre for Health, Exercise and Sports Medicine, Department of Physiotherapy, The University of Melbourne, 161 Barry St, Carlton, VIC 3010, Australia (k.bennell@unimelb.edu.au).

Accepted for Publication: October 12, 2021.

Author Contributions: Drs Bennell and Kasza had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Bennell and Paterson are co–first authors and contributed equally to the article.

Concept and design: Bennell, Paterson, Kasza, Y. Wang, Cicuttini, Buchbinder, Harris, Connell, Linklater, Hunter.

Acquisition, analysis, or interpretation of data: Bennell, Metcalf, Duong, Eyles, Kasza, Y. Wang, Cicuttini, Buchbinder, Forbes, Yu, Connell, Linklater, B. Wang, Oo, Hunter.

Drafting of the manuscript: Bennell, Paterson, Metcalf, Kasza, Linklater.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Metcalf, Kasza, Forbes.

Obtained funding: Bennell, Y. Wang, Buchbinder, Hunter.

Administrative, technical, or material support: Paterson, Metcalf, Duong, Eyles, Cicuttini, Harris, Yu, Linklater, B. Wang.

Supervision: Bennell, Paterson, Eyles, Y. Wang, Cicuttini, Connell, Linklater, Hunter.

Conflict of Interest Disclosures: Dr Bennell reported receiving personal fees from Wolters Kluwer for production of UpToDate knee OA clinical guidelines. Dr Paterson reported receiving grants from the Australian National Health and Medical Research Council (NHMRC) outside the submitted work. Dr Buchbinder report receiving funding from the NHMRC outside the submitted work. Dr Yu reported receiving royalties from Wolters Kluwer for contributions to UpToDate. Mr Connell reported providing PRP injections in clinical practice (Imaging @ Olympic Park). Dr Linklater reported providing PRP injections in clinical practice (Castlereagh Imaging). Dr Hunter reported receiving personal fees for scientific advisory board membership from Biobone, Novartis, Tissuegene, Pfizer, and Lilly. No other disclosures were reported.

Funding/Support: The study was funded by NHMRC project grant 1106274. Regen Lab SA provided the commercial kits free of charge.

Role of the Funder/Sponsor: The NHMRC, the University of Melbourne, and Regen Lab SA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 4.

Additional Contributions: We thank Paris Arlegui (Imaging @ Olympic Park), for administrative assistance; Jade McTernan, BSc, Naomi Haverty, BSN, and Tom Entwisle, MBBS (all from Imaging @ Olympic Park), and Annie Phillips, DipAppSci, Jennie Noakes, BMed, and Danielle Pryke, GDip (all from Castlereagh Imaging), for assisting with administration of PRP injections; and Sarah Robbins, BPhty (University of Sydney), for assisting with project management. Their roles were supported through the NHMRC research grant.

