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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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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).

References
1.
Hunter  DJ , Bierma-Zeinstra  S .  Osteoarthritis.   Lancet. 2019;393(10182):1745-1759. doi:10.1016/S0140-6736(19)30417-9PubMedGoogle ScholarCrossref
2.
Murray  C , Marshall  M , Rathod  T , Bowen  CJ , Menz  HB , Roddy  E .  Population prevalence and distribution of ankle pain and symptomatic radiographic ankle osteoarthritis in community dwelling older adults: a systematic review and cross-sectional study.   PLoS One. 2018;13(4):e0193662. doi:10.1371/journal.pone.0193662PubMedGoogle Scholar
3.
Glazebrook  M , Daniels  T , Younger  A ,  et al.  Comparison of health-related quality of life between patients with end-stage ankle and hip arthrosis.   J Bone Joint Surg Am. 2008;90(3):499-505. doi:10.2106/JBJS.F.01299PubMedGoogle ScholarCrossref
4.
Saltzman  CL , Zimmerman  MB , O’Rourke  M , Brown  TD , Buckwalter  JA , Johnston  R .  Impact of comorbidities on the measurement of health in patients with ankle osteoarthritis.   J Bone Joint Surg Am. 2006;88(11):2366-2372. doi:10.2106/JBJS.F.00295PubMedGoogle ScholarCrossref
5.
Vannabouathong  C , Del Fabbro  G , Sales  B ,  et al.  Intra-articular injections in the treatment of symptoms from ankle arthritis: a systematic review.   Foot Ankle Int. 2018;39(10):1141-1150. doi:10.1177/1071100718779375PubMedGoogle ScholarCrossref
6.
Witteveen  AGH , Hofstad  CJ , Kerkhoffs  GMMJ .  Hyaluronic acid and other conservative treatment options for osteoarthritis of the ankle.   Cochrane Database Syst Rev. 2015;(10):CD010643. doi:10.1002/14651858.CD010643.pub2PubMedGoogle Scholar
7.
Dong  Y , Zhang  B , Yang  Q , Zhu  J , Sun  X .  The effects of platelet-rich plasma injection in knee and hip osteoarthritis: a meta-analysis of randomized controlled trials.   Clin Rheumatol. 2021;40(1):263-277. doi:10.1007/s10067-020-05185-2PubMedGoogle ScholarCrossref
8.
Global platelet rich plasma (PRP) market 2019 by manufacturers, regions, type and application, forecast to 2024. Published February 22, 2019. Accessed September 27, 2021. https://www.industryresearch.biz/global-platelet-rich-plasma-prp-market-13877695
9.
Platelet rich plasma market size, share & trends analysis report by type, by application (orthopedics, sports medicine, cosmetic surgery), by end-use (hospitals, clinics), by region, and segment forecasts, 2021-2028. Grand View Research. Published February 2021. Accessed September 30, 2021. https://www.grandviewresearch.com/industry-analysis/platelet-rich-plasma-prp-market
10.
Filardo  G , Kon  E , Roffi  A , Di Matteo  B , Merli  ML , Marcacci  M .  Platelet-rich plasma: why intra-articular? a systematic review of preclinical studies and clinical evidence on PRP for joint degeneration.   Knee Surg Sports Traumatol Arthrosc. 2015;23(9):2459-2474. doi:10.1007/s00167-013-2743-1PubMedGoogle ScholarCrossref
11.
Zhu  Y , Yuan  M , Meng  HY ,  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.2013.07.017PubMedGoogle ScholarCrossref
12.
Sun  SF , Hsu  CW , Lin  GC ,  et al.  Efficacy and safety of a single intra-articular injection of platelet-rich plasma on pain and physical function in patients with ankle osteoarthritis: a prospective study.   J Foot Ankle Surg. 2021;60(4):676-682. doi:10.1053/j.jfas.2020.12.003PubMedGoogle ScholarCrossref
13.
Paget  L , Bierma-Zeinstra  S , Goedegebuure  S ,  et al.  Platelet-rich plasma injection management for ankle osteoarthritis study (PRIMA): protocol of a Dutch multicentre, stratified, block-randomised, double-blind, placebo-controlled trial.   BMJ Open. 2019;9(10):e030961. doi:10.1136/bmjopen-2019-030961PubMedGoogle Scholar
14.
