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Effect of Platelet-Rich Plasma Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle OsteoarthritisA Randomized Clinical Trial

Educational Objective
To learn whether injections of platelet-rich plasma improve symptoms and function in patients with ankle osteoarthritis.
1 Credit CME
Key Points

Question  Do intra-articular platelet-rich plasma injections improve ankle symptoms and function in patients with ankle osteoarthritis?

Findings  In this randomized clinical trial that included 100 patients, treatment with 2 intra-articular platelet-rich plasma injections vs placebo injections with saline resulted in a mean change in the American Orthopaedic Foot and Ankle Society score (range, 0-100; higher scores indicate less pain and better function) of 10 vs 11 points over 26 weeks; the between-group difference was not statistically significant.

Meaning  These findings do not support the use of platelet-rich plasma injections for patients with ankle osteoarthritis.

Abstract

Importance  Approximately 3.4% of adults have ankle (tibiotalar) osteoarthritis and, among younger patients, ankle osteoarthritis is more common than knee and hip osteoarthritis. Few effective nonsurgical interventions exist, but platelet-rich plasma (PRP) injections are widely used, with some evidence of efficacy in knee osteoarthritis.

Objective  To determine the effect of PRP injections on symptoms and function in patients with ankle osteoarthritis.

Design, Setting, and Participants  A multicenter, block-randomized, double-blinded, placebo-controlled clinical trial performed at 6 sites in the Netherlands that included 100 patients with pain greater than 40 on a visual analog scale (range, 0-100) and tibiotalar joint space narrowing. Enrollment began on August 24, 2018, and follow-up was completed on December 3, 2020.

Interventions  Patients were randomly assigned (1:1) to receive 2 ultrasonography-guided intra-articular injections of either PRP (n = 48) or placebo (saline; n = 52).

Main Outcomes and Measures  The primary outcome was the validated American Orthopaedic Foot and Ankle Society score (range, 0-100; higher scores indicate less pain and better function; minimal clinically important difference, 12 points) over 26 weeks.

Results  Among 100 randomized patients (mean age, 56 years; 45 [45%] women), no patients were lost to follow-up for the primary outcome. Compared with baseline values, the mean American Orthopaedic Foot and Ankle Society score improved by 10 points in the PRP group (from 63 to 73 points [95% CI, 6-14]; P < .001) and 11 points in the placebo group (from 64 to 75 points [95% CI, 7-15]; P < .001). The adjusted between-group difference over 26 weeks was −1 ([95% CI, –6 to 3]; P = .56). One serious adverse event was reported in the placebo group, which was unrelated to the intervention; there were 13 other adverse events in the PRP group and 8 in the placebo group.

Conclusions and Relevance  Among patients with ankle osteoarthritis, intra-articular PRP injections, compared with placebo injections, did not significantly improve ankle symptoms and function over 26 weeks. The results of this study do not support the use of PRP injections for ankle osteoarthritis.

Trial Registration  Netherlands Trial Register: NTR7261

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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: Liam D. A. Paget, MD, Amsterdam UMC, University of Amsterdam, Department of Orthopedic Surgery, Amsterdam Movement Sciences, PO Box 22660, 1100 DD Amsterdam, the Netherlands (L.d.paget@amsterdamumc.nl).

Accepted for Publication: September 10, 2021.

Author Contributions: Dr Paget had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Paget, Reurink, Tol.

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

Statistical analysis: Paget, Reurink, de Vos, Weir, Bierma-Zeinstra, Tol.

Obtained funding: de Vos, Moen, Kerkhoffs, Tol.

Administrative, technical, or material support: Paget, Reurink, Weir, Moen, Stufkens, Kerkhoffs, Tol.

Supervision: Reurink, Tol.

