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Sillmann YM, Monteiro JLGC, Haugstad M, Burris B, Keith DA, Handa S, Guastaldi FPS. Intra-articular injection of orthobiologics for temporomandibular joint osteoarthritis: a systematic review of randomized controlled trials. Int J Oral Maxillofac Surg 2025; 54:624-638. [PMID: 39890574 DOI: 10.1016/j.ijom.2025.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 01/03/2025] [Accepted: 01/09/2025] [Indexed: 02/03/2025]
Abstract
Temporomandibular joint (TMJ) osteoarthritis (OA) leads to pain, limited jaw function, and bite changes. When non-invasive treatments fail, minimally invasive procedures like TMJ arthrocentesis with saline and hyaluronic acid (HA) injections are commonly used. Orthobiologics, including platelet-rich plasma (PRP) and cell-derived products, have gained attention for their potential to enhance tissue healing. This review aimed to compare the outcomes of orthobiologic injections with HA injections following arthrocentesis in TMJ-OA treatment. A systematic search, following PRISMA guidelines, identified nine studies (403 patients). Risk of bias was assessed using the Cochrane Risk of Bias Tool. PRP and cell-derived products showed potential benefits in reducing TMJ pain and improving maximum mouth opening (MMO). However, three of four studies comparing PRP with HA found no significant difference between the two. In contrast, cell-derived orthobiologics demonstrated significantly greater improvements in TMJ pain and MMO compared to HA. Risk of bias varied, with some studies showing moderate to high levels. This review highlights the potential but inconsistent benefits of orthobiologics in treating TMJ-OA. While cell-derived orthobiologics appear promising, PRP did not demonstrate superiority over HA. Further high-quality studies are needed to validate these findings.
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Affiliation(s)
- Y M Sillmann
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA, USA; Harvard School of Dental Medicine, Boston, MA, USA
| | - J L G C Monteiro
- Wellman Center for Photomedicine, Harvard Medical School, Boston, MA, USA
| | - M Haugstad
- Harvard School of Dental Medicine, Boston, MA, USA
| | - B Burris
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA, USA; Harvard School of Dental Medicine, Boston, MA, USA
| | - D A Keith
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA, USA; Harvard School of Dental Medicine, Boston, MA, USA
| | - S Handa
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA, USA; Harvard School of Dental Medicine, Boston, MA, USA
| | - F P S Guastaldi
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, MA, USA; Harvard School of Dental Medicine, Boston, MA, USA.
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Fucaloro SP, Bragg J, Berhane M, Mulvey M, Krivicich L, Zink T, Salzler M. Complications of Platelet Rich Plasma Injection for Knee Osteoarthritis are Similar to Corticosteroids and Hyaluronic Acid, but are Significantly Greater than Placebo Injections: A Meta-Analysis of Randomized Controlled Trials. Arthroscopy 2025:S0749-8063(25)00373-1. [PMID: 40409439 DOI: 10.1016/j.arthro.2025.05.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 05/01/2025] [Accepted: 05/06/2025] [Indexed: 05/25/2025]
Abstract
PURPOSE The purpose of this review was to investigate complications of platelet rich plasma (PRP) injections for knee osteoarthritis (OA) compared to other injected substances including hyaluronic acid (HA), corticosteroids, and placebo saline. METHODS PubMed, Embase, Web of Science, and Cochrane databases were searched to identify randomized control trials (RCTs) comparing PRP to another injectable treatment for knee osteoarthritis with documented complications. Studies not mentioning complications or utilizing PRP during surgery were excluded. Complications were pooled to determine overall complication rate and the number needed to harm (NNH). Subgroup analyses were performed for studies comparing PRP to hyaluronic acid, corticosteroids, and placebo saline using DerSimonian-Laird random-effects models displaying odds ratios (OR). RESULTS Twenty-four RCTs were identified with 2751 total patients, 1318 of whom received PRP injections. There was a total of 246 complications in the PRP group and 131 in the comparison cohort (18.66% vs. 9.14%, respectively p < 0.01). The NNH was 11. Subgroup analysis showed no difference in odds of complications when PRP was compared to HA and corticosteroids (OR 1.33, p = 0.22 I2 = 0.0% and OR 3.07, p = 0.35, I2 = 63.49%, respectively), but significantly more complications compared to placebo (OR 4.88, p < 0.01, I2 = 0.00%). Only one patient reported severe pain; however all other complications were described as moderate or mild and self-limiting. CONCLUSION The use of PRP for knee OA is not innocuous with a significantly higher rate of complications compared to placebo. However, most complications were reported as mild to moderate, and the odds of complications are similar to that of HA or corticosteroid injections. Compared to all other injectables, the NNH for PRP is 11, which is important for physicians to consider prior to PRP therapy. LEVEL OF EVIDENCE Level II, meta-analysis of Level I and II RCTs.
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Affiliation(s)
- Stephen P Fucaloro
- Department of Orthopedic Surgery, Tufts Medical Center, Boston, MA; Tufts University School of Medicine, Boston, MA
| | - Jack Bragg
- Department of Orthopedic Surgery, Tufts Medical Center, Boston, MA
| | | | | | - Laura Krivicich
- Department of Orthopedic Surgery, Tufts Medical Center, Boston, MA
| | - Thomas Zink
- Department of Orthopedic Surgery, Tufts Medical Center, Boston, MA
| | - Matthew Salzler
- Department of Orthopedic Surgery, Tufts Medical Center, Boston, MA; Tufts University School of Medicine, Boston, MA.
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Peng YN, Peng YH, Chen JL, Chen CPC. Intraarticular leukocyte-poor platelet-rich plasma injection is more effective than intraarticular hyaluronic acid injection in the treatment of knee osteoarthritis: a systematic review and meta-analysis of 12 randomized controlled trials. Knee Surg Relat Res 2025; 37:15. [PMID: 40156001 PMCID: PMC11951639 DOI: 10.1186/s43019-025-00266-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 03/01/2025] [Indexed: 04/01/2025] Open
Abstract
PURPOSE We aim to compare the clinical effects of intraarticular leukocyte-poor platelet-rich plasma (LP-PRP) injection with those of intraarticular hyaluronic acid (HA) injection in adult patients with knee osteoarthritis. METHODS Two authors independently reviewed databases, including PubMed, Web of Science, and the Cochrane Library. Only randomized controlled trials (RCTs) were included in our meta-analysis. Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores (WOMAC total, pain, stiffness, and physical function scores), visual analog scale (VAS) scores, EQ-VAS scores, International Knee Documentation Committee (IKDC) scores, and adverse events were used as outcome measurements to evaluate the efficacy of LP-PRP and HA treatment. RESULTS After screening 377 potential articles, 12 RCTs were included in this systemic review and meta-analysis. The WOMAC total scores and WOMAC physical function scores of the LP-PRP group were better than those of the HA group at 6 and 12 months. VAS scores of the LP-PRP group were better than those of the HA group at 3, 6, and 12 months. The LP-PRP group showed a better outcome of IKDC scores than the HA group at 6 months. There was no significant difference in adverse events between the LP-PRP and HA groups. CONCLUSION Intraarticular injections of LP-PRP showed better overall outcomes, such as WOMAC total scores, WOMAC physical function scores, VAS scores, and IKDC scores, compared with HA for adult patients with knee osteoarthritis at 6- and 12-month follow-up periods. Also, LP-PRP showed better pain relief compared with HA at 3-, 6-, and 12-month follow-up periods. Intraarticular LP-PRP improves pain relief and overall outcomes in patients with knee osteoarthritis.
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Affiliation(s)
- Yu-Ning Peng
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Guishan District, Taoyuan City, Taiwan
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital 5 at Taoyuan, Chang Gung University, Fu-Hsin St., Kwei-Shan, Guishan District, Taoyuan City, 333, Taiwan
| | - Yu-Hsiang Peng
- Department of Medicine, MacKay Medical College, Sanzhi District, New Taipei City, Taiwan
| | - Jean-Lon Chen
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Guishan District, Taoyuan City, Taiwan
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital 5 at Taoyuan, Chang Gung University, Fu-Hsin St., Kwei-Shan, Guishan District, Taoyuan City, 333, Taiwan
| | - Carl P C Chen
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Guishan District, Taoyuan City, Taiwan.
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital 5 at Taoyuan, Chang Gung University, Fu-Hsin St., Kwei-Shan, Guishan District, Taoyuan City, 333, Taiwan.
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Xu H, Shi W, Liu H, Chai S, Xu J, Tu Q, Xu J, Zhuang W. Comparison of hyaluronic acid and platelet-rich plasma in knee osteoarthritis: a systematic review. BMC Musculoskelet Disord 2025; 26:236. [PMID: 40069655 PMCID: PMC11895219 DOI: 10.1186/s12891-025-08474-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 02/27/2025] [Indexed: 03/15/2025] Open
Abstract
BACKGROUND Knee osteoarthritis (KOA) is a common joint disorder, and intra-articular injections of hyaluronic acid (HA) or platelet-rich plasma (PRP) are frequently employed therapeutic interventions. However, there remains controversy regarding their efficacy. This systematic review aims to compare the effectiveness and safety of HA and PRP through a meta-analysis, with the objective of identifying the optimal treatment protocol for KOA and enhancing its management. METHODS Randomized controlled trials evaluating the clinical outcomes of patients receiving intra-articular injections of either HA or PRP were included as eligible studies. Two independent investigators assessed the selected studies and evaluated their risk of bias. Primary outcome measures included the Visual Analog Scale (VAS) score, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and other relevant assessment indices. Dichotomous variables were analyzed using risk ratios (RR) with 95% confidence intervals (CI). Data analysis was conducted using RevMan software (version 5.3). RESULTS A total of forty-two randomized controlled trials were included in this meta-analysis. No significant differences were observed between the patient populations in the two groups. The analysis demonstrated that PRP resulted in lower VAS and WOMAC scores compared to HA. Additionally, PRP exhibited superior performance across other evaluation indices. Notably, the incidence of adverse events was higher in the PRP group; however, all reported complications were mild. CONCLUSIONS Based on the current evidence, intra-articular injection of PRP appears to be more effective than HA for the treatment of KOA, as indicated by the analysis of VAS, WOMAC scores, and other evaluation indices. TRIAL REGISTRATION Retrospectively registered.
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Affiliation(s)
- Hong Xu
- Department of Orthopaedics, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China
| | - Weifeng Shi
- Department of Orthopaedics, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China
| | - Hong Liu
- Department of Orthopaedics, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China
| | - Shasha Chai
- Department of Orthopaedics, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China
| | - Jindi Xu
- Department of Orthopaedics, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China
- Zhejiang Chinese Medical University, Zhejiang Province, China
| | - Qingyu Tu
- Department of Orthopaedics, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China
- Zhejiang Chinese Medical University, Zhejiang Province, China
| | - Jinwei Xu
- Department of Orthopaedics, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China.
| | - Wei Zhuang
- Department of Orthopaedics, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China.
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Migliorini F, Maffulli N, Pipino G, Jeyaraman M, Ramasubramanian S, Jeyaraman N. Intra-articular injections of hyaluronic acid versus plasma rich in growth factors (PRGF) for knee osteoarthritis: a meta-analysis of randomised controlled trials : A meta-analysis. ORTHOPADIE (HEIDELBERG, GERMANY) 2025; 54:218-226. [PMID: 39964439 DOI: 10.1007/s00132-025-04615-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/03/2025] [Indexed: 02/28/2025]
Abstract
INTRODUCTION The present meta-analysis compared intra-articular injections of hyaluronic acid (HA) versus plasma rich in growth factors (PRGF) in patients with knee osteoarthritis (OA). The outcome of interest was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). METHODS This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses: the 2020 PRISMA statement. All the head-to-head randomised controlled trials (RCT) comparing intra-articular HA injections versus PRGF were accessed and included in the present study. Only studies that clearly stated that injections were performed in patients with knee OA, irrespective of the severity of OA, were considered. Data concerning the WOMAC index were retrieved at baseline and last follow-up. The endpoint of interest was to investigate whether intra-articular HA injections are associated with WOMAC score improvement compared to PRGF injections at 4-6 months follow-up. RESULTS Data from 432 patients were collected and 76.3% (330 of 432) of the patients were women. The mean age of the patients was 58.2 ± 1.5 years and the mean body mass index (BMI) was 28.0 ± 0.5 kg/m2. At baseline, comparability in mean age, BMI, male:female ratio, WOMAC and related subscales were documented. The PRGF group evidenced lower values of the function subscale of the WOMAC index (P = 0.03). No difference was found in the overall WOMAC index (P = 0.05) and its stiffness (P = 0.4) and pain (P = 0.07) subscales. CONCLUSION The current level I evidence suggests that the use of PRGF might be associated with more favorable clinical outcomes than using HA.
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Affiliation(s)
- Filippo Migliorini
- Department of Orthopaedic and Trauma Surgery, Academic Hospital of Bolzano (SABES-ASDAA), 39100, Bolzano, Italy.