McDermott  MM , Newman  AB .  Preserving clinical trial integrity during the coronavirus pandemic.   JAMA. 2020;323(21):2135-2136. doi:10.1001/jama.2020.4689PubMedGoogle ScholarCrossref
15.
van Dijk  CN , Verhagen  RA , Tol  JL .  Arthroscopy for problems after ankle fracture.   J Bone Joint Surg Br. 1997;79(2):280-284. doi:10.1302/0301-620X.79B2.0790280PubMedGoogle ScholarCrossref
16.
Smith  PA .  Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee osteoarthritis: an FDA-sanctioned, randomized, double-blind, placebo-controlled clinical trial.   Am J Sports Med. 2016;44(4):884-891. doi:10.1177/0363546515624678PubMedGoogle ScholarCrossref
17.
Cole  BJ , Karas  V , Hussey  K , Pilz  K , Fortier  LA .  Hyaluronic acid versus platelet-rich plasma: a prospective, double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis.   Am J Sports Med. 2017;45(2):339-346. doi:10.1177/0363546516665809PubMedGoogle ScholarCrossref
18.
Reurink  G , Goudswaard  GJ , Moen  MH ,  et al; Dutch Hamstring Injection Therapy (HIT) Study Investigators.  Platelet-rich plasma injections in acute muscle injury.   N Engl J Med. 2014;370(26):2546-2547. doi:10.1056/NEJMc1402340PubMedGoogle ScholarCrossref
19.
de Boer  AS , Tjioe  RJC , Van der Sijde  F ,  et al; AOFAS Study Group.  The American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale: translation and validation of the Dutch language version for ankle fractures.   BMJ Open. 2017;7(8):e017040. doi:10.1136/bmjopen-2017-017040PubMedGoogle Scholar
20.
Madeley  NJ , Wing  KJ , Topliss  C , Penner  MJ , Glazebrook  MA , Younger  ASE .  Responsiveness and validity of the SF-36, ankle osteoarthritis scale, AOFAS ankle hindfoot score, and foot function index in end stage ankle arthritis.   Foot Ankle Int. 2012;33(1):57-63. doi:10.3113/FAI.2012.0057PubMedGoogle ScholarCrossref
21.
Sierevelt  IN , Beimers  L , van Bergen  CJA , Haverkamp  D , Terwee  CB , Kerkhoffs  GMMJ .  Validation of the Dutch language version of the Foot and Ankle Outcome Score.   Knee Surg Sports Traumatol Arthrosc. 2015;23(8):2413-2419. doi:10.1007/s00167-014-3017-2PubMedGoogle ScholarCrossref
22.
Glazebrook  M , Burgesson  BN , Younger  AS , Daniels  TR .  Clinical outcome results of total ankle replacement and ankle arthrodesis: a pilot randomised controlled trial.   Foot Ankle Surg. 2021;27(3):326-331. doi:10.1016/j.fas.2020.10.005PubMedGoogle ScholarCrossref
23.
Suo  H , Fu  L , Liang  H , Wang  Z , Men  J , Feng  W .  End-stage ankle arthritis treated by ankle arthrodesis with screw fixation through the transfibular approach: a retrospective analysis.   Orthop Surg. 2020;12(4):1108-1119. doi:10.1111/os.12707PubMedGoogle ScholarCrossref
24.
Halasi  T , Kynsburg  A , Tállay  A , Berkes  I .  Development of a new activity score for the evaluation of ankle instability.   Am J Sports Med. 2004;32(4):899-908. doi:10.1177/0363546503262181PubMedGoogle ScholarCrossref
25.
Turner-Stokes  L .  Goal attainment scaling (GAS) in rehabilitation: a practical guide.   Clin Rehabil. 2009;23(4):362-370. doi:10.1177/0269215508101742PubMedGoogle ScholarCrossref
26.
Lamers  LM , Stalmeier  PFM , McDonnell  J , Krabbe  PFM , van Busschbach  JJ .  Measuring the quality of life in economic evaluations: the Dutch EQ-5D tariff.   Ned Tijdschr Geneeskd. 2005;149(28):1574-1578.PubMedGoogle Scholar
27.