References
1.
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators.  Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.   Lancet. 2018;392(10159):1789-1858. doi:10.1016/S0140-6736(18)32279-7PubMedGoogle ScholarCrossref
2.
Bannuru  RR , Osani  MC , Vaysbrot  EE ,  et al.  OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis.   Osteoarthritis Cartilage. 2019;27(11):1578-1589. doi:10.1016/j.joca.2019.06.011PubMedGoogle ScholarCrossref
3.
Kolasinski  SL , Neogi  T , Hochberg  MC ,  et al.  2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee.   Arthritis Rheumatol. 2020;72(2):220-233. doi:10.1002/art.41142PubMedGoogle ScholarCrossref
4.
Fice  MP , Miller  JC , Christian  R ,  et al.  The role of platelet-rich plasma in cartilage pathology: an updated systematic review of the basic science evidence.   Arthroscopy. 2019;35(3):961-976.e3. doi:10.1016/j.arthro.2018.10.125PubMedGoogle ScholarCrossref
5.
Werner  BC , Cancienne  JM , Browning  R , Verma  NN , Cole  BJ .  An analysis of current treatment trends in platelet-rich plasma therapy in the Medicare database.   Orthop J Sports Med. 2020;8(2):2325967119900811. doi:10.1177/2325967119900811PubMedGoogle Scholar
6.
Hohmann  E , Tetsworth  K , Glatt  V .  Is platelet-rich plasma effective for the treatment of knee osteoarthritis? a systematic review and meta-analysis of level 1 and 2 randomized controlled trials.   Eur J Orthop Surg Traumatol. 2020;30(6):955-967. doi:10.1007/s00590-020-02623-4PubMedGoogle ScholarCrossref
7.
Shen  L , Yuan  T , Chen  S , Xie  X , Zhang  C .  The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials.   J Orthop Surg Res. 2017;12(1):16. doi:10.1186/s13018-017-0521-3PubMedGoogle ScholarCrossref
8.
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:10.1177/0363546512471299PubMedGoogle ScholarCrossref
9.
Buendía-López  D , Medina-Quirós  M , Fernández-Villacañas Marín  MA .  Clinical and radiographic comparison of a single LP-PRP injection, a single hyaluronic acid injection and daily NSAID administration with a 52-week follow-up: a randomized controlled trial.   J Orthop Traumatol. 2018;19(1):3. doi:10.1186/s10195-018-0501-3PubMedGoogle ScholarCrossref
10.
Elik  H , Doğu  B , Yılmaz  F , Begoğlu  FA , Kuran  B .  The efficiency of platelet-rich plasma treatment in patients with knee osteoarthritis.   J Back Musculoskelet Rehabil. 2020;33(1):127-138. doi:10.3233/BMR-181374PubMedGoogle ScholarCrossref
11.
Ahmad  HS , Farrag  SE , Okasha  AE ,  et al.  Clinical outcomes are associated with changes in ultrasonographic structural appearance after platelet-rich plasma treatment for knee osteoarthritis.   Int J Rheum Dis. 2018;21(5):960-966. doi:10.1111/1756-185X.13315PubMedGoogle ScholarCrossref
12.
Paterson  KL , Hunter  DJ , Metcalf  BR ,  et al.  Efficacy of intra-articular injections of platelet-rich plasma as a symptom- and disease-modifying treatment for knee osteoarthritis—the RESTORE trial protocol.   BMC Musculoskelet Disord. 2018;19(1):272. doi:10.1186/s12891-018-2205-5PubMedGoogle ScholarCrossref
13.
Murray  IR , Geeslin  AG , Goudie  EB , Petrigliano  FA , LaPrade  RF .  Minimum information for studies evaluating biologics in orthopaedics (MIBO): platelet-rich plasma and mesenchymal stem cells.   J Bone Joint Surg Am. 2017;99(10):809-819. doi:10.2106/JBJS.16.00793PubMedGoogle ScholarCrossref
14.
Kellgren  JH , Lawrence  JS .  Radiological assessment of osteo-arthrosis.   Ann Rheum Dis. 1957;16(4):494-502. doi:10.1136/ard.16.4.494PubMedGoogle ScholarCrossref
15.
Altman  RD , Gold  GE .  Atlas of individual radiographic features in osteoarthritis, revised.   Osteoarthritis Cartilage. 2007;15(suppl A):A1-A56. doi:10.1016/j.joca.2006.11.009PubMedGoogle ScholarCrossref
16.
Bennell  KL , Hunter  DJ , Paterson  KL .  Platelet-rich plasma for the management of hip and knee osteoarthritis.   Curr Rheumatol Rep. 2017;19(5):24. doi:10.1007/s11926-017-0652-xPubMedGoogle ScholarCrossref
17.
RegenBCT Tube Performance. Version 3. Regen Lab; February 25, 2015.
18.