- Department of Life Sciences, Health, and Health Professions, Link Campus University, 00165, Rome, Italy.
| | - Nicola Maffulli
- Department of Trauma and Orthopaedic Surgery, Faculty of Medicine and Psychology, University La Sapienza, 00185, Roma, Italy
- School of Pharmacy and Bioengineering, Keele University Faculty of Medicine, ST4 7QB, Stoke on Trent, UK
- Centre for Sports and Exercise Medicine, Barts and the London School of Medicine and Dentistry, Mile End Hospital, Queen Mary University of London, E1 4DG, London, UK
| | - Gennaro Pipino
- Department of Orthopaedic and Trauma Surgery, Villa Erbosa Hospital, San Raffaele University, Bologna, Italy
| | - Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, 600077, Chennai, Tamil Nadu, India
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, 600002, Chennai, Tamil Nadu, India
| | - Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, 600077, Chennai, Tamil Nadu, India
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Anz AW, Branch EA, Jordan SE, Ostrander RV, Kindle BJ, Presley JC, Hackel JG, Maggi E, Plummer HA. Preoperative Platelet-Rich Plasma Injections Decrease Inflammatory and Chondrodegenerative Biomarkers in Patients With Acute Anterior Cruciate Ligament Tears: A Pilot Randomized Controlled Trial. Orthop J Sports Med 2025; 13:23259671241312754. [PMID: 40052182 PMCID: PMC11881934 DOI: 10.1177/23259671241312754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 09/04/2024] [Indexed: 03/09/2025] Open
Abstract
Background Posttraumatic osteoarthritis occurs at an alarming rate after anterior cruciate ligament (ACL) injury and reconstruction (ACLR). Purpose/Hypothesis The purpose of this pilot randomized controlled trial was to evaluate the preoperative effect of a 2-injection series of platelet-rich plasma (PRP) on the progression of inflammatory and chondrodegenerative biomarkers before ACLR. It was hypothesized that preoperative PRP injections would decrease the chondrotoxicity of the presurgical knee fluid. Study Design Randomized controlled trial; Level of evidence, 1. Methods A total of 24 participants were randomized to either a control or an intervention group. Both groups received joint aspirations within the first 10 days after ACL injury (visit 1). In addition to joint aspiration at visit 1, the PRP group received a leukocyte-poor, nonactivated PRP injection at visit 1 and an additional PRP injection 5 to 12 days after the initial visit (visit 2). Joint fluid samples were harvested in both groups at the time of ACLR (visit 3). The joint fluid and PRP samples were subject to inflammatory and chondrodegenerative biomarker analysis for the following: interleukin (IL)-1ß, IL-10, IL-6, granulocyte-macrophage colony-stimulating factor, IL-5, interferon (IFN)-γ, tumor necrosis factor-α, IL-2, IL-4, and IL-8. Results The final analysis was completed on 8 participants in the control group and 8 in the intervention group. At visit 1, no significant differences were observed in cytokine concentrations between the control and intervention groups. Between visits 1 and 3, the control group demonstrated significant decreases in IL-8 (P = .007) and IFN-γ (P = .007), whereas the intervention group demonstrated significant decreases in all cytokine concentrations (P < .05) except for IL-8 (P = .08). At visit 3, similar to visit 1, no significant group differences were observed in cytokine concentrations. The PRP products in the intervention group were analyzed using complete blood counts and were consistent with defined concentrations found in leukocyte-poor PRP product. Conclusion Intervention with aspiration combined with a 2-injection series of leukocyte-poor PRP in the acute ACL-injured knee resulted in a significant reduction in effusion inflammatory markers, whereas the control aspiration (without PRP injections) did not show such marker reduction. Registration NCT04088227 (ClinicalTrials.gov identifier).
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Affiliation(s)
- Adam W. Anz
- Department of Research, Andrews Institute Center for Regenerative Medicine, Andrews Research & Education Foundation (AREF), Gulf Breeze, Florida, USA
| | - Eric A. Branch
- Department of Research, Andrews Institute Center for Regenerative Medicine, Andrews Research & Education Foundation (AREF), Gulf Breeze, Florida, USA
| | - Steve E. Jordan
- Department of Research, Andrews Institute Center for Regenerative Medicine, Andrews Research & Education Foundation (AREF), Gulf Breeze, Florida, USA
| | - Roger V. Ostrander
- Department of Research, Andrews Institute Center for Regenerative Medicine, Andrews Research & Education Foundation (AREF), Gulf Breeze, Florida, USA
| | - Brett J. Kindle
- Department of Research, Andrews Institute Center for Regenerative Medicine, Andrews Research & Education Foundation (AREF), Gulf Breeze, Florida, USA
| | - James C. Presley
- Department of Research, Andrews Institute Center for Regenerative Medicine, Andrews Research & Education Foundation (AREF), Gulf Breeze, Florida, USA
| | - Joshua G. Hackel
- Department of Research, Andrews Institute Center for Regenerative Medicine, Andrews Research & Education Foundation (AREF), Gulf Breeze, Florida, USA
| | - Emily Maggi
- Department of Research, Andrews Institute Center for Regenerative Medicine, Andrews Research & Education Foundation (AREF), Gulf Breeze, Florida, USA
| | - Hillary A. Plummer
- Department of Research, Andrews Institute Center for Regenerative Medicine, Andrews Research & Education Foundation (AREF), Gulf Breeze, Florida, USA
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Budhiparama NC, Putramega D, Lumban-Gaol I. Orthobiologics in knee osteoarthritis, dream or reality? Arch Orthop Trauma Surg 2024; 144:3937-3946. [PMID: 38630251 PMCID: PMC11564396 DOI: 10.1007/s00402-024-05310-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 03/24/2024] [Indexed: 11/15/2024]
Abstract
Cartilage restoration or repair, also known as orthobiologic therapy, is indicated after the failure of conservative or supportive treatment. However, there is paucity in evidence supporting the efficacy of orthobiologic therapy. The blood-derived products, such as platelet-rich plasma (PRP), is one of the commonly used orthobiologic therapy for knee osteoarthritis. Several studies have shown that PRP is superior to other treatments, but the anatomic changes are scarce. Treatment with mesenchymal stem cells (MSCs) offers the greatest potential for curing degenerative disease due to their self-renewal ability, ability to migrate towards injured tissues (homing/trafficking), and ability to promote repair and regeneration of osteochondral defects. However, ethical concerns and high costs remain major challenges associated with MSC therapy. Gene therapy, another promising orthobiologic therapy, is currently in phase II clinical trial and has shown promising results. The key factors for successful orthobiologic therapy include patient selection, appropriate dosing, treatment of underlying mechanical problems, age, severity, and cost-effectiveness.
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Affiliation(s)
- Nicolaas Cyrillus Budhiparama
- Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
- Department of Orthopaedic and Traumatology, Faculty of Medicine, Universitas Airlangga, Jl. Mayjend. Prof. Dr. Moestopo 6-8, Surabaya, 60286, Indonesia.
- Nicolaas Institute of Constructive Orthopaedic Research & Education Foundation for Arthroplasty & Sports Medicine at Medistra Hospital, Jl. Jend. Gatot Subroto Kav. 59, Jakarta, 12950, Indonesia.
| | - Dananjaya Putramega
- Nicolaas Institute of Constructive Orthopaedic Research & Education Foundation for Arthroplasty & Sports Medicine at Medistra Hospital, Jl. Jend. Gatot Subroto Kav. 59, Jakarta, 12950, Indonesia
- Academic Hospital Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Imelda Lumban-Gaol
- Nicolaas Institute of Constructive Orthopaedic Research & Education Foundation for Arthroplasty & Sports Medicine at Medistra Hospital, Jl. Jend. Gatot Subroto Kav. 59, Jakarta, 12950, Indonesia
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Yoshioka T, Arai N, Sugaya H, Taniguchi Y, Kanamori A, Gosho M, Okuno K, Kikuchi N, Hyodo K, Aoto K, Yamazaki M. The Effectiveness of Leukocyte-Poor Platelet-Rich Plasma Injections for Symptomatic Mild to Moderate Osteoarthritis of the Knee With Joint Effusion or Bone Marrow Lesions in a Japanese Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Am J Sports Med 2024; 52:2493-2502. [PMID: 39097760 DOI: 10.1177/03635465241263073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/05/2024]
Abstract
BACKGROUND Intra-articular platelet-rich plasma (PRP) injections have been proposed for the treatment of knee osteoarthritis (OA); however, their effectiveness in Japanese patients remains unclear. PURPOSE To investigate whether 3 intra-articular injections of leukocyte-poor PRP (LP-PRP) improve symptoms and joint function in symptomatic Japanese patients with mild to moderate knee OA. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS Of 72 patients screened, 30 were included and randomized to receive LP-PRP (n = 15) or saline (placebo; n = 15) injections between March 2019 and February 2023. Patients attended a screening visit and 3 treatment visits at 1 week apart, followed by 3 follow-up visits (at 4, 12, and 24 weeks) after the initial treatment visit. The primary efficacy outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, whereas the secondary efficacy outcome measures were the proportion of patients showing a visual analog scale (VAS) improvement of ≥50%. Magnetic resonance imaging was performed to evaluate joint effusion and bone marrow lesions using the Whole-Organ Magnetic Resonance Imaging Score. Patients were followed for 24 weeks. RESULTS Patients in the PRP group (mean age, 65.9 years) had a mean hip-knee-ankle angle of 5.1°, with 7 and 8 patients demonstrating Kellgren-Lawrence grade 2 and 3 knee OA, respectively. Patients in the placebo group (mean age, 67.9 years) had a mean hip-knee-ankle angle of 3.8°, with 6 and 9 patients showing Kellgren-Lawrence grade 2 and 3 knee OA, respectively. No significant differences were identified in any baseline factors. The percentage change in Western Ontario and McMaster Universities Osteoarthritis Index scores from baseline to 24 weeks was significantly different (P= .032) between the PRP (median, 75.9%; quantile 1 [Q1], 49.6; quantile 3 [Q3], 94.1]) and placebo (median, 27.7%; Q1, -9.4; Q3, 80.9]) groups. Overall, 73.3% and 28.6% of the PRP group and placebo group, respectively, exhibited an improvement in visual analog scale scores of ≥50%, with a significant improvement observed in the PRP group (P = .027). Changes in bone marrow lesions from baseline to 24 weeks, as assessed on magnetic resonance imaging, significantly differed between groups (P = .017), with no significant differences in other secondary endpoints. CONCLUSION In Japanese patients with knee OA, 3 intra-articular LP-PRP injections led to clinical improvements at 24-week follow-up and significant functional improvements and pain relief after 24 weeks.
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Affiliation(s)
- Tomokazu Yoshioka
- Division of Regenerative Medicine, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Norihito Arai
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Hisashi Sugaya
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Yu Taniguchi
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Akihiro Kanamori
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Masahiko Gosho
- Department of Biostatistics, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kosuke Okuno
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Naoya Kikuchi
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kojiro Hyodo
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Katsuya Aoto
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Masashi Yamazaki
- Department of Orthopedic Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
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Vaquerizo V. Author Reply: Update the Dosing Frequency of Injections of PRGF-Endoret for the Treatment of Knee Osteoarthritis. Arthroscopy 2024; 40:1956-1957. [PMID: 38537728 DOI: 10.1016/j.arthro.2024.03.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 03/20/2024] [Indexed: 04/17/2024]
Affiliation(s)
- Victor Vaquerizo
- Principe de Asturias University Hospital, Alcalá de Henares, Madrid, Spain
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Gupta A. Efficacy of Plasma Rich in Growth Factors for the Treatment of Knee Osteoarthritis. Arthroscopy 2024; 40:1956. [PMID: 38537723 DOI: 10.1016/j.arthro.2024.03.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 03/20/2024] [Indexed: 04/17/2024]
Affiliation(s)
- Ashim Gupta
- Future Biologics, Lawrenceville, Georgia, U.S.A.; South Texas Orthopaedic Research Institute, STORI Inc., Laredo, Texas, U.S.A.; Regenerative Orthopaedics, Noida, India
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Abu-Awwad A, Tudoran C, Abu-Awwad SA, Tudoran M, Voita-Mekeres F, Faur C, Szilagyi G. Analogies Between Platelet-Rich Plasma Versus Hyaluronic Acid Intra-articular Injections in the Treatment of Advanced Knee Arthritis: A Single-Center Study. Cureus 2024; 16:e61163. [PMID: 38933627 PMCID: PMC11202161 DOI: 10.7759/cureus.61163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2024] [Indexed: 06/28/2024] Open
Abstract
Background Knee osteoarthritis (KOA), a degenerative joint disease, is a common cause of chronic knee pain and disability in adults. Conservative management options are the first-line approach, but intra-articular injections, such as platelet-rich plasma (PRP) and hyaluronic acid (HA), are considered for advanced cases. This study aims to compare the efficacy of PRP versus HA injections in patients with advanced KOA. Methods A retrospective study was conducted on 145 patients with advanced KOA. Seventy patients received PRP injections, while 75 patients received HA injections. The Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and International Knee Documentation Committee (IKDC) score were employed to evaluate the treatment's efficacy. Adverse events associated with these injections were also recorded. Results Both PRP and HA injections significantly reduced pain and improved joint function in patients with advanced KOA. PRP injections were slightly more effective than HA injections in reducing pain scores. Both treatments showed similar improvements in functional outcomes. Adverse events were minimal and self-limiting for both treatments. Conclusions Both PRP and HA injections effectively ameliorate advanced KOA by reducing pain and improving function. PRP injections showed a slightly greater improvement in pain scores and functional outcomes. The choice between PRP and HA injections may depend on factors like cost, availability, and patient preference. Further research is needed to validate these findings and understand treatment suitability for different patient populations.
