Systematic Review
The Efficacy of Platelet-Rich Plasma in the Treatment of Symptomatic Knee Osteoarthritis: A Systematic Review With Quantitative Synthesis

https://doi.org/10.1016/j.arthro.2013.09.006Get rights and content

Purpose

The purpose of this systematic review was to synthesize the available Level I and Level II literature on platelet-rich plasma (PRP) as a therapeutic intervention in the management of symptomatic knee osteoarthritis (OA).

Methods

A systematic review of Medline, Embase, Cochrane Central Register of Controlled Trials, PubMed, and www.clinicaltrials.gov was performed to identify all randomized controlled trials and prospective cohort studies that evaluated the clinical efficacy of PRP versus a control injection for knee OA. A random-effects model was used to evaluate the therapeutic effect of PRP at 24 weeks by use of validated outcome measures (Western Ontario and McMaster Universities Arthritis Index, visual analog scale for pain, International Knee Documentation Committee Subjective Knee Evaluation Form, and overall patient satisfaction).

Results

Six Level I and II studies satisfied our inclusion criteria (4 randomized controlled trials and 2 prospective nonrandomized studies). A total of 577 patients were included, with 264 patients (45.8%) in the treatment group (PRP) and 313 patients (54.2%) in the control group (hyaluronic acid [HA] or normal saline solution [NS]). The mean age of patients receiving PRP was 56.1 years (51.5% male patients) compared with 57.1 years (49.5% male patients) for the group receiving HA or NS. Pooled results using the Western Ontario and McMaster Universities Arthritis Index scale (4 studies) showed that PRP was significantly better than HA or NS injections (mean difference, −18.0 [95% confidence interval, −28.8 to −8.3]; P < .001). Similarly, the International Knee Documentation Committee scores (3 studies) favored PRP as a treatment modality (mean difference, 7.9 [95% confidence interval, 3.7 to 12.1]; P < .001). There was no difference in the pooled results for visual analog scale score or overall patient satisfaction. Adverse events occurred more frequently in patients treated with PRP than in those treated with HA/placebo (8.4% v 3.8%, P = .002).

Conclusions

As compared with HA or NS injection, multiple sequential intra-articular PRP injections may have beneficial effects in the treatment of adult patients with mild to moderate knee OA at approximately 6 months. There appears to be an increased incidence of nonspecific adverse events among patients treated with PRP.

Level of evidence

Level II, systematic review of Level I and II studies.

Section snippets

Inclusion and Exclusion Criteria

All published randomized controlled trials (RCTs) or prospective cohort studies (PCSs) that evaluated the clinical efficacy of intra-articular PRP (or similarly defined preparations—autologous platelet concentrate, autologous conditioned plasma, or platelet-rich growth factors) against either HA or placebo (defined as normal saline solution [NS]) in the treatment of knee OA in humans were eligible for inclusion. It was decided a priori that only RCTs (deemed Level I studies) or prospective

Baseline Demographics

The results of our literature search are depicted in the study selection log (Fig 1). After the search, review, and assessment, 4 Level I randomized trials17, 36, 41, 42 and 2 Level II PCSs with comparative control groups22, 43 were included. All studies were published in peer-reviewed journals. Of the 6 studies, 5 were written in English17, 22, 36, 41, 43 and one required translation (Chinese to English) by a bilingual Chinese-English orthopaedic researcher.42 Two studies included patients

Discussion

The main findings of this systematic review were that multiple sequential intra-articular PRP knee injections (range of 2 to 4 injections) improved functional outcome scores (WOMAC and IKDC) at a minimum of 24 weeks. However, no benefit of PRP over control treatment was found for other pain measures (VAS) or overall patient satisfaction scores. Pooled comparisons using other common outcomes measures (e.g., Tegner scale,41 Knee Injury and Osteoarthritis Outcome Score,41 and an 11-point pain

Conclusions

As compared with HA or NS injection, multiple sequential intra-articular PRP injections may have beneficial effects in the treatment of adult patients with mild to moderate knee OA at approximately 6 months. There appears to be an increased incidence of nonspecific AEs among patients treated with PRP.

Acknowledgment

The authors thank Peggy Law, B.Sc., M.Sc., for her help with the Chinese-English translation.

References (90)

  • A.S. Detsky et al.

    Incorporating variations in the quality of individual randomized trials into metaanalysis

    J Clin Epidemiol

    (1992)
  • J. Chahal et al.

    The role of platelet-rich plasma in arthroscopic rotator cuff repair: A systematic review with quantitative synthesis

    Arthroscopy

    (2012)
  • C.C. Wu et al.

    Regenerative potentials of platelet-rich plasma enhanced by collagen in retrieving pro-inflammatory cytokine-inhibited chondrogenesis

    Biomaterials

    (2011)
  • K. Akeda et al.

    Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis

    Osteoarthritis Cartilage

    (2006)
  • G. Milano et al.