Kon  E , Di Matteo  B , Delgado  D ,  et al.  Platelet-rich plasma for the treatment of knee osteoarthritis: an expert opinion and proposal for a novel classification and coding system.   Expert Opin Biol Ther. 2020;20(12):1447-1460. doi:10.1080/14712598.2020.1798925PubMedGoogle ScholarCrossref
19.
Bellamy  N , Carette  S , Ford  PM ,  et al.  Osteoarthritis antirheumatic drug trials, II: tables for calculating sample size for clinical trials.   J Rheumatol. 1992;19(3):444-450.PubMedGoogle Scholar
20.
Hawker  GA , Davis  AM , French  MR ,  et al.  Development and preliminary psychometric testing of a new OA pain measure—an OARSI/OMERACT initiative.   Osteoarthritis Cartilage. 2008;16(4):409-414. doi:10.1016/j.joca.2007.12.015PubMedGoogle ScholarCrossref
21.
Roos  EM , Roos  HP , Lohmander  LS , Ekdahl  C , Beynnon  BD .  Knee Injury and Osteoarthritis Outcome Score (KOOS)—development of a self-administered outcome measure.   J Orthop Sports Phys Ther. 1998;28(2):88-96. doi:10.2519/jospt.1998.28.2.88PubMedGoogle ScholarCrossref
22.
Richardson  J , Iezzi  A , Khan  MA , Maxwell  A .  Validity and reliability of the Assessment of Quality of Life (AQoL)–8D multi-attribute utility instrument.   Patient. 2014;7(1):85-96. doi:10.1007/s40271-013-0036-xPubMedGoogle ScholarCrossref
23.
ten Klooster  PM , Drossaers-Bakker  KW , Taal  E , van de Laar  MA .  Patient-Perceived Satisfactory Improvement (PPSI): interpreting meaningful change in pain from the patient’s perspective.   Pain. 2006;121(1-2):151-157. doi:10.1016/j.pain.2005.12.021PubMedGoogle Scholar
24.
Hunter  DJ , Guermazi  A , Lo  GH ,  et al.  Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score).   Osteoarthritis Cartilage. 2011;19(8):990-1002. doi:10.1016/j.joca.2011.05.004PubMedGoogle ScholarCrossref
25.
Cicuttini  FM , Jones  G , Forbes  A , Wluka  AE .  Rate of cartilage loss at two years predicts subsequent total knee arthroplasty: a prospective study.   Ann Rheum Dis. 2004;63(9):1124-1127. doi:10.1136/ard.2004.021253PubMedGoogle ScholarCrossref
26.
Bennell  KL , Bowles  KA , Payne  C ,  et al.  Lateral wedge insoles for medial knee osteoarthritis: 12 month randomised controlled trial.   BMJ. 2011;342(7808):d2912. doi:10.1136/bmj.d2912PubMedGoogle Scholar
27.
Carpenter  JG , Kenward  MG .  Multiple Imputation and Its Application. John Wiley & Sons Ltd; 2013. doi:10.1002/9781119942283
28.
James  KE , Bloch  DA , Lee  KK , Kraemer  HC , Fuller  RK .  An index for assessing blindness in a multi-centre clinical trial: disulfiram for alcohol cessation—a VA cooperative study.   Stat Med. 1996;15(13):1421-1434. doi:10.1002/(SICI)1097-0258(19960715)15:13<1421::AID-SIM266>3.0.CO;2-HPubMedGoogle ScholarCrossref
29.
Royston  P , Sauerbrei  W .  A new approach to modelling interactions between treatment and continuous covariates in clinical trials by using fractional polynomials.   Stat Med. 2004;23(16):2509-2525. doi:10.1002/sim.1815PubMedGoogle ScholarCrossref
30.
Hong  M , Cheng  C , Sun  X ,  et al.  Efficacy and safety of intra-articular platelet-rich plasma in osteoarthritis knee: a systematic review and meta-analysis.   Biomed Res Int. 2021;2021:2191926. doi:10.1155/2021/2191926PubMedGoogle Scholar
31.
McAlindon  TE , Driban  JB , Henrotin  Y ,  et al.  OARSI clinical trials recommendations: design, conduct, and reporting of clinical trials for knee osteoarthritis.   Osteoarthritis Cartilage. 2015;23(5):747-760. doi:10.1016/j.joca.2015.03.005PubMedGoogle ScholarCrossref
32.
Hunter  DJ , Altman  RD , Cicuttini  F ,  et al.  OARSI clinical trials recommendations: knee imaging in clinical trials in osteoarthritis.   Osteoarthritis Cartilage. 2015;23(5):698-715. doi:10.1016/j.joca.2015.03.012PubMedGoogle ScholarCrossref
33.
Belk  JW , Kraeutler  MJ , Houck  DA , Goodrich  JA , Dragoo  JL , McCarty  EC .  Platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.   Am J Sports Med. 2021;49(1):249-260. doi:10.1177/0363546520909397PubMedGoogle ScholarCrossref
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