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Affiliation(s)
- Ahmed Abu-Awwad
- Orthopedics and Traumatology, Department XV-Discipline of Orthopedics-Traumatology, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, ROU
- Orthopedics and Traumatology, "Pius Brinzeu" County Emergency Hospital, Timisoara, ROU
- Orthopedics and Traumatology, Research Center University Professor Doctor Teodor Șora, Victor Babes University of Medicine and Pharmacy, Timisoara, ROU
| | - Cristina Tudoran
- Department VII, Internal Medicine II, Discipline of Cardiology, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, ROU
- Cardiology, Center of Molecular Research in Nephrology and Vascular Disease, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, ROU
- Cardiology, "Pius Brinzeu" County Emergency Hospital, Timisoara, ROU
| | - Simona-Alina Abu-Awwad
- Gynecology, "Pius Brinzeu" County Emergency Hospital, Timisoara, ROU
- Gynecology, Department XII-Discipline of Obstetrics and Gynecology, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, ROU
| | - Mariana Tudoran
- Cardiology, "Pius Brinzeu" County Emergency Hospital, Timisoara, ROU
| | - Florica Voita-Mekeres
- Morphological Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, ROU
| | - Cosmin Faur
- Orthopedics and Traumatology, Department XV-Discipline of Orthopedics-Traumatology, Victor Babes University of Medicine and Pharmacy Timisoara, Timisoara, ROU
- Orthopedics and Traumatology, "Pius Brinzeu" County Emergency Hospital, Timisoara, ROU
- Orthopedics and Traumatology, Research Center University Professor Doctor Teodor Șora, Victor Babes University of Medicine and Pharmacy, Timisoara, ROU
| | - Gheorghe Szilagyi
- Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, ROU
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Dubin J, Leucht P, Murray M, Pezold R. American Academy of Orthopaedic Surgeons Technology Overview Summary: Platelet-Rich Plasma (PRP) for Knee Osteoarthritis. J Am Acad Orthop Surg 2024; 32:296-301. [PMID: 38295392 DOI: 10.5435/jaaos-d-23-00957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 11/09/2023] [Indexed: 02/02/2024] Open
Abstract
The Platelet-Rich Plasma (PRP) for Knee Osteoarthritis Technology Overview is based on a systematic review of current scientific and clinical research. Through analysis of the current best evidence, this technology overview seeks to evaluate the efficacy of PRP for patients with knee osteoarthritis. The systematic literature review resulted in 54 articles: 36 high-quality and 18 moderate-quality. The findings of these studies were summarized to present findings on PRP versus control/placebo, acetaminophen, non-steroidal anti-inflammatory drugs, corticosteroids, exercise, prolotherapy, autologous conditioned serum, bone marrow aspirate concentrate, hyaluronic acid, and ozone therapy. In addition, the work group highlighted areas that needed additional research when evidence proved lacking on the topic and carefully noted the potential harms associated with an intervention, required resource utilization, acceptability, and feasibility.
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Affiliation(s)
- Jonathan Dubin
- Truman Medical Center, University of Missouri, Columbia, MO (Dubin), Departments of Orthopaedic Surgery and Cell Biology, New York University School of Medicine, NYU Langone Health, New York, NY (Leucht), Harvard Medical School, Boston Children's Hospital, Boston, MA (Murray), American Academy of Orthopaedic Surgeons, Rosemont, IL (Pezold)
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Mohammed Abdulwahab D, Abdul Lateef SAA, Faris W, Rasheed Al Radhwany YAR. Single Shot of Knee Intraarticular Injection of Platelets Rich Plasma versus Hyaluronic Acid Injections for Symptomatic Knee Osteoarthritis. An Observational Prospective Study. INTERNATIONAL JOURNAL OF DISABILITIES SPORTS AND HEALTH SCIENCES 2024; 7:342-350. [DOI: 10.33438/ijdshs.1389727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The aim of this study was to evaluate the effectiveness and safety of intra-articular PRP and HA in KOA patients. Methods: The current work was prospective randomized observational. Participants were divided into two groups. Group 1; 1 intra-articular PRP injection (15 mL) in 72 patients and Group 2; A single intra-articular injection of HA (80 mg/4 mL) was administered to 72 patients. All patients were evaluated before infiltration and 1, 3, 6, and 12 months after injection. Results: No significant difference was detected in the demographic distribution (gender and age) and Grade RT, Grade RL, Grade II OA and Grade III OA classifications of patients who received intra-articular PRP or HA injection for knee OA (p>0.05). Compared with the HA group WOMAC mean of 48.8 and p<0.05, there was no significant change in the PRP groups with the WOMAC mean of 68.9. At month 3, each group had significantly reduced overall WOMAC score compared to baselines in both groups. The mean WOMAC was 48.2 in the HA and 47.9 in the PRP group (P<0.001). At 6 months, the average WOMAC score of the PRP group was 39.4, while this rate was 56.3 in the HA group (P<0.001). The PRP group showed a steady improvement, while those treated with HA showed a rapid deterioration. At 12 months, the HA group's WOMAC scores (74.1) returned to baseline levels. The mean WOMAC of the PRP group was (58.9) (P<0.001). Conclusion: The overall PRP improvement outweighs HA injections
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Affiliation(s)
| | | | - Waleed Faris
- orthopedic surgeon Department of surgery, Iraqia Med school
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14
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Khalid S, Ali A, Deepak FNU, Zulfiqar MS, Malik LU, Fouzan Z, Nasr RA, Qamar M, Bhattarai P. Comparative effectiveness of intra-articular therapies in knee osteoarthritis: a meta-analysis comparing platelet-rich plasma (PRP) with other treatment modalities. Ann Med Surg (Lond) 2024; 86:361-372. [PMID: 38222750 PMCID: PMC10783230 DOI: 10.1097/ms9.0000000000001615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/03/2023] [Indexed: 01/16/2024] Open
Abstract
INTRODUCTION Knee osteoarthritis (KOA) is a progressive joint disease commonly treated with intra-articular injections, including platelet-rich plasma (PRP), hyaluronic acid (HA), or corticosteroids (CS). This updated meta-analysis aims to enhance the statistical power of the results and provide comprehensive clinical evidence that reflects the most current research. By doing so, the authors aim to suggest a reliable estimate for the development of guidelines, addressing the pressing need for effective and minimally invasive treatment options. METHODS PubMed, Scopus, clinicaltrials.gov, Cochrane Central were searched until March 2023, for randomized controlled trials (RCTs) comparing the effectiveness of intra-articular injectable therapies, including PRP, HA, CS, and placebo, in KOA. Data extraction involved baseline characteristics and outcome measures [Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Visual Analog Scale (VAS) pain scores, KOOS, and IKDC scores] at 1, 3, 6 and 12 months. Statistical analysis, including subgroup analysis, assessment of heterogeneity, and publication bias, was conducted using Review Manager. RESULTS Our meta-analysis of 42 studies involving 3696 patients demonstrated that PRP treatment resulted in significant pain relief compared to HA injections, as evidenced by improved WOMAC pain (MD: -0.74; 95% CI: -1.02 to -0.46; P≤0.00001; I 2=94%) and VAS pain (MD: -0.65; 95% CI: -1.24 to -0.06; P=0.03; I2=97%) outcomes. Similarly, PRP showed greater efficacy in reducing WOMAC pain (MD: -8.06; 95% CI: -13.62 to -2.51: P=0.004; I 2=96%) and VAS pain (MD: -1.11; 95% CI: -1.64 to -0.59; P≤0.0001; I 2=68%) compared to CS injections, with the most significant improvement observed at 6 months. CONCLUSIONS PRP is an effective treatment for KOA. It provides symptomatic relief, has the potential to reduce disease progression, and has sustained effects up to 12 months. PRP offers superior pain relief and functional enhancement compared to CS and HA injections.
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Affiliation(s)
- Saad Khalid
- Department of Medicine, Dow University of Health Sciences
| | - Abraish Ali
- Department of Medicine, Dow University of Health Sciences
| | - FNU Deepak
- Shaheed Mohtarma Benazir Bhutto Medical College Lyari
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15
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Tao X, Aw AAL, Leeu JJ, Bin Abd Razak HR. Three Doses of Platelet-Rich Plasma Therapy Are More Effective Than One Dose of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis. Arthroscopy 2023; 39:2568-2576.e2. [PMID: 37236291 DOI: 10.1016/j.arthro.2023.05.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 05/04/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023]
Abstract
PURPOSE To compare the efficacy of a single dose of platelet-rich plasma (PRP) with multiple doses of PRP therapy in the treatment of knee osteoarthritis (KOA). METHODS The PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, and Cochrane Library databases were searched from database inception to May 2022; in addition, the gray literature and bibliographic references were searched. Only randomized controlled trials comparing the effect of a single dose versus multiple doses of PRP for KOA were included. Literature retrieval and data extraction were conducted by 3 independent reviewers. The inclusion and exclusion criteria were based on type of study, research subjects, intervention, outcome, language, and availability of data. Pooled analyses of visual analog scale (VAS) scores, Western Ontario and McMaster Universities Arthritis Index scores, and adverse events were conducted. RESULTS Seven studies (all randomized controlled trials) of high methodologic quality involving 575 patients were included. The ages of the patients included in this study ranged from 20 to 80 years, and the sex ratio was balanced. Triple-dose PRP therapy resulted in significantly better VAS scores compared with single-dose PRP therapy at 12 months (P < .0001), with no significant change in VAS scores between double-dose PRP and single-dose PRP at 12 months. Regarding adverse events, double-dose (P = .28) and triple-dose (P = .24) therapy showed no significant differences in safety from single-dose therapy. CONCLUSIONS Although there is a paucity of large high-quality Level I studies, current best evidence suggests that 3 doses of PRP for KOA are more effective than 1 dose of PRP at providing pain relief up to 1 year after administration. LEVEL OF EVIDENCE Level II, systematic review of Level II studies.
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Affiliation(s)
- Xinyu Tao
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Angeline Ai Ling Aw
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Jun Jie Leeu
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Hamid Rahmatullah Bin Abd Razak
- Department of Orthopaedic Surgery, Sengkang General Hospital, Singapore, Singapore; SingHealth Duke-NUS Musculoskeletal Sciences Academic Clinical Programme, Singapore, Singapore.
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16
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Ta CN, Vasudevan R, Mitchell BC, Keller RA, Kent WT. The Influence of Industry Affiliation on Randomized Controlled Trials of Platelet-Rich Plasma for Knee Osteoarthritis. Am J Sports Med 2023; 51:3583-3590. [PMID: 36594496 PMCID: PMC10623604 DOI: 10.1177/03635465221140917] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 09/23/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND Industry funding and corporate sponsorship have played a significant role in the advancement of orthopaedic research and technology. However, this relationship raises concerns for how industry association may bias research findings and influence clinical practice. PURPOSE To determine whether industry affiliation plays a role in the outcomes of randomized controlled trials (RCTs) investigating platelet-rich plasma (PRP). STUDY DESIGN Meta-analysis; Level of evidence, 2. METHODS A search of the PubMed, Cochrane, and MEDLINE databases for RCTs published between 2011 and the present comparing PRP versus hyaluronic acid, corticosteroid, or placebo for the treatment of knee osteoarthritis was performed. To determine industry affiliation, the conflict of interest, funding, and disclosure sections of publications were assessed, and all authors were assessed through the American Academy of Orthopaedic Surgeons disclosure database and the Centers for Medicare & Medicaid Services open payments database. Studies were classified as industry affiliated (IA) or non-industry affiliated (NIA). The outcomes of each study were rated as favorable, analogous, or unfavorable according to predefined criteria. RESULTS A total of 37 studies (6 IA and 31 NIA) were available for analysis. Overall, 19 studies (51.4%) reported PRP as favorable compared with other treatment options, while 18 studies (48.6%) showed no significant differences between PRP and other treatment methods. There was no significant difference in qualitative conclusions between the IA and NIA groups, with the IA group having 3 favorable studies and 3 analogous studies and the NIA group having 16 favorable studies and 15 analogous studies (P = .8881). When comparing IA versus NIA studies using 6- and 12-month Western Ontario and McMaster Universities Arthritis Index and International Knee Documentation Committee scores, there were no significant differences in outcomes. CONCLUSION The results of this study demonstrated that qualitative conclusions and outcome scores were found to not be associated with industry affiliation. Although the results of this study suggest that there is no influence of industry involvement on RCTs examining PRP, it is still necessary to carefully evaluate pertinent commercial affiliations when reviewing recommendations from studies before adopting new treatment approaches, such as the use of PRP for knee osteoarthritis.