    Repeated platelet concentrate injections enhance reparative response of microfractures in the treatment of chondral defects of the knee: An experimental study in an animal model

    Arthroscopy

    (2012)
  • G. Milano et al.

    The effect of platelet rich plasma combined with microfractures on the treatment of chondral defects: An experimental study in a sheep model

    Osteoarthritis Cartilage

    (2010)
  • P. Harrison et al.

    Platelet alpha-granules

    Blood Rev

    (1993)
  • Y. Mifune et al.

    The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair

    Osteoarthritis Cartilage

    (2013)
  • P. Kasten et al.

    The effect of platelet-rich plasma on healing in critical-size long-bone defects

    Biomaterials

    (2008)
  • P. Niemeyer et al.

    Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma

    Biomaterials

    (2010)
  • M.B. Schmidt et al.

    A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair

    Osteoarthritis Cartilage

    (2006)
  • J. Richmond et al.

    American Academy of Orthopaedic Surgeons clinical practice guideline on the treatment of osteoarthritis (OA) of the knee

    J Bone Joint Surg Am

    (2010)
  • E.A. Rankin et al.

    NIH consensus statement on total knee replacement December 8-10, 2003

    J Bone Joint Surg Am

    (2004)
  • N. Maricar et al.

    Predictors of response to intra-articular steroid injections in knee osteoarthritis—A systematic review

    Rheumatology

    (2013)
  • N. Bellamy et al.

    Viscosupplementation for the treatment of osteoarthritis of the knee

    Cochrane Database Syst Rev

    (2006)
  • R.W. Brouwer et al.

    Braces and orthoses for treating osteoarthritis of the knee

    Cochrane Database Syst Rev

    (2005)
  • M. Fransen et al.

    Exercise for osteoarthritis of the knee

    Cochrane Database Syst Rev

    (2008)
  • E. Nuesch et al.

    Oral or transdermal opioids for osteoarthritis of the knee or hip

    Cochrane Database Syst Rev

    (2009)
  • T.E. Towheed et al.

    Glucosamine therapy for treating osteoarthritis

    Cochrane Database Syst Rev

    (2005)
  • S. Wandel et al.

    Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: Network meta-analysis

    BMJ

    (2010)
  • L.W. Moreland

    Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: Mechanisms of action

    Arthritis Res Ther

    (2003)
  • A.A. Brief et al.

    Use of glucosamine and chondroitin sulfate in the management of osteoarthritis

    J Am Acad Surg

    (2001)
  • A. Kirkley et al.

    A randomized trial of arthroscopic surgery for osteoarthritis of the knee

    N Engl J Med

    (2008)
  • J.N. Katz et al.

    Surgery versus physical therapy for a meniscal tear and osteoarthritis

    N Engl J Med

    (2013)
  • W. Laupaffarakasem et al.

    Arthroscopic debridement for knee osteoarthritis

    Cochrane Database Syst Rev

    (2008)
  • R.W. Brouwer et al.

    Osteotomy for treating knee osteoarthritis

    Cochrane Database Syst Rev

    (2007)
  • E.A. Balazs

    Analgesic effect of elastoviscous hyaluronan solutions and the treatment of arthritic pain

    Cells Tissues Organs

    (2003)
  • F. Cerza et al.

    Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis

    Am J Sports Med

    (2012)
  • E.J. Strauss et al.

    Hyaluronic acid viscosupplementation and osteoarthritis: Current uses and future directions

    Am J Sports Med

    (2009)
  • L.D. Kaplan et al.

    The effect of early hyaluronic acid delivery on the development of an acute articular cartilage lesion in a sheep model

    Am J Sports Med

    (2009)
  • N. Miyakoshi et al.

    Effects of intraarticular administration of basic fibroblast growth factor with hyaluronic acid on osteochondral defects of the knee in rabbits

    Arch Orthop Trauma Surg

    (2005)
  • P. Juni et al.

    Efficacy and safety of intraarticular hylan or hyaluronic acids for osteoarthritis of the knee—A randomized controlled trial

    Arthritis Rheum

    (2007)
  • J. Bernstein

    Therapeutic effects of hyaluronic acid on osteoarthritis of the knee

    J Bone Joint Surg Am

    (2004)
  • M.P. Curran

    Hyaluronic acid (Supartz): A review of its use in osteoarthritis of the knee

    Drugs Aging

    (2010)
  • R.E. Marx

    Platelet-rich plasma (PRP): What is PRP and what is not PRP?

    Implant Dent

    (2001)
  • Cited by (162)

    View all citing articles on Scopus

    The authors report the following potential conflict of interest or source of funding: T.L. and D.L. receive support from grants pending from Physicians Services Foundation Inc as Principal Investigator and grants received from Orthopaedic Trauma Association as both Principal Investigator and a co-investigator. J.T. receives support from Zimmer, Linvatec, and Smith & Nephew. R.G. receives support from Smith & Nephew.

    View full text