Purpose
To evaluate the effectiveness and explore the therapeutic mechanisms of platelet-rich
plasma (PRP) combined with hyaluronic acid (HA) as a treatment for knee osteoarthritis
(KOA).
Methods
In total, 122 knees were randomly divided into HA (34 knees), PRP (40 knees), and
PRP+HA (48 knees) groups. Platelet densities in whole blood and PRP were examined
using Wright–Giemsa staining. Visual analogue scale, Lequesne, Western Ontario and
McMaster Universities Osteoarthritis Index, Lysholm scores, and postoperative complications
were evaluated. High-frequency color Doppler imaging was used to observe the synovium
and cartilage. Enzyme-linked immunosorbent assays were used to quantify interleukin-1β,
tumor necrosis factor-α, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinase-1
levels in synovial fluid.
Results
The platelet density in PRP was 5.13-times that in whole blood (P = .002). At 24 months, pain and function scores in the PRP+HA group were better than
those in the HA-alone and PRP-alone groups (Ppain = .000; Pfunction = .000). At 6 and 12 months, synovial hyperplasia in the PRP and PRP+HA groups was
improved (P < .05). After 6 and 12 months, the synovial peak systolic velocity, synovial end-diastolic
velocity, systolic/diastolic ratio, and resistance index were improved in the PRP+HA
group (P < .05). Complications were greatest in the PRP group (P = .008). After 6 and 12 months, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-3,
and tissue inhibitor of metalloproteinase-1 in the PRP and PRP+HA groups decreased
(P < .05), with more apparent inhibition in the PRP+HA group (P < .05).
Conclusions
PRP combined with HA is more effective than PRP or HA alone at inhibiting synovial
inflammation and can effectively improve pain and function and reduce adverse reactions.
Its mechanism involves changes in the synovium and cytokine content.
Level of Evidence
Level II, Prospective cohort study.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to ArthroscopyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- The importance of subchondral bone in the pathophysiology of osteoarthritis.Front Vet Sci. 2018; 5: 178
- Platelet-rich plasma modulates actions on articular cartilage lubrication and regeneration.Tissue Eng Part B Rev. 2016; 22: 408-419
- Clinical outcomes are associated with changes in ultrasonographic structural appearance after platelet-rich plasma treatment for knee osteoarthritis.Int J Rheum Dis. 2018; 21: 960-966
- Risk factors of knee osteoarthritis—excellent evidence but little has been done.Osteoarthritis Cartilage. 2010; 18: 1-2
- Intra-articular ozone or hyaluronic acid injection: Which one is superior in patients with knee osteoarthritis? A 6-month randomized clinical trial.J Pain Res. 2018; 11: 111-117
- 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: 958-965
- Viscosupplementation for osteoarthritis of the knee: A systematic review of the evidence.J Bone Joint Surg Am. 2015; 97: 2047-2060
- Surgical treatment for early osteoarthritis. Part I: Cartilage repair procedures.Knee Surg Sports Traumatol Arthrosc. 2012; 20: 450-466
- The AAHKS Clinical Research Award: What are the costs of knee osteoarthritis in the year prior to total knee arthroplasty.J Arthroplasty. 2017; 32: S8-S10.e1
- Does timing of previous intra-articular steroid injection affect the post-operative rate of infection in total knee arthroplasty.J Arthroplasty. 2015; 30: 1879-1882
- The John N. Insall Award: Do intraarticular injections increase the risk of infection after TKA.Clin Orthop Relat Res. 2017; 475: 45-52
- platelet-rich plasma derived growth factors contribute to stem cell differentiation in musculoskeletal regeneration.Front Chem. 2017; 5: 89
- Human platelet-rich plasma induces chondrogenic differentiation of subchondral progenitor cells in polyglycolic acid-hyaluronan scaffolds.J Biomed Mater Res B Appl Biomater. 2014; 102: 681-692
- Autologous platelet-rich plasma promotes proliferation and chondrogenic differentiation of adipose-derived stem cells.Mol Med Rep. 2015; 11: 1298-1303
- Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage.Stem Cell Res Ther. 2013; 4: 91
- Platelet-rich plasma: Intra-articular knee injections produced favorable results on degenerative cartilage lesions.Knee Surg Sports Traumatol Arthrosc. 2010; 18: 472-479
- Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee.Knee Surg Sports Traumatol Arthrosc. 2016; 24: 1665-1677
- Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis: Preliminary results in a group of active patients.Sports Health. 2012; 4: 162-172
- Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: A randomized controlled trial.Arthroscopy. 2013; 29: 1635-1643
- Platelet-rich plasma shows beneficial effects for patients with knee osteoarthritis by suppressing inflammatory factors.Exp Ther Med. 2018; 15: 3096-3102
- Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee.J Stem Cells Regen Med. 2016; 12: 69-78
- Clinical therapy of hyaluronic acid combined with platelet-rich plasma for the treatment of knee osteoarthritis.Exp Ther Med. 2018; 16: 2119-2125
- Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy.Biomaterials. 2014; 35: 9599-9607
- Efficacy and safety profile of a compound composed of platelet-rich plasma and hyaluronic acid in the treatment for knee osteoarthritis (preliminary results).Eur J Orthop Surg Traumatol. 2015; 25: 1321-1326
- Clinical effectiveness in severe knee osteoarthritis after intra-articular platelet-rich plasma therapy in association with hyaluronic acid injection: three case reports.Clin Interv Aging. 2016; 11: 1213-1219
- Intra-articular hyaluronic acid (HA) and platelet rich plasma (PRP) injection versus hyaluronic acid (HA) injection alone in patients with Grade III and IV knee osteoarthritis (OA): A retrospective study on functional outcome.Malays Orthop J. 2016; 10: 35-40
- One-step osteochondral repair with cartilage fragments in a composite scaffold.Knee Surg Sports Traumatol Arthrosc. 2012; 20 (2590-s601)
- Platelet-rich plasma combined with injectable hyaluronic acid hydrogel for porcine cartilage regeneration: A 6-month follow-up.Regen Biomater. 2020; 7: 77-90
- Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: A systematic review and meta-analysis.BMC Musculoskelet Disord. 2020; 21: 224
- Optimization of pure platelet-rich plasma preparation: A comparative study of pure platelet-rich plasma obtained using different centrifugal conditions in a single-donor model.Exp Ther Med. 2017; 14: 2060-2070
- Intra-articular injection of platelet-rich plasma is superior to hyaluronic acid or saline solution in the treatment of mild to moderate knee osteoarthritis: A randomized, double-blind, triple-parallel, placebo-controlled clinical trial.Arthroscopy. 2019; 35: 106-117
- Quantitative evaluation of microvascular blood flow by contrast-enhanced ultrasound (CEUS).Clin Hemorheol Microcirc. 2011; 49: 137-149
- EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: Prevalence of inflammation in osteoarthritis.Ann Rheum Dis. 2005; 64: 1703-1709
- Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options.Knee Surg Sports Traumatol Arthrosc. 2017; 25: 485-492
- Intra-articular hylastan versus steroid for knee osteoarthritis.Knee Surg Sports Traumatol Arthrosc. 2014; 22: 1684-1692
- Intra-articular hyaluronic acid in treatment of knee osteoarthritis: A meta-analysis.JAMA. 2003; 290: 3115-3221
- Viscosupplementation for the treatment of osteoarthritis of the knee.Cochrane Database Syst Rev. 2006; 2: CD005321
- Effectiveness of platelet-rich plasma and hyaluronic acid for the treatment and care of pressure ulcers.Biol Res Nurs. 2015; 17: 152-158
- Use of platelet-rich plasma and hyaluronic acid in the loss of substance with bone exposure.Adv Skin Wound Care. 2011; 24: 176-181
- Regenerative surgery of the complications with Morton's neuroma surgery: Use of platelet rich plasma and hyaluronic acid.Int Wound J. 2013; 10: 372-376
- Cocktail of hyaluronic acid and human amniotic mesenchymal cells effectively repairs cartilage injuries in sodium iodoacetate-induced osteoarthritis rats.Front Bioeng Biotechnol. 2020; 8: 87