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Affiliation(s)
- Canhnghi N. Ta
- Department of Orthopaedic Surgery, University of California, San Diego, San Diego, California, USA
| | - Rajiv Vasudevan
- School of Medicine, University of California, San Diego, San Diego, California, USA
| | - Brendon C. Mitchell
- Department of Orthopaedic Surgery, University of California, San Diego, San Diego, California, USA
| | | | - William T. Kent
- Department of Orthopaedic Surgery, University of California, San Diego, San Diego, California, USA
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17
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Bai MY, Vy VPT, Tang SL, Hung TNK, Wang CW, Liang JY, Wong CC, Chan WP. Current Progress of Platelet-Rich Derivatives in Cartilage and Joint Repairs. Int J Mol Sci 2023; 24:12608. [PMID: 37628786 PMCID: PMC10454586 DOI: 10.3390/ijms241612608] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 08/04/2023] [Accepted: 08/05/2023] [Indexed: 08/27/2023] Open
Abstract
In recent years, several types of platelet concentrates have been investigated and applied in many fields, particularly in the musculoskeletal system. Platelet-rich fibrin (PRF) is an autologous biomaterial, a second-generation platelet concentrate containing platelets and growth factors in the form of fibrin membranes prepared from the blood of patients without additives. During tissue regeneration, platelet concentrates contain a higher percentage of leukocytes and a flexible fibrin net as a scaffold to improve cell migration in angiogenic, osteogenic, and antibacterial capacities during tissue regeneration. PRF enables the release of molecules over a longer period, which promotes tissue healing and regeneration. The potential of PRF to simulate the physiology and immunology of wound healing is also due to the high concentrations of released growth factors and anti-inflammatory cytokines that stimulate vessel formation, cell proliferation, and differentiation. These products have been used safely in clinical applications because of their autologous origin and minimally invasive nature. We focused on a narrative review of PRF therapy and its effects on musculoskeletal, oral, and maxillofacial surgeries and dermatology. We explored the components leading to the biological activity and the published preclinical and clinical research that supports its application in musculoskeletal therapy. The research generally supports the use of PRF as an adjuvant for various chronic muscle, cartilage, and tendon injuries. Further clinical trials are needed to prove the benefits of utilizing the potential of PRF.
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Affiliation(s)
- Meng-Yi Bai
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan
- Adjunct Appointment to the Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan
| | - Vu Pham Thao Vy
- International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan;
- Department of Radiology, Thai Nguyen National Hospital, Thai Nguyen 24000, Vietnam
| | - Sung-Ling Tang
- Department of Pharmacy Practice, Tri-Service General Hospital, Taipei 11490, Taiwan
| | | | - Ching-Wei Wang
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan
| | - Jui-Yuan Liang
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Chin-Chean Wong
- Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan;
- Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11011, Taiwan
- International Ph.D. Program for Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei 11011, Taiwan
| | - Wing P. Chan
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Department of Radiology, Wan Fang Hospital, Taipei Medical University, Taipei 116081, Taiwan
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18
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Chan JP, Vrla M, Thompson C, Trofa DP, Li X, Wang D, Parisien RL. Statistical Fragility of Randomized Controlled Trials Evaluating Platelet-Rich Plasma Use for Knee Osteoarthritis: A Systematic Review. Orthop J Sports Med 2023; 11:23259671231187894. [PMID: 37655254 PMCID: PMC10467394 DOI: 10.1177/23259671231187894] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 04/13/2023] [Indexed: 09/02/2023] Open
Abstract
Background Numerous studies have been published on the use of platelet-rich plasma (PRP) for knee osteoarthritis (OA), with conflicting results. Purpose To determine the fragility index (FI) and fragility quotient (FQ) of randomized controlled trials (RCTs) that evaluated the use of PRP to treat knee OA. Study Design Systematic review. Methods RCTs evaluating the efficacy of PRP injections for knee OA from 2000 to 2020 were included for analysis according to PRISMA guidelines. The FI was determined by calculating the number of outcome event reversals required to change the statistical significance. The associated FQ was determined by dividing the FI by the sample size. Results Our initial search resulted in 41,149 studies, of which 8 RCTs (678 patients, 72 outcome events) were included in the analysis. One study failed to report PRP formulation details, whereas 87.5% of studies reported using either leukocyte-rich or leukocyte-poor PRP. The platelet concentration was reported in 25% of the included trials. The overall FI of the 72 outcome events was 8.5. Accounting for sample size, the associated FQ was determined to be 0.14, suggesting that the reversal of 14% of outcome events was required to change outcome significance. There were 51 statistically significant outcomes, of which the FI and FQ were 12 and 0.164, respectively. Conclusion Comprehensive fragility analysis suggested that the published literature evaluating the efficacy of PRP use for knee OA may lack statistical stability. We recommend the reporting of both an FI and FQ in addition to P value analysis to provide a clear and thorough understanding of the statistical integrity of studies reporting on PRP use for knee OA.
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Affiliation(s)
- Justin P Chan
- Department of Orthopaedic Surgery, University of California, Irvine, Irvine, California, USA
| | - Michael Vrla
- Department of Orthopaedic Surgery, University of California, Irvine, Irvine, California, USA
| | - Claire Thompson
- New York University Grossman School of Medicine, New York, New York, USA
| | - David P Trofa
- Department of Orthopedic Surgery, Columbia University Medical Center, New York, New York, USA
| | - Xinning Li
- Department of Orthopaedic Surgery, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Dean Wang
- Department of Orthopaedic Surgery, University of California, Irvine, Irvine, California, USA
| | - Robert L Parisien
- Department of Orthopaedic Surgery and Sports Medicine, Mount Sinai Health System, New York, New York, USA
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Ríos Luna A, Fahandezh-Saddi Díaz H, Villanueva Martínez M, Iglesias R, Prado R, Padilla S, Anitua E. Office-Based Intraosseous Infiltrations of PRGF as an Effective Treatment for Knee Osteoarthritis: A Retrospective Observational Clinical Study. J Clin Med 2023; 12:4512. [PMID: 37445547 DOI: 10.3390/jcm12134512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 06/28/2023] [Accepted: 07/04/2023] [Indexed: 07/15/2023] Open
Abstract
The aim of this study was to explore and assess office-based ultrasound-guided intraosseous and intra-articular infiltrations of plasma rich in growth factors (PRGF) in patients with moderate and severe knee osteoarthritis (KOA). Seventy-nine patients (30 women and 49 men) with grade 3-4 KOA according to the Kellgren-Lawrence classification participated in the study. All patients were treated with a minimally invasive technique using local anesthesia WALANT (wide-awake local anesthesia no tourniquet) in the ambulatory setting. A PRGF intra-articular infiltration and two intraosseous infiltrations in the tibial plateau and femoral condyle were performed weekly for a total of three sessions. The evaluation of the results was carried out using knee injury and osteoarthritis outcome score (KOOS) at baseline and post-treatment. After a follow-up period of 11 months (median) [interquartile range, 7-14], all the KOOS domains showed statistically significant improvement (p < 0.001). Moreover, 88% of the patients showed a pain reduction of at least 10 points (minimally clinically important improvement) from pre- to post-treatment. Our retrospective study using the in-office procedure of ultrasound-guided combination of intra-articular and intraosseous infiltrations of PRGF is a safe and efficacious approach for the treatment of grade 3-4 knee osteoarthritis.
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Affiliation(s)
- Antonio Ríos Luna
- Department of Traumatology and Orthopedic Surgery, Clínica Orthoindal, 04004 Almería, Spain
| | | | | | - Roberto Iglesias
- Department of Traumatology and Orthopedic Surgery, Clínica Orthoindal, 04004 Almería, Spain
| | - Roberto Prado
- Regenerative Medicine Laboratory, BTI-Biotechnology Institute I MAS D, 01007 Vitoria, Spain
| | - Sabino Padilla
- Regenerative Medicine Laboratory, BTI-Biotechnology Institute I MAS D, 01007 Vitoria, Spain
| | - Eduardo Anitua
- Regenerative Medicine Laboratory, BTI-Biotechnology Institute I MAS D, 01007 Vitoria, Spain
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20
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Belk JW, Lim JJ, Keeter C, McCulloch PC, Houck DA, McCarty EC, Frank RM, Kraeutler MJ. Patients With Knee Osteoarthritis Who Receive Platelet-Rich Plasma or Bone-Marrow Aspirate Concentrate Injections Have Better Outcomes Than Patients Who Receive Hyaluronic Acid: Systematic Review and Meta-analysis. Arthroscopy 2023:S0749-8063(23)00220-7. [PMID: 36913992 DOI: 10.1016/j.arthro.2023.03.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 02/13/2023] [Accepted: 03/01/2023] [Indexed: 03/15/2023]
Abstract
PURPOSE To systematically review the literature in order to compare the efficacy and safety of platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and hyaluronic acid (HA) injections for the treatment of knee osteoarthritis (OA). METHODS A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to identify Level I studies that compared the clinical efficacy of at least 2 of the following 3 injection therapies: PRP, BMAC, and HA for knee OA. The search phrase used was knee AND osteoarthritis AND randomized AND ("platelet rich plasma" OR "bone marrow aspirate" OR "hyaluronic acid"). Patients were primarily assessed based on patient-reported outcome scores (PROs) including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and Subjective International Knee Documentation Committee (IKDC) score. RESULTS Twenty-seven studies (all Level I) met inclusion criteria, including 1,042 patients undergoing intra-articular injection(s) with PRP (mean age 57.7 years, mean follow-up 13.5 months), 226 patients with BMAC (mean age 57.0 years, mean follow-up 17.5 months), and 1,128 patients with HA (mean age 59.0 years, mean follow-up 14.4 months). Non-network meta-analyses demonstrated significantly better post-injection WOMAC (p < 0.001), VAS (p < 0.01), and Subjective IKDC scores (p < 0.001) in PRP patients when compared to HA patients. Similarly, network meta-analyses demonstrated significantly better post-injection WOMAC (p < 0.001), VAS (p = 0.03), and Subjective IKDC (p < 0.001) scores in BMAC patients when compared to HA patients. There were no significant differences in post-injection outcome scores when comparing PRP to BMAC. CONCLUSION Patients undergoing treatment for knee OA with PRP or BMAC can be expected to experience improved clinical outcomes when compared to HA patients. LEVEL OF EVIDENCE I, Meta-Analysis of Level I studies.
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Affiliation(s)
- John W Belk
- University of Colorado School of Medicine, Aurora CO 80045
| | - Joseph J Lim
- University of Colorado Boulder, Boulder CO 80309
| | - Carson Keeter
- University of Colorado School of Medicine, Department of Orthopedics, Aurora CO 80045
| | - Patrick C McCulloch
- Houston Methodist Hospital, Department of Orthopedics & Sports Medicine, Houston TX 77030
| | - Darby A Houck
- University of Colorado School of Medicine, Aurora CO 80045
| | - Eric C McCarty
- University of Colorado School of Medicine, Department of Orthopedics, Aurora CO 80045
| | - Rachel M Frank
- University of Colorado School of Medicine, Department of Orthopedics, Aurora CO 80045
| | - Matthew J Kraeutler
- Houston Methodist Hospital, Department of Orthopedics & Sports Medicine, Houston TX 77030.
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Costa LAV, Lenza M, Irrgang JJ, Fu FH, Ferretti M. How Does Platelet-Rich Plasma Compare Clinically to Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review and Meta-analysis. Am J Sports Med 2023; 51:1074-1086. [PMID: 35316112 DOI: 10.1177/03635465211062243] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND There has been an increase in interest in the use of biological therapies in orthopaedic conditions such as knee osteoarthritis. Platelet-rich plasma (PRP) is one of these therapies, but it still lacks consistent results. PURPOSE To evaluate the effects (benefits and harms) of PRP intra-articular injection compared with other nonsurgical methods for the treatment of knee osteoarthritis. STUDY DESIGN Systematic review and meta-analysis of randomized and quasi-randomized controlled trials; Level of evidence, 2. METHODS Three electronic databases were searched to identify relevant studies published before January 2021. The primary outcomes were pain, function, and failure of treatment. Risks of bias of all trials were assessed using a Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation System was used to assess the quality of evidence of included studies. RESULTS A total of 40 studies with 3035 participants were included. Analysis of this review focused on comparing PRP with hyaluronic acid, corticosteroid, and saline, as we believe they are the most relevant comparisons with the most studies available. At 6-month follow-up, PRP was as effective as and in some studies more effective than other therapies regarding pain, function, and stiffness. However, current evidence is of low or very low quality and is based on trials with high risk of bias and great heterogeneity among them. No significant difference among treatments was found concerning major adverse events and treatment failure. CONCLUSION Although studies suggest that PRP may be more effective than or at least as effective as other modalities of nonsurgical treatment for knee osteoarthritis in terms of pain, function, and adverse events, serious limitations and methodological flaws are considerable in the current literature. Therefore, the authors are not able to make recommendations for clinical practice regarding PRP for knee osteoarthritis.