Conflict of Interest Disclosures: Dr Paget reported receiving an institutional grant from the Dutch Arthritis Society and institutional nonfinancial support from Arthrex (Hettich centrifuge on loan) during the conduct of the study. Dr Reurink reported receiving an institutional grant from the Dutch Arthritis Society and institutional nonfinancial support from Arthrex (Hettich centrifuge on loan) during the conduct of the study. Dr de Vos reported receiving institutional nonfinancial support from Arthrex (Hettich centrifugation system on loan) during the conduct of the study. Dr Weir reported receiving institutional nonfinancial support from Arthrex (Hettich centrifugation system) on loan during the conduct of the study. Dr Moen reported receiving institutional nonfinancial support from Arthrex (Hettich centrifuge on loan) during the conduct of the study. Dr Bierma-Zeinstra reported receiving or having independent research grants pending from The Netherlands Organisation for Health Research and Development, CZ, European Union, Foreum, the Dutch Arthritis Society, personal fees from Osteoarthritis Research Society International as an associate editor of Osteoarthritis and Cartilage, and consultancy fees from Pfizer outside the submitted work. Dr Stufkens reported receiving an institutional grant from the Dutch Arthritis Society and institutional nonfinancial support from Arthrex (Hettich centrifuge on loan) during the conduct of the study. Dr Kerkhoffs reported receiving an institutional grant from the Dutch Arthritis Society and nonfinancial support from Arthrex (Hettich centrifuge on loan) during the conduct of the study and grants from Arthrex for research-related payments and personal fees as an associate editor for the Knee Surgery, Sports Traumatology, Arthroscopy outside the submitted work. Dr Tol reported grants from the Dutch Arthritis Society (a Dutch nonprofit patient organization) and institutional nonfinancial support from Arthrex (Hettich centrifuge on loan) during the conduct of the study.

Funding/Support: This study was supported by a grant from the Dutch Arthritis Society.

Role of the Funder/Sponsor: The funder of the study (The Dutch Arthritis Society [nonprofit patient organization]) had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The platelet-rich plasma centrifugation system was on loan from Arthrex (Arthrex Medizinische Instrumente GmbH), as is customary under usual care.

Group Information: PRIMA Study Group members are shown in Supplement 3.

Data Sharing Statement: See Supplement 4.

Additional Contributions: In addition to the named authors, the PRIMA study group included Simon Goedegebuure, MD (primary investigator [PI]; The Sport Physician Group, Department of Sports Medicine, OLVG); Rover Krips, PhD (PI; Department of Orthopaedic Surgery, Flevoziekenhuis); Mario Maas, PhD (Amsterdam UMC, University of Amsterdam, Department of Radiology and Nuclear Medicine, Division of Musculoskeletal Radiology); Duncan E. Meuffels, PhD (Department of Orthopaedic Surgery and Sports Medicine, Erasmus University Medical Center); and Peter A. Nolte, PhD (PI; Department of Orthopaedic Surgery, Spaarne Gasthuis). We thank the Dutch Arthritis Society, a nonprofit patient organization, for funding this study. None of the following contributors received compensation for their role in the study. We appreciate the time, effort, and precision that the independent statistical expert Jos Runhaar, PhD (Erasmus MC University Medical Center, Rotterdam, the Netherlands), and independent investigator Teppo Järvinen, PhD (University of Helsinki, Helsinki University Central Hospital, Finland), dedicated to this study. We also thank the research assistants and administrative staff at all locations for their diligence and flexibility: J. Nienke Altink (Amsterdam UMC, the Netherlands), Myrthe T. Beekhuis-Heerema, MD (OLVG, Amsterdam, the Netherlands); Rosemary van den Berg (OLVG, Amsterdam, the Netherlands); Robin P. Blom, MD (Flevoziekenhuis, Almere, the Netherlands); Tristan M. F. Buck (Amsterdam UMC, the Netherlands); Jari Dahmen, MD (Amsterdam UMC, the Netherlands); Quinten Dusoswa, MD (Flevoziekenhuis, Almere, the Netherlands); Kaj S. Emanuel, PhD (Amsterdam UMC, the Netherlands); Eline M. van Es, MSc (Erasmus MC University Medical Center, Rotterdam, the Netherlands); Mienie Hermans (Flevoziekenhuis, Almere, the Netherlands); Alexander Hoorntje, MD (Flevoziekenhuis, Almere, the Netherlands); Ozgur Kilic, MD (Amsterdam UMC, the Netherlands); Anne D. van der Made, MD (Amsterdam UMC, the Netherlands); Marjo van der Poel (Spaarne Gasthuis, Hoofddorp, the Netherlands); Christine M. E. Rustenburger, PhD (Amsterdam UMC, the Netherlands); Marjolein Schager, M.Th. (Spaarne Gasthuis, Hoofddorp, the Netherlands); T. Stornebrink, MD (Amsterdam UMC, the Netherlands); Joep J. M. Suskens, MSc (Amsterdam UMC, the Netherlands); Lukas P. E. Verweij (Amsterdam UMC, the Netherlands); Gwendolyn Vuurberg, PhD (Amsterdam UMC, the Netherlands); Tom G. H.Wiggers, MD (OLVG, Amsterdam, the Netherlands); Annika Willems, MSc (Erasmus MC University Medical Center, Rotterdam, the Netherlands); and Tugba Ulucay (Amsterdam UMC, the Netherlands).

AMA CME Accreditation Information

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;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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