- Platelet-rich plasma: evidence to support its use.J Oral Maxillofac Surg. 2004; 62: 489-496
- Development of a rapid knee cartilage damage quantification method using magnetic resonance images.BMC Musculoskelet Disord. 2014; 15: 264
- Rates and sensitivity of knee cartilage thickness loss in specific central reading radiographic strata from the osteoarthritis initiative.Osteoarthritis Cartilage. 2014; 22: 1550-1553
- An update on risk factors for cartilage loss in knee osteoarthritis assessed using MRI-based semiquantitative grading methods.Eur Radiol. 2015; 25: 883-893
- Whole joint MRI assessment of surgical cartilage repair of the knee: cartilage repair osteoarthritis knee score (CROAKS).Osteoarthritis Cartilage. 2014; 22: 779-799
- Synovial changes detected by ultrasound in people with knee osteoarthritis—a meta-analysis of observational studies.Osteoarthritis Cartilage. 2016; 24: 1376-1383
- Association between ultrasound-detected synovitis and knee pain: A population-based case-control study with both cross-sectional and follow-up data.Arthritis Res Ther. 2017; 9: 281
- What drives osteoarthritis? Synovial versus subchondral bone pathology.Rheumatology (Oxford). 2017; 56: 1461-1471
- Role of inflammation in the pathogenesis of osteoarthritis: Latest findings and interpretations.Ther Adv Musculoskelet Dis. 2013; 5: 77-94
- Superb microvascular imaging in low-grade inflammation of knee osteoarthritis compared with power Doppler: Clinical, radiographic and MRI relationship.Ultrasound Med Biol. 2020; 46: 566-574
- Assessment of synovitis in the knee of patients with newly-diagnosed rheumatoid arthritis using high frequency and color Doppler ultrasonography.Zhonghua Yi Xue Za Zhi. 2011; 91: 1630-1632
- Synovial inflammation in patients with different stages of knee osteoarthritis.Rom J Morphol Embryol. 2015; 56: 169-173
- Synovitis in osteoarthritis: Current understanding with therapeutic implications.Arthritis Res Ther. 2017; 19: 18
- Change of chondral lesions and predictive factors after medial open-wedge high tibial osteotomy with a locked plate System.Am J Sports Med. 2017; 45: 1615-1621
- Second-look arthroscopic assessment of cartilage regeneration after medial opening-wedge high tibial osteotomy.Arthroscopy. 2014; 30: 72-79
- Medial compartment decompression by fibular osteotomy to treat medial compartment knee osteoarthritis: A pilot study.Orthopedics. 2015; 38 (:e1110-1104)
- Medial compartment decompression by proximal fibular osteotomy: A biomechanical cadaver study.Orthopedics. 2018; 41: e496-e501
- Open-wedge osteotomy using an internal plate fixator in patients with medial-compartment gonarthritis and varus malalignment: 3-year results with regard to preoperative arthroscopic and radiographic findings.Arthroscopy. 2010; 26: 1607-1616
- Growth factors levels determine efficacy of platelets rich plasma injection in knee osteoarthritis: A randomized double blind noninferiority trial compared with viscosupplementation.Arthroscopy. 2018; 34: 1530-1540.e2
- Role of low-grade inflammation in osteoarthritis.Curr Opin Rheumatol. 2017; 29: 79-85
- Interleukin-34 synovial fluid was associated with knee osteoarthritis severity: A cross-sectional study in knee osteoarthritis patients in different radiographic stages.Dis Marker. 2018; 2018: 2095480
- Rediscovering the therapeutic use of glucocorticoids in rheumatoid arthritis.Curr Opin Rheumatol. 2016; 28: 289-296
- Efficacy and safety of adalimumab by intra-articular injection for moderate to severe knee osteoarthritis: An open-label randomized controlled trial.J Int Med Res. 2018; 46: 326-334
- Isofraxidin inhibits interleukin-1β induced inflammatory response in human osteoarthritis chondrocytes.Int Immunopharmacol. 2018; 64: 238-245
Article info
Publication history
Published online: October 19, 2020
Accepted:
October 11,
2020
Received:
February 4,
2020
Footnotes
See commentary on page 916
The authors report that they have no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material.
Identification
Copyright
© 2020 by the Arthroscopy Association of North America