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Affiliation(s)
| | - Mário Lenza
- Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
| | - James J Irrgang
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Freddie H Fu
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Mário Ferretti
- Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
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Saraf A, Hussain A, Bishnoi S, Habib H, Garg A. Serial intraarticular injections of growth factor concentrate in knee osteoarthritis: A placebo controlled randomized study. J Orthop 2023; 37:46-52. [PMID: 36974096 PMCID: PMC10039117 DOI: 10.1016/j.jor.2023.02.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/01/2023] [Accepted: 02/13/2023] [Indexed: 03/29/2023] Open
Abstract
Objective To evaluate and compare clinical efficacy and effect on specific serum biomarker with serial injections of growth factor concentrate (GFC) for knee osteoarthritis (KOA) in a randomized triple blinded placebo controlled interventional study. Methods Final assessment was done on 58 patients. Patients with Kellgren-Lawrence grade II, III knee osteoarthritis were administered monthly intraarticular injections(3 injections) of GFC(n = 31) or saline(n = 27) and evaluated clinically with visual analogue scale(VAS) and Western Ontario and McMaster Universities Arthritis Index(WOMAC) at 3,6 and 12 months post therapy. Biochemical analysis was done with serum biomarker of cartilage degeneration, Collagen 2-1 (Coll2-1), estimated at baseline and at final follow up. Results Both the groups exhibited statistically significant improvements (P < 0.05) in VAS at 3,6 and 12 months. WOMAC improvement reached statistical significance for GFC group at every evaluation (P < 0.001) but only at 12 months in NS group (P = 0.029). The improvements were clinically meaningful only in GFC group throughout follow up (Minimal clinically important differences >12% of baseline in WOMAC and >2 cm difference in mean for VAS). Intergroup comparison revealed GFC to be much better for both scores at every evaluation (95% CI of 0.2-1.5,[P = 0.008], 1.4-2.9,[P < 0.0001], and 2.7-4.2,[P < 0.0001] for VAS, 7.3-16.0 [P < 0.001], 11.6-21.9 [P < 0.001] and 18.1-31.1[P < 0.001] for WOMAC). Statistically significant decrease in serum Coll2-1 levels were observed for GFC group only. No serious complications were seen. Conclusion Serial(three) monthly GFC injections result in clinically meaningful improvement of subjective pain and function outcome scores, sustaining up to 12 months in KOA grade II and III. GFC also lead to significant reduction in serum levels of cartilage degradation biomarker coll2-1.
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Affiliation(s)
- Amit Saraf
- Department of Orthopaedics, Teerthanker Mahaveer Medical College & Research Centre, Delhi Road. NH 24, Bagadpur, Moradabad, Uttar Pradesh, 244001, India
| | - Altaf Hussain
- Department of Orthopaedics, Teerthanker Mahaveer Medical College & Research Centre, Delhi Road. NH 24, Bagadpur, Moradabad, Uttar Pradesh, 244001, India
| | - Sandeep Bishnoi
- Department of Orthopaedics, Teerthanker Mahaveer Medical College & Research Centre, Delhi Road. NH 24, Bagadpur, Moradabad, Uttar Pradesh, 244001, India
| | - Hamza Habib
- Department of Orthopaedics, Teerthanker Mahaveer Medical College & Research Centre, Delhi Road. NH 24, Bagadpur, Moradabad, Uttar Pradesh, 244001, India
| | - Abhishek Garg
- Department of Orthopaedics, Teerthanker Mahaveer Medical College & Research Centre, Delhi Road. NH 24, Bagadpur, Moradabad, Uttar Pradesh, 244001, India
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The use of platelet-rich plasma in studies with early knee osteoarthritis versus advanced stages of the disease: a systematic review and meta-analysis of 31 randomized clinical trials. Arch Orthop Trauma Surg 2023; 143:1393-1408. [PMID: 35043252 DOI: 10.1007/s00402-021-04304-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Reports have concluded that platelet-rich plasma (PRP) is an effective and safe biological approach to treating knee osteoarthritis (OA). However, the effectiveness of PRP in advanced stages of the disease is not entirely clear. The purpose of this study was to evaluate whether the use of PRP would be as effective in studies with early-moderate knee OA patients compared to studies including patients with end-stage OA, based on the Kellgren-Lawrence classification. MATERIALS AND METHODS A comprehensive search in MEDLINE, EMBASE, Scopus, and Web of Science databases was conducted to identify randomized controlled trials (RCTs) comparing the effect of PRP injections versus other intra-articular treatments on pain and functionality. A meta-analysis was conducted using a random-effects model and the generic inverse variance method. RESULTS We included 31 clinical trials that reported data of 2705 subjects. Meta-analysis revealed an overall significant improvement of both pain [MD, - 1.05 (95% CI - 1.41 to - 0.68); I2 = 86%; P ≤ 0.00001] and function [SMD, - 1.00 (95% CI - 1.33, to - 0.66); I2 = 94%; P ≤ 0.00001], favoring PRP. Subanalysis for pain and functional improvement showed a significant pain relief in studies with 1-3 and 1-4 Kellgren-Lawrence OA stages and a significant functional improvement in studies with 1-2, 1-3 and 1-4 knee OA stages, favoring PRP. CONCLUSION Our results indicate that including patients with advanced knee OA does not seem to affect the outcomes of clinical trials in which the effectiveness of the PRP in knee OA is assessed.
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Saiz LC, Erviti J, Leache L, Gutiérrez-Valencia M. Restoring Study PRGF: a randomized clinical trial on plasma rich in growth factors for knee osteoarthritis. Trials 2023; 24:37. [PMID: 36653802 PMCID: PMC9850713 DOI: 10.1186/s13063-022-07049-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 12/23/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND A randomized clinical trial assessing plasma rich in growth factors (PRGF) versus hyaluronic acid for knee osteoarthritis was published in 2012 (sponsor trial ID BTI-01-EC/07/ART). Evidence of misreporting was discovered following access to unpublished materials. In accordance with the principles of the Restoring Invisible and Abandoned Trials (RIAT) initiative, we sought to re-analyse Study PRGF based on the unpublished trial materials. METHODS Reanalysis was made possible primarily based on two unpublished study documents (original trial protocol and final report) obtained from the authors of the original publication. A call to action, calling on the authors to correct the original publication, was publicly issued. The involved ethics committee was repeatedly approached and extensive discussion with the authors ensued. After no agreement to correct the paper was reached, we embarked on this restoration. Reanalysis was focused on providing updated analyses for efficacy and safety. RESULTS The efficacy of PRGF was not statistically different from hyaluronic acid for any prespecified primary or secondary efficacy outcomes. For the primary endpoint, the percent of patients on PRGF compared to hyaluronic acid with a decrease >40% in WOMAC pain subscale score was 5.4% higher; 95% confidence interval (CI) -10.4% to 21.3%; p = 0.505. This differs from the original publication that reported a non-prespecified primary endpoint (decrease >50% in WOMAC pain subscale score) which was 14.1% higher; 95% CI 0.5 to 27.6%; p=0.044. Furthermore, in contrast to the article statement that all the adverse events disappeared in 48 h, at least two patients in the hyaluronic arm and five patients in the PRGF arm reported persistent adverse events. Inadequate disclosure of conflicts of interest in the original publication was also noted. CONCLUSIONS This reanalysis of Study PRGF found no clinically or statistically significant benefit from PRGF compared to hyaluronic acid. The restoration of Study PRGF shows the urgency of important changes to trial reporting and oversight practices. In the future, timely access to all clinical trial documents is needed to minimize the risk of reporting bias. Similarly, ethics committees should be ready to intervene whenever a case of potential misconduct arises. TRIAL REGISTRATION This is a RIAT project, whose original trial was approved and registered on 19 December 2007 by the Ethics Committee of the Basque Country, Spain, as BTI-01-EC/07/ART.
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Affiliation(s)
- Luis Carlos Saiz
- Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain ,grid.508840.10000 0004 7662 6114IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Juan Erviti
- Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain ,grid.508840.10000 0004 7662 6114IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Leire Leache
- Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain ,grid.508840.10000 0004 7662 6114IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Marta Gutiérrez-Valencia
- Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain ,grid.508840.10000 0004 7662 6114IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
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Buchheit T. Platelet-Rich Plasma and Autologous Conditioned Serum: Non-Cellular Biologic Therapies for Neuroimmune Modulation and the Treatment of Arthritis Pain. NEUROIMMUNE INTERACTIONS IN PAIN 2023:287-303. [DOI: 10.1007/978-3-031-29231-6_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Chen L, Jin S, Yao Y, He S, He J. Comparison of clinical efficiency between intra-articular injection of platelet-rich plasma and hyaluronic acid for osteoarthritis: a meta-analysis of randomized controlled trials. Ther Adv Musculoskelet Dis 2023; 15:1759720X231157043. [PMID: 36950089 PMCID: PMC10026092 DOI: 10.1177/1759720x231157043] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 01/27/2023] [Indexed: 03/19/2023] Open
Abstract
Background Platelet-rich plasma (PRP) and hyaluronic acid (HA) are non-surgical treatments for osteoarthritis (OA), but the comparison of their efficiency is still inconclusive. Objectives The objectives of this study were to compare the efficacy of PRP and HA in the treatment of OA by meta-analysis and to explore the effects of different injection times and leukocyte concentration on the efficacy of PRP. Design Meta-analysis and subgroup analysis were conducted. The data were analyzed by Review Manager v5.4.1. Data sources and methods Articles were retrieved and screened from PubMed, the Cochrane Library, Web of Science, and Embase. The outcome included the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the visual analog scale (VAS), adverse events (AEs), the International Knee Documentation Committee (IKDC), and the satisfaction rate. Results A total of 30 articles involving 2733 patients were included. The total WOMAC score and IKDC score of the PRP group were better than those of the HA group at the last follow-up time, while there was no significant difference in AEs, satisfaction rate, and VAS between the two groups. In our subgroup analysis, there was no significant difference between single-injection PRP and triple-injection PRP. Leukocyte-poor PRP (LP-PRP) was better than leukocyte-rich PRP (LR-PRP) in IKDC, but there was no significant difference between them in the other scores. Conclusions In the treatment of OA, compared with HA, PRP performed better in the improvement of the patient's function. There was no significant difference in VAS and AEs between the two groups, and the safety was comparable. LP-PRP looked to be superior to LR-PRP in functional recovery, but there appeared to be no significant difference in pain relief between them. There was no significant difference between single PRP and triple PRP in the subgroup analysis.
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Affiliation(s)
- Lili Chen
- Department of Orthopaedic Surgery, Third
Xiangya Hospital of Central South University, Changsha, China
| | - Shirong Jin
- Department of Orthopaedic Surgery, Third
Xiangya Hospital of Central South University, Changsha, China
| | - Yunheng Yao
- Department of Orthopaedic Surgery, Third
Xiangya Hospital of Central South University, Changsha, China
| | - Sixian He
- Department of Orthopaedic Surgery, Third
Xiangya Hospital of Central South University, Changsha, China
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Kim JH, Park YB, Ha CW. Are leukocyte-poor or multiple injections of platelet-rich plasma more effective than hyaluronic acid for knee osteoarthritis? A systematic review and meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg 2022:10.1007/s00402-022-04637-5. [PMID: 36173473 DOI: 10.1007/s00402-022-04637-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 09/19/2022] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Platelet-rich plasma (PRP) has gained popularity as a treatment option for knee osteoarthritis; however, its efficacy remains controversial. The optimal leukocyte concentration and number of injections have not been well investigated. This study was, therefore, designed to provide clinical evidence on the leukocyte concentration and number of intra-articular injections of PRP via a meta-analysis of randomized controlled trials (RCTs). METHODS The MEDLINE, Embase, Cochrane Library, CINAHL, and Scopus databases were searched and RCTs comparing PRP and hyaluronic acid (HA) for treating knee osteoarthritis were included. Clinical outcomes, including visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and adverse reactions, were evaluated. RESULTS A total of 138 studies were screened, of which 21 level 1 RCTs (2086 knees; 1077 PRP and 1009 HA) were included. PRPs showed significant improvement in pain according to the VAS score compared to HA at 6 and 12 months, regardless of leukocyte concentration. Both single and multiple injections of PRP improved pain better than HA at 12 months. Regarding function, both single and multiple injections of leukocyte-poor PRP and leukocyte-rich PRP led to significantly better improvement in total WOMAC score compared with HA at 6 months. There was no significant difference in procedure-related knee pain or swelling between the PRP and HA groups. Leukocyte-rich PRP had a significantly higher odds ratio for procedure-related knee pain or swelling compared to HA (odds ratio, 3.3 [95% confidence interval, 1.1-10.2], P = .037). CONCLUSION Based on evidence from Level 1 studies, intra-articular injection of PRP improves pain and function in patients with knee osteoarthritis for up to 12 months and is superior to HA, regardless of leukocyte concentration or number of injections. The findings of this study support the routine clinical use of intra-articular injections of PRP for the treatment of knee osteoarthritis, regardless of the type and frequency of PRP injection. LEVEL OF EVIDENCE Meta-analysis of level I studies.
