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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.


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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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

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.

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Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
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