Pham  T , van der Heijde  D , Altman  RD ,  et al.  OMERACT-OARSI initiative: Osteoarthritis research society international set of responder criteria for osteoarthritis clinical trials revisited.   Osteoarthritis Cartilage. 2004;12(5):389-399. doi:10.1016/j.joca.2004.02.001PubMedGoogle ScholarCrossref
28.
de Vos  RJ , Weir  A , van Schie  HTM ,  et al.  Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial.   JAMA. 2010;303(2):144-149. doi:10.1001/jama.2009.1986PubMedGoogle ScholarCrossref
29.
Rozendaal  RM , Koes  BW , van Osch  GJVM ,  et al.  Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial.   Ann Intern Med. 2008;148(4):268-277. doi:10.7326/0003-4819-148-4-200802190-00005PubMedGoogle ScholarCrossref
30.
Järvinen  TLN , Sihvonen  R , Bhandari  M ,  et al.  Blinded interpretation of study results can feasibly and effectively diminish interpretation bias.   J Clin Epidemiol. 2014;67(7):769-772. doi:10.1016/j.jclinepi.2013.11.011PubMedGoogle ScholarCrossref
31.
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
32.
Wu  YT , Hsu  KC , Li  TY , Chang  CK , Chen  LC .  Effects of platelet-rich plasma on pain and muscle strength in patients with knee osteoarthritis.   Am J Phys Med Rehabil. 2018;97(4):248-254. doi:10.1097/PHM.0000000000000874PubMedGoogle ScholarCrossref
33.
Görmeli  G , Görmeli  CA , Ataoglu  B , Çolak  C , Aslantürk  O , Ertem  K .  Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial.   Knee Surg Sports Traumatol Arthrosc. 2017;25(3):958-965. doi:10.1007/s00167-015-3705-6PubMedGoogle ScholarCrossref
34.
Saltzman  BM , Leroux  T , Meyer  MA ,  et al.  The therapeutic effect of intra-articular normal saline injections for knee osteoarthritis: a meta-analysis of evidence level 1 studies.   Am J Sports Med. 2017;45(11):2647-2653. doi:10.1177/0363546516680607PubMedGoogle ScholarCrossref
35.
Leopoldino  AO , Machado  GC , Ferreira  PH ,  et al.  Paracetamol versus placebo for knee and hip osteoarthritis.   Cochrane Database Syst Rev. 2019;2(2):CD013273. doi:10.1002/14651858.CD013273PubMedGoogle Scholar
36.
Moseley  JB , O’Malley  K , Petersen  NJ ,  et al.  A controlled trial of arthroscopic surgery for osteoarthritis of the knee.   N Engl J Med. 2002;347(2):81-88. doi:10.1056/NEJMoa013259PubMedGoogle ScholarCrossref
37.
Bradley  JD , Heilman  DK , Katz  BP , Gsell  P , Wallick  JE , Brandt  KD .  Tidal irrigation as treatment for knee osteoarthritis: a sham-controlled, randomized, double-blinded evaluation.   Arthritis Rheum. 2002;46(1):100-108. doi:10.1002/1529-0131(200201)46:1<100::AID-ART10037>3.0.CO;2-VPubMedGoogle ScholarCrossref
38.
Castillo  TN , Pouliot  MA , Kim  HJ , Dragoo  JL .  Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems.   Am J Sports Med. 2011;39(2):266-271. doi:10.1177/0363546510387517PubMedGoogle ScholarCrossref
39.
Angthong  C , Khadsongkram  A , Angthong  W .  Outcomes and quality of life after platelet-rich plasma therapy in patients with recalcitrant hindfoot and ankle diseases: a preliminary report of 12 patients.   J Foot Ankle Surg. 2013;52(4):475-480. doi:10.1053/j.jfas.2013.04.005PubMedGoogle ScholarCrossref
40.
Mariani  E , Pulsatelli  L .  Platelet concentrates in musculoskeletal medicine.   Int J Mol Sci. 2020;21(4):1328. doi:10.3390/ijms21041328PubMedGoogle ScholarCrossref
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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.

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