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Affiliation(s)
- Jun-Ho Kim
- Department of Orthopaedic Surgery, Center for Joint Diseases, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea
| | - Yong-Beom Park
- Department of Orthopedic Surgery, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, 110 Deokan-ro, Gwangmyeong-si, Gyeonggi-do, 14353, South Korea.
| | - Chul-Won Ha
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, South Korea
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Comparison between the effects of ultrasound guided intra-articular injections of platelet-rich plasma (PRP), high molecular weight hyaluronic acid, and their combination in hip osteoarthritis: a randomized clinical trial. BMC Musculoskelet Disord 2022; 23:856. [PMID: 36096771 PMCID: PMC9464606 DOI: 10.1186/s12891-022-05787-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 08/29/2022] [Indexed: 12/02/2022] Open
Abstract
Background Intra articular (IA) injection of platelet-rich plasma (PRP) and hyaluronic acid (HA) are of the new methods in the management of hip osteoarthritis (OA). The aim of this study was to compare the effectiveness of IA injections of PRP, HA and their combination in patients with hip OA. HA and PRP are two IA interventions that can be used in OA in the preoperative stages. Due to the different mechanisms of action, these two are proposed to have a synergistic effect by combining. Methods This is a randomized clinical trial with three parallel groups. In this study, patients with grade 2 and 3 hip OA were included, and were randomly divided into three injection groups: PRP, HA and PRP + HA. In either group, two injections with 2 weeks’ interval were performed into the hip joint under ultrasound guidance. Patients were assessed before the intervention, 2 months and 6 months after the second injection, using the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne questionnaires. Results One hundred five patients were enrolled randomly in HA, PRP and PRP + HA groups. All three groups showed significant improvement in WOMAC, VAS, and Lequesne at 2 months and 6 months compared with baseline. Comparison of the 3 groups demonstrated significant differences regarding WOMAC and Lequesne total scores and the activities of daily living (ADL) subscale of Lequesne (P = 0.041, 0.001 and 0.002, respectively), in which the observed improvement at 6th month was significantly higher in the PRP + HA and PRP groups compared to the HA group. Conclusion Although all 3 interventions were associated with improvement of pain and function in patients with hip OA, the therapeutic effects of PRP and PRP + HA injections lasted longer (6 months), and the effects of these two interventions on patients’ performance, disability, and ADL were superior to HA in the long run. Moreover, the addition of HA to PRP was not associated with a significant increase in the therapeutic results. Trial registration The study was registered at Iranian Registry of Clinical Trials (IRCT) website http://www.irct.ir/, a WHO Primary Register setup, with the registration number of IRCT20130523013442N30 on 29/11/2019.
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Ko PY, Li CY, Li CL, Kuo LC, Su WR, Jou IM, Wu PT. Single Injection of Cross-Linked Hyaluronate in Knee Osteoarthritis: A 52-Week Double-Blind Randomized Controlled Trial. Pharmaceutics 2022; 14:pharmaceutics14091783. [PMID: 36145530 PMCID: PMC9504468 DOI: 10.3390/pharmaceutics14091783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/13/2022] [Accepted: 08/22/2022] [Indexed: 11/16/2022] Open
Abstract
Background: to compare the 52-week effectiveness and safety between HYAJOINT Plus (HJP) and Durolane in knee osteoarthritis (OA) treatment. Methods: consecutive patients received a single injection of 3 mL HJP or Durolane. The primary outcome was a visual analog scale (VAS) pain measurement at 26 weeks post-injection. Secondary outcomes included other clinical, satisfaction, and safety assessments for 52 weeks. Results: 142 patients were equally randomized. At week 26, the HJP group had less VAS pain than the Durolane group (18.1 ± 9.5 versus 24.4 ± 14.0, p = 0.001). Both groups showed improvement in their VAS pain and stiffness scores, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and total scores for 52 weeks after injection (p < 0.001). However, the HJP group showed lower VAS pain and stiffness scores, reduced WOMAC pain and stiffness scores, a shorter Timed “Up & Go” (TUG) time, and a higher satisfaction score than the Durolane group for 39 weeks (p < 0.05). Only mild and self-limited adverse events occurred (40.8%). Conclusion: While a single injection of either HJP or Durolane is safe and effective for at least 52 weeks, HJP provided superior improvement in terms of VAS pain and stiffness scores, WOMAC pain and stiffness scores, and satisfaction score within 39 weeks of treatment.
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Affiliation(s)
- Po-Yen Ko
- Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, Taiwan
- Department of Biomedical Engineering, National Cheng Kung University, Tainan 701401, Taiwan
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan
- Department of Public Health, College of Public Health, China Medical University, Taichung 404328, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung 413305, Taiwan
| | - Chia-Lung Li
- Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, Taiwan
- Department of Orthopedics, Tainan Hospital, Ministry of Health and Welfare, Tainan 700043, Taiwan
| | - Li-Chieh Kuo
- Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan
- Medical Device Innovation Center, National Cheng Kung University, Tainan 701401, Taiwan
| | - Wei-Ren Su
- Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, Taiwan
- Medical Device Innovation Center, National Cheng Kung University, Tainan 701401, Taiwan
- Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan
| | - I-Ming Jou
- Department of Orthopedics, E-Da Hospital, Kaohsiung 824005, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 824005, Taiwan
- GEG Orthopedic Clinic, Tainan 701002, Taiwan
| | - Po-Ting Wu
- Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, Taiwan
- Department of Biomedical Engineering, National Cheng Kung University, Tainan 701401, Taiwan
- Medical Device Innovation Center, National Cheng Kung University, Tainan 701401, Taiwan
- Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan
- Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan
- Correspondence: ; Tel.: +886-6-276-6689
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Comparing the Efficacy of Intra-Articular Single Platelet-Rich Plasma(PRP) versus Novel Crosslinked Hyaluronic Acid for Early-Stage Knee Osteoarthritis: A Prospective, Double-Blind, Randomized Controlled Trial. Medicina (B Aires) 2022; 58:medicina58081028. [PMID: 36013495 PMCID: PMC9415551 DOI: 10.3390/medicina58081028] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 07/25/2022] [Accepted: 07/28/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Objectives: For the treatment of knee osteoarthritis (OA), intra-articular platelet-rich plasma (PRP) and novel crosslinked single-dose hyaluronic acid (HA) have both been reported to improve outcomes, but no study has compared them for the treatment of knee OA. We hypothesized patients with early-stage knee OA who received PRP injections would have more WOMAC score changes than those who received HA injections. This is the first prospective, double-blind, parallel, randomized controlled trial comparing the efficacy of intra-articular single-dose PRP versus novel crosslinked HA (HyajointPlus) for treating early-stage knee OA. Materials and Methods: This study analyzed 110 patients randomized into the PRP (n = 54) or HA (n = 56) groups. The primary outcome is the change of WOMAC score at 1-, 3-, and 6-month follow-ups compared to baseline. Results: The data revealed significant improvements in all WOMAC scores in the PRP group at 1-, 3-, and 6-month follow-up visits compared with the baseline level except for the WOMAC stiffness score at the 1-month follow up. In the HA group, significant improvements were observed only in the WOMAC pain score for all the follow-up visits and in WOMAC stiffness, function, and total scores at 6-month follow-up. When comparing the change of WOMAC score at 1-, 3-, and 6-month follow-ups, no significant differences were found between PRP and HA group. Conclusions: This study revealed that both PRP and HA can yield significant improvements in WOMAC scores at 6-month follow-up without any between-group differences at 1-, 3-, and 6-month follow-ups. Thus, both the single-injection regimens of PRP and HA can improve the functional outcomes for treating early-stage knee OA.
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The Clinical Efficacy of Platelet-Rich Plasma versus Conventional Drug Injection in the Treatment of Knee Osteoarthritis: A Study Protocol for a Randomized Controlled Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8767137. [PMID: 35656456 PMCID: PMC9153935 DOI: 10.1155/2022/8767137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 11/16/2021] [Accepted: 02/18/2022] [Indexed: 12/03/2022]
Abstract
Knee osteoarthritis is a common chronic degenerative joint disease in middle-aged and elderly people. Intra-articular injection for the treatment of knee osteoarthritis is a regularly utilized nonsurgical treatment in modern medicine. Hyaluronic acid (HA) and platelet-rich plasma (PRP) are two frequently employed intra-articular devices. Hyaluronic acid (HA) is an accepted nonsurgical treatment for symptomatic KOA, and platelet-rich plasma is a popular option in the treatment of KOA in recent years. The purpose of this research is to compare the efficacy and safety of intra-articular injection of platelet-rich plasma (PRP) versus hyaluronic acid (HA) on the pain score scale, knee function, and related inflammatory biomarkers in KOA patients using a clinical randomized controlled trial. Participants are being randomized into either the hyaluronic acid (HA) or into the platelet-rich plasma (PRP) group. All patients receive 4 weeks of treatment (once a week), and well-being support and quadriceps training (3 times a week). The primary outcomes are measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the visual analog scale (VAS). The secondary outcomes include the activities of daily living score, erythrocyte sedimentation rate, C-reactive protein testing, interleukin-6 levels, and X-ray examination. In order to monitor the occurrence of irregularities and abnormalities, patients are assessed at each visit, and restorative treatment is given if necessary. The results of this clinical trial will verify the efficacy of PRP and HA in the treatment of KOA and provide important evidence for the clinical treatment of KOA. The trial was enlisted at the Chinese Clinical Trial Registry on 26 September 2020 (ChiCTR2000038635).
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Cash C, Scott L, Walden RL, Kuhn A, Bowman E. Bibliometric analysis of the top 50 highly cited articles on platelet-rich plasma in osteoarthritis and tendinopathy. Regen Med 2022; 17:491-506. [PMID: 35578970 DOI: 10.2217/rme-2022-0024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
The primary goal of this study was to compile the top 50 most cited articles on the use of platelet-rich plasma (PRP). A search of relevant studies was performed in accordance with the PRISMA guidelines in Web of Science. The top 25 most cited articles in osteoarthritis and tendinopathy were then compiled and evaluated. Level 1 evidence articles constituted the majority of the studies (64%) and were more likely to have a higher citation density. Altmetric data was highest for level 1 systematic reviews. Of the articles that report a positive outcome for PRP, 13% (2/16) had low risk of bias. This study defines the most cited and influential publications regarding PRP to further research in this area.
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Affiliation(s)
- Carsen Cash
- Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Leon Scott
- Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Rachel Lane Walden
- Eskind Biomedical Library, Vanderbilt University, Nashville, TN 37232, USA
| | - Andrew Kuhn
- Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA
| | - Eric Bowman
- Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
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Ríos Luna A, Fahandezh-Saddi Díaz H, Villanueva Martinez M, Prado R, Padilla S, Anitua E. Office-Based Intraosseous Infiltrations of PRGF in Knee Osteoarthritis: Description of Technique. Arthrosc Tech 2022; 11:e917-e921. [PMID: 35646572 PMCID: PMC9134678 DOI: 10.1016/j.eats.2022.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/11/2022] [Indexed: 02/03/2023] Open
Abstract
Knee osteoarthritis is a low-degree inflammatory condition that involves the whole synovial joint tissues as an organ. Recently, a biological approach using plasma rich in growth factors (PRGF) to tackle not only the synovial joint with intraarticular injections of PRGF, but also the subchondral bone with intraosseous infiltrations has been implemented with promising results. However, this procedure requires sedation, which limits the implementation of the procedure to operating room. We propose a modified and less cumbersome PRGF intraosseous infiltration approach for moderate and severe knee osteoarthritis, conducting the procedure in the ambulatory setting assisted with WALANT (wide-awake local anesthesia no tourniquet) technique. The proposed technique with a minimally invasive local anesthesia involves subcutaneous infiltration of lidocaine and epinephrine in a solution without sedation, and using ultrasound guidance, thereby streamlining the original procedure. This procedure is both a cost-effective and safe approach that may contribute to the widespread use of intraosseous infiltrations.
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Affiliation(s)
- Antonio Ríos Luna
- Traumatología y Cirugía Ortopédica, Clínica Orthoindal, Almería, Spain,Address correspondence to Antonio Ríos Luna, M.D, M.D., Calle Rafael Alberti, 5, Department of Traumatología y Cirugía Ortopédica, Clínica Orthoindal, Almería 04004 - Spain.
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Tramś E, Malesa K, Pomianowski S, Kamiński R. Role of Platelets in Osteoarthritis-Updated Systematic Review and Meta-Analysis on the Role of Platelet-Rich Plasma in Osteoarthritis. Cells 2022; 11:1080. [PMID: 35406644 PMCID: PMC8997794 DOI: 10.3390/cells11071080] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 03/13/2022] [Accepted: 03/17/2022] [Indexed: 01/15/2023] Open
Abstract
Platelets are an essential component of hemostasis, with an increasing role in host inflammatory processes in injured tissues. The reaction between receptors and vascular endothelial cells results in the recruitment of platelets in the immune response pathway. The aim of the present review is to describe the role of platelets in osteoarthritis. Platelets induce secretion of biological substances, many of which are key players in the inflammatory response in osteoarthritis. Molecules involved in cartilage degeneration, or being markers of inflammation in osteoarthritis, are cytokines, such as tumor necrosis factor α (TNFα), interleukins (IL), type II collagen, aggrecan, and metalloproteinases. Surprisingly, platelets may also be used as a treatment modality for osteoarthritis. Multiple randomized controlled trials included in our systematic review and meta-analyses prove the effectiveness of platelet-rich plasma (PRP) as a minimally invasive method of pain alleviation in osteoarthritis treatment.
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Affiliation(s)
| | | | | | - Rafał Kamiński
- Centre of Postgraduate Medical Education, Department of Orthopaedics and Trauma Surgery, Professor A. Gruca Teaching Hospital, Konarskiego 13, 05-400 Otwock, Poland; (E.T.); (K.M.); (S.P.)
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Abbas A, Du JT, Dhotar HS. The Effect of Leukocyte Concentration on Platelet-Rich Plasma Injections for Knee Osteoarthritis: A Network Meta-Analysis. J Bone Joint Surg Am 2022; 104:559-570. [PMID: 34826301 DOI: 10.2106/jbjs.20.02258] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND It is hypothesized that leukocyte-poor (LP) platelet-rich plasma (PRP) is preferred over leukocyte-rich (LR) PRP for the treatment of knee osteoarthritis (OA). METHODS The MEDLINE, Embase, and Cochrane databases were reviewed for all English-language studies comparing LP-PRP or LR-PRP with relevant controls or each other. The follow-up periods were 6 months and 12 months. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between baseline and follow-up. The secondary outcome measures were changes in the WOMAC pain subscale, visual analog scale (VAS) for pain, and International Knee Documentation Committee (IKDC) subjective score between baseline and follow-up, and the incidence of local adverse reactions. Treatment outcomes were analyzed using the mean difference between treatments for continuous outcomes and the odds ratio for binary outcomes, with 95% credibility intervals. Treatment modalities were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Risk of bias was assessed using the relevant Cochrane tools, RoB 2 (version 2 of the Cochrane risk-of-bias tools) for randomized controlled trials (RCTs) and ROBINS-I (Risk of Bias in Non-Randomized Studies - of Interventions) for prospective comparative studies (PCSs). RESULTS This network meta-analysis included 23 studies: 20 RCTs and 3 PCSs, with a total of 2,260 patients and a mean follow-up period of 9.9 months. The overall risk-of-bias assessment of the RCTs revealed that 9 studies had low risk, 7 had some concerns, and 4 had high risk. The overall risk-of-bias assessment of the PCSs revealed that 1 study had low risk and 2 had moderate risk. We found no significant (p < 0.05) difference in all outcome measures and local adverse reactions between LP-PRP and LR-PRP. SUCRA rankings revealed that, for all outcome measures, LP-PRP is preferred to LR-PRP across follow-up periods. CONCLUSIONS Leukocyte concentration of PRP does not play a significant role in patient-reported outcome measures for knee OA. LP-PRP is preferred to LR-PRP according to SUCRA rankings, but this preference may not be important in clinical practice. LEVEL OF EVIDENCE Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Aazad Abbas
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Jin Tong Du
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Herman S Dhotar
- Department of Orthopaedic Surgery, North York General Hospital, University of Toronto, North York, Ontario, Canada
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
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A Multicenter, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled Phase I/IIa Study to Evaluate the Efficacy and Safety of a Single Intra-Articular Injection of YYD302 in Patients with Knee Osteoarthritis. J Clin Med 2022; 11:jcm11061482. [PMID: 35329808 PMCID: PMC8953367 DOI: 10.3390/jcm11061482] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/25/2022] [Accepted: 03/04/2022] [Indexed: 01/16/2023] Open
Abstract
This study was a phase I/IIa, multicenter, randomized, double-blinded, parallel, placebo-controlled clinical trial that aimed to assess the efficacy and safety of a single intra-articular injection of YYD302, a novel high-molecular-weight hyaluronic acid with divinyl sulfone cross-linking. Thirty adults with knee osteoarthritis were randomized to receive a single 2 mL intra-articular injection of YYD302 (test group 1), 3 mL of YYD302 (test group 2), or 3 mL of the placebo (placebo group). We compared the changes from the baseline in the weight-bearing pain of 100 mm using the Visual Analog Scale (VAS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Rheumatology-Osteoarthritis Research Society International (OMERACT-OASRSI) responder rates, and the use of rescue analgesics to assess the safety of this novel drug. A total of 26 subjects (10 in test group 1, 10 in test group 2, and 6 in the placebo group) were included in the full analysis set. At 12 weeks, only test groups 1 and 2 showed significant changes in the weight-bearing pain VAS scores (p = 0.0015 and p = 0.0085), symptoms, and average daily KOOS values compared to the baseline (p < 0.001, p = 0.0124, and p = 0.0018, p = 0.0426, respectively). While the rate and frequency of consuming the rescue drug continued to increase in the placebo group until 12 weeks, there was no change in the test groups. Our findings showed that YYD302, especially 2 mL of YYD302, reduced pain and improved knee joint function compared to the placebo.
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Lee CL, Wang YC, Huang HT, Chen CH, Chang KL, Tien YC. Efficacy of Intra-Articular Injection of Biofermentation-Derived High-Molecular Hyaluronic Acid in Knee Osteoarthritis: An Ultrasonographic Study. Cartilage 2022; 13:19476035221077404. [PMID: 35139660 PMCID: PMC9137304 DOI: 10.1177/19476035221077404] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVE The aim of this study is to evaluate the efficacy of intra-articular injection with HYAJOINT Plus, a biofermentation-derived, high-molecular hyaluronic acid (HA), on the progression of structural changes of cartilage in patients with knee osteoarthritis (OA) by using objectively promised ultrasonography (US) evaluation. DESIGN In this prospective clinical trial, 56 OA patients completed the study. One single dose of injection of HYAJOINT Plus into the knee cavity was performed. The primary efficacy outcome measure for structural change of knee joint was evaluated by US using a semiquantitative grading system. Secondary efficacy outcome measures included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total and subscale scores. All efficacy outcomes were measured at baseline and at first, third, and sixth month following treatment. RESULTS There were significant US grade-improvement changes of cartilage between baseline and follow-up visits over medial femoral condyle and transverse overall evaluation at 3- and 6-month follow-ups, and over lateral femoral condyle, intercondylar notch, and medial longitudinal area at 6-month follow-up. The improved score change of WOMAC from baseline was significant at 1- and 3-month follow-ups in pain subscale, whereas score change from baseline was significant at 6-month follow-up in total score and all 3 subscale scores. CONCLUSIONS It was determined that significant improvement was found on cartilage by US after intra-articular injection with high-molecular weight, biological fermentation-derived HYAJOINT Plus. The semiquantitative grading system by US is a promising tool to identify the efficacy on cartilage band after interventions.
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Affiliation(s)
- Chia-Ling Lee
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Physical Medicine and Rehabilitation, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ying-Chun Wang
- Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Orthopedics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsuan-Ti Huang
- Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Orthopedics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Hsin Chen
- Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan,Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kee-Lung Chang
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan,Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yin-Chun Tien
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan,College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan,Yin-Chun Tien, Professor, Department of Orthopedic Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung 807, Taiwan.
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Huda N, Islam MSU, Bishnoi S, Kumar H, Aggarwal S, Ganai AA. Role of Triple Injection Platelet-Rich Plasma for Osteoarthritis Knees: A 2 Years Follow-Up Study. Indian J Orthop 2022; 56:249-255. [PMID: 35140855 PMCID: PMC8789995 DOI: 10.1007/s43465-021-00459-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 07/11/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE To assess the clinical outcomes of intra-articular Platelet-rich plasma (PRP) injection in knee osteoarthritis (OA) at 2 year follow-up. METHODS This was a prospective interventional study. 68 cases (105 knees) with Kellgren-Lawrence (KL) grades I, II and III knee OA received 3 intra-articular injections of PRP 1 month apart. The cases were followed up for 2-years. Outcomes were measured using Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and Visual analog scale (VAS) scores. RESULTS The mean age was 51.7 years. 18 knees had KL grade I, 55 had grade II and 32 had grade III OA. The mean pre-treatment VAS score decreased significantly at 1 year (mean difference - 5.3, p = 0.003) and 2 year follow-up (mean difference - 6, p = 0.007). The mean pre-treatment WOMAC score decreased significantly at 1 year (mean difference - 45.9, p = 0.011) and at 2 year (mean difference - 52.4, p = 0.009). The WOMAC and VAS scores improved significantly from baseline to final follow-up across all KL grades (p = 0.001 and 0.001, 0.009 and 0.007, 0.021 and 0.017 for WOMAC and VAS across KL grade I, II and III, respectively). There was no significant differences in WOMAC and VAS scores between three KL grades at final follow-up (p = 0.17 and 0.09, respectively), although the baseline scores had significant difference (p = 0.001 for both VAS and WOMAC) with worse scores in higher KL grades. The variables like age, sex, BMI, KL grade, baseline VAS and baseline WOMAC did not predict the final VAS and WOMAC scores. CONCLUSION Triple injection of intra-articular PRP given one month apart significantly relieves the symptoms of knee OA till 2 years in KL grade I, II and III. The improvement in symptoms at 2-year follow-up did not differ across different KL grades.
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Affiliation(s)
- Najmul Huda
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Mir Shahid Ul Islam
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Sandeep Bishnoi
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Hemant Kumar
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Shubham Aggarwal
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
| | - Aijaz Ahmad Ganai
- Department of Orthopaedic Surgery, Teerthankar Mahaveer University, 4th floor, Moradabad, Uttar Pradesh 244001 India
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Zhang Q, Xu W, Wu K, Fu W, Yang H, Guo JJ. Intra-articular Pure Platelet-Rich Plasma Combined With Open-Wedge High Tibial Osteotomy Improves Clinical Outcomes and Minimal Joint Space Width Compared With High Tibial Osteotomy Alone in Knee Osteoarthritis: A Prospective Study. Arthroscopy 2022; 38:476-485. [PMID: 34571181 DOI: 10.1016/j.arthro.2021.09.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 09/04/2021] [Accepted: 09/07/2021] [Indexed: 02/05/2023]
Abstract
PURPOSE To compare the clinical efficacy of the patients with medial compartment knee osteoarthritis who underwent either opening-wedge high tibial osteotomy alone (HTO) or simultaneous HTO and pure platelet-rich plasma therapy (HTO+P-PRP). METHODS Eighty patients were divided into 2 groups randomly, the HTO-alone group (n = 41) and the HTO+P-PRP group (n = 39). Patients were matched for preoperative age, sex, and body mass index. The outcomes studied included visual analogue scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lysholm score. The minimum width of medial knee joint (MJSW), medial proximal tibial angle (MPTA), femoral tibial angle (FTA), and weightbearing line (WBL) were measured preoperatively, immediately postoperatively, and 1, 6, 12, and 24 months postoperatively. Paired t test and chi-squared test were used for statistical analysis. RESULTS All patients were followed up at 1, 6, 12, and 24 months postoperatively. At 1, 6, and 12 months, pain and function scores in the HTO+P-PRP group were better than those in the HTO-alone group, especially at 6 months in Lysholm score (HTO alone, 72.5 ± 10.6; HTO+P-PRP, 83.1 ± 14.7; P = .003, 95% CI -14.13 to -10.42) and WOMAC (HTO alone, 90.3 ± 11.9; HTO+P-PRP, 75.6 ± 15.4; P < .001, 95% CI 13.36 to 20.11). For both groups, no difference was found preoperatively (HTO alone, varus 3.5 ± 3.9; HTO+P-PRP, varus 4.1 ± 4.0; P = .898) or postoperatively (HTO alone, valgus 6.7 ± 4.5; HTO+P-PRP, valgus 7.7 ± 2.3; P = .768) in FTA or WBL. The increase of the MJSW in the HTO+P-PRP group was significantly greater than that in the HTO-alone group during the first year, especially at 6 months (HTO alone, 3.8 ± 1.2 mm; HTO+P-PRP, 4.6 ± 1.1 mm; P = .001, 95% CI -1.27 to -0.35). CONCLUSIONS Compared with HTO alone, HTO combined with intra-articular P-PRP improved the minimum medial knee joint space width during the first year postoperatively. Clinically, a higher proportion of patients in the HTO+P-PRP group exceeded the minimal clinically important difference (MCID) in the first year, especially at 6 months in Lysholm score (HTO alone, 65.9%; HTO+P-PRP, 97.4%) and WOMAC (HTO alone, 82.9%; HTO+P-PRP, 100.0%). LEVEL OF EVIDENCE 2, prospective comparative study.
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Affiliation(s)
- Qian Zhang
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China
| | - Wu Xu
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China
| | - Kailun Wu
- Department of Orthopedics, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, PR China
| | - Weili Fu
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, PR China
| | - Huilin Yang
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China
| | - Jiong Jiong Guo
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.
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Chan AG, Hoffmann JD, Pisquiy JJ, Belmont PJ, Dunn JC. Quality of prospective controlled randomized trials regarding platelet-rich plasma injection for osteoarthritis of the knee. J Orthop Sci 2022; 27:190-198. [PMID: 33441260 DOI: 10.1016/j.jos.2020.12.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 08/19/2020] [Accepted: 12/01/2020] [Indexed: 01/11/2023]
Abstract
BACKGROUND Randomized controlled trials (RCTs) are the gold standard for study design and are considered to have the highest level of evidence. The purpose of this study is to evaluate quality of evidence of prospective RCTs that investigated the clinical efficacy of platelet-rich plasma (PRP) treatments for knee osteoarthritis. We hypothesized that a high level of clinical evidence does not correlate with a high-quality scientific study. MATERIAL AND METHODS A systematic literature search to identified RCTs that evaluated the efficacy of PRP treatments for knee osteoarthritis. Inclusion criteria included studies that contained key terms "Platelet-rich plasma," "PRP", "knee", and "osteoarthritis". Exclusion criteria excluded studies that were not prospective RCTs. Ten RCTs were evaluated by four independent reviewers. The studies were assessed according to the Oxford Levels of Evidence, a modified Coleman Methodology Score, and the revised Consolidated Standards of Reporting Trials (CONSORT) score. RESULTS Three of the four Observers rated all 10 studies as Level I, while one Observer rated 80% of the studies as Level I. Using the Coleman Methodology Score, the average score for all studies was 58.0 out of 100 points, designating the studies as "fair." Areas of deficiency included clinical effect measurement and intent-to-treat analysis. Using the CONSORT checklist, the average score was 16.9 out of 22 points, designating the studies as "good". Areas of deficiency included inadequate implementation of randomization and interpretation of results. DISCUSSION Clinicians should critically evaluate research studies regardless of study design. A sophisticated study design and high level of evidence designation does not guarantee quality research. We determined that RCTs for PRP treatment of knee osteoarthritis were not as robust in quality despite their Level I Oxford Level of Evidence rating.
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Affiliation(s)
- Andrew G Chan
- Department of Orthopaedic Surgery, William Beaumont Army Medical Center, El Paso, TX, USA; Department of Orthopaedic Surgery, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA.
| | - Jeffrey D Hoffmann
- Department of Orthopaedic Surgery, William Beaumont Army Medical Center, El Paso, TX, USA.
| | - John J Pisquiy
- Department of Orthopaedic Surgery, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA.
| | - Philip J Belmont
- Department of Orthopaedic Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
| | - John C Dunn
- Department of Orthopaedic Surgery, William Beaumont Army Medical Center, El Paso, TX, USA.
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Van Schaik KD, Lee KS. Orthobiologics: Diagnosis and Treatment of Common Tendinopathies. Semin Musculoskelet Radiol 2021; 25:735-744. [PMID: 34937114 DOI: 10.1055/s-0041-1735475] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Orthobiologics, including platelet-rich plasma, prolotherapy, and mesenchymal stem cells, are seeing increasing use in the treatment of osteoarthritis (OA), muscle injury, and tendinopathy. This article reviews the biology and applications of orthobiologics in tendons, muscles, and joints, and focuses on platelet-rich plasma (PRP). Clinical evidence-based literature related to the use of PRP in the treatment of rotator cuff injury, lateral epicondylosis, Achilles tendinopathy, plantar fasciitis, knee OA, and acute muscle injury are discussed.
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Affiliation(s)
- Katherine D Van Schaik
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Kenneth S Lee
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.,Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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Filardo G, Previtali D, Napoli F, Candrian C, Zaffagnini S, Grassi A. PRP Injections for the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials. Cartilage 2021; 13:364S-375S. [PMID: 32551947 PMCID: PMC8808870 DOI: 10.1177/1947603520931170] [Citation(s) in RCA: 208] [Impact Index Per Article: 52.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE To evaluate effectiveness, in terms of patient-reported outcome measures, of platelet-rich plasma (PRP) injections for knee osteoarthritis compared to placebo and other intraarticular treatments. DESIGN PubMed, Cochrane Library, Scopus, Embase, Web of Science, as well as the gray literature were searched on January 17, 2020. Randomized controlled trials (RCTs) comparing PRP injections with placebo or other injectable treatments, in any language, on humans, were included. Risk of bias was assessed following the Cochrane guidelines; quality of evidence was graded using the GRADE guidelines. RESULTS Thirty-four RCTs, including 1403 knees in PRP groups and 1426 in control groups, were selected. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score favored PRP, with a statistically and clinically significant difference versus placebo at 12-month follow-up (P = 0.02) and versus HA (hyaluronic acid) at 6-month (P < 0.001) and 12-month (P < 0.001) follow-ups. A clinically significant difference favoring PRP versus steroids was documented for VAS (Visual Analogue Scale) pain (P < 0.001), KOOS (Knee Injury and Osteoarthritis Outcome Score) pain (P < 0.001), function in daily activities (P = 0.001), and quality of life (P < 0.001) at 6-month follow-up. However, superiority of PRP did not reach the minimal clinically important difference for all outcomes, and quality of evidence was low. CONCLUSIONS The effect of platelet concentrates goes beyond its mere placebo effect, and PRP injections provide better results than other injectable options. This benefit increases over time, being not significant at earlier follow-ups but becoming clinically significant after 6 to 12 months. However, although substantial, the improvement remains partial and supported by low level of evidence. This finding urges further research to confirm benefits and identify the best formulation and indications for PRP injections in knee OA.
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Affiliation(s)
- Giuseppe Filardo
- IRCCS Istituto Ortopedico Rizzoli,
Bologna, Italy,Ospedale Regionale di Lugano, Lugano,
Switzerland
| | - Davide Previtali
- Ospedale Regionale di Lugano, Lugano,
Switzerland,Davide Previtali, Orthopaedic and
Traumatology Unit, Ospedale Regionale di Lugano, EOC, Via Tesserete 46, Lugano
6900, Switzerland.
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Landro Carla Daffunchio Guillermo Cambiaggi Gustavo Galatro Horacio Caviglia ME, Daffunchio C, Cambiaggi G, Galatro GG, Caviglia H. Platelet-rich plasma vs platelet-rich plasma plus hyaluronic acid for haemophilic knee arthropathy treatment. Acta Orthop Belg 2021; 87:705-712. [PMID: 35172437 DOI: 10.52628/87.4.15] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Repeated joint bleeding leads to chronic synovitis, cartilage damage and bone alterations which result in haemophilic arthropathy and are associated with pain, functional impairment and poor quality of life. There are evidence that Hyaluronic Acid (HA) and Platelet-rich Plasma (PRP) have different mechanisms of action in the treatment of arthropathy for this reason we decided to use both components. The aim of this study is to compare, the efficacy, safety and duration of a single intra-articular injection of PRP against PRP+HA for pain, bleeding episodes and joint health, in the same patient with bilateral hemophilic knee arthropathy. Twenty-one men patients (42 knee joints) were treated with intra- articular injections of PRP or PRP+HA. All of them were haemophilia type A severe. The mean age was 36.6 years (21-72). All patients were evaluated for: Haemophilia Joint Health Score (HJHS), pain (VAS), the number of bleeding episodes (BE) in the last 30 days, before treatment, at three and six months after treatment. Statistically significant improvement were shown for both knee joints at three and six months after treatment for VAS and BE (P < 0.00001). The HJHS score did not significantly improve for either knee in the 6-month period after injection. A single PRP or PRP+HA injection is safe and effective in treating haemophilic arthropathy of the knee for up to 6 months follow-up, reducing pain, bleeding episodes and delaying total knee arthroplasty.
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Comparison of Minimally Invasive Procedures to Treat Knee Pain Secondary to Osteoarthritis: A Systematic Review and Meta-Analysis. J Vasc Interv Radiol 2021; 33:238-248.e4. [PMID: 34822993 DOI: 10.1016/j.jvir.2021.11.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 11/01/2021] [Accepted: 11/07/2021] [Indexed: 11/21/2022] Open
Abstract
PURPOSE To review and indirectly compare the outcomes of minimally invasive therapies for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS A literature search via Medline and Cochrane Central databases was completed for randomized control studies published between January 2000 to April 2020 for the following therapies: Rezum, Urolift, Aquablation, and prostate artery embolization (PAE). Data on the following variables were included: international Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), quality of life (QoL), and post-void residual (PVR). Standard mean differences between treatments were compared through a meta-analysis using transurethral resection of the prostate (TURP) to assess differences in treatment effect. RESULTS No significant difference in outcomes between therapies were noted for IPSS at the 3-, 6-, and 12-month follow-ups. Although outcomes for rezum were only available out to 3 months, there were no consistently significant differences in outcomes when comparing Aquablation vs PAE vs Rezum. TURP PVR was significantly better than Urolift at 3-, 6-, and 12 months. No significant differences in minor or major AEs were noted. CONCLUSION Although significant differences in outcomes were limited, aquablation and PAE were the most durable at 12 months. PAE has been well studied on multiple randomized control trials with minimal adverse events while aquablation has limited high quality data and has been associated with bleeding-related complications.
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Aw AAL, Leeu JJ, Tao X, Bin Abd Razak HR. Comparing the efficacy of dual Platelet-Rich Plasma (PRP) and Hyaluronic Acid (HA) therapy with PRP-alone therapy in the treatment of knee osteoarthritis: a systematic review and meta-analysis. J Exp Orthop 2021; 8:101. [PMID: 34735663 PMCID: PMC8569119 DOI: 10.1186/s40634-021-00415-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 10/13/2021] [Indexed: 12/16/2022] Open
Abstract
Purpose This study aims to compare the efficacy of a dual therapy of Platelet-Rich Plasma (PRP) and Hyaluronic Acid (HA) compared with PRP-alone therapy in the treatment of knee osteoarthritis (KOA). Methods PubMed, Embase, CINAHL, SCOPUS, Cochrane Library, grey literature and bibliographic references were searched from inception to January 2021. Only randomized controlled trials (RCTs) and retrospective cohort studies comparing the effect of PRP and HA versus PRP-alone therapy for KOA were included. Literature retrieval and data extraction were conducted by three independent reviewers. Pooled analysis of Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), International Knee Documentation Committee (IKDC) scores and adverse events were conducted. Results Ten studies (7 RCTs, 3 cohort studies) involving 983 patients were covered. Dual PRP and HA therapy resulted in significant reduction in VAS compared to PRP-alone therapy at 4–6 weeks (P < 0.00001) and 12 months (P < 0.00001). Dual therapy resulted in better WOMAC score improvement at 3 (P = 0.02), 6 (P = 0.05) and 12 months (P < 0.0001) compared to PRP-alone therapy. The IKDC score for dual therapy was also higher at 6 months compared to PRP-alone therapy (P = 0.007). Regarding adverse events, dual therapy was generally safer than PRP-alone therapy (P = 0.02). Conclusion While there is a paucity of large high-quality Level I studies, current best evidence suggests that dual therapy with PRP and HA for KOA may be effective at providing pain relief and improvement in function up to 1 year following administration. Level of evidence II.
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Affiliation(s)
- Angeline Ai Ling Aw
- Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Experimental Medicine Building, Singapore, 636921, Singapore
| | - Jun Jie Leeu
- Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Experimental Medicine Building, Singapore, 636921, Singapore
| | - Xinyu Tao
- Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Experimental Medicine Building, Singapore, 636921, Singapore
| | - Hamid Rahmatullah Bin Abd Razak
- Department of Orthopaedic Surgery, Sengkang General Hospital, 110 Sengkang East Way, Singapore, 544886, Singapore. .,SingHealth Duke-NUS Musculoskeletal Sciences Academic Clinical Programme, 20 College Road, Academia Level 4, Singapore, 169865, Singapore.
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Kikuchi N, Yoshioka T, Arai N, Sugaya H, Hyodo K, Taniguchi Y, Okuno K, Kanamori A, Yamazaki M. A Retrospective Analysis of Clinical Outcome and Predictive Factors for Responders with Knee Osteoarthritis to a Single Injection of Leukocyte-Poor Platelet-Rich Plasma. J Clin Med 2021; 10:jcm10215121. [PMID: 34768641 PMCID: PMC8584297 DOI: 10.3390/jcm10215121] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 12/21/2022] Open
Abstract
Although various platelet-rich plasma (PRP) kits are commercially available, the efficacy of these kits for knee osteoarthritis (KOA) has not been fully investigated. This study aimed to investigate the short-term results of leukocyte-poor PRP (LP-PRP) and the factors that contribute to its efficacy. We retrospectively reviewed 124 patients with KOA who were treated with LP-PRP. White blood cell (WBC) and platelet counts in the whole blood and the LP-PRP were measured. KOA severity was assessed using radiography. Clinical evaluation was performed both prior to injection and after an average of 3.3 weeks after the injection using the Japanese Knee Osteoarthritis Measure (JKOM). Responders were defined based on the JKOM. The contributing factors for responders were examined using a multivariate logistic analysis. The responder rate was 58.1% and the contributing factors for responders were a higher visual analog scale score before injection, WBC count in whole blood, and platelet concentration ratio of LP-PRP. The LP-PRP improved the clinical scores in the short term. Certain patient characteristics before injection and the concentration ratio of LP-PRP may be predictors of its efficacy; these may provide clues for elucidating which components of LP-PRP act on KOA pathologies.
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Affiliation(s)
- Naoya Kikuchi
- Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan; (N.K.); (N.A.); (K.H.); (K.O.); (A.K.); (M.Y.)
| | - Tomokazu Yoshioka
- Division of Regenerative Medicine for Musculoskeletal System, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan
- Correspondence:
| | - Norihito Arai
- Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan; (N.K.); (N.A.); (K.H.); (K.O.); (A.K.); (M.Y.)
| | - Hisashi Sugaya
- Department of Health, Faculty of Health Sciences, Tsukuba University of Technology, 4-3-15 Amakubo, Tsukuba 305-0005, Ibaraki, Japan;
| | - Kojiro Hyodo
- Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan; (N.K.); (N.A.); (K.H.); (K.O.); (A.K.); (M.Y.)
| | - Yu Taniguchi
- Department of Orthopaedic Surgery, Ichihara Hospital, 3681 Ozone, Tsukuba 300-3295, Ibaraki, Japan;
| | - Kosuke Okuno
- Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan; (N.K.); (N.A.); (K.H.); (K.O.); (A.K.); (M.Y.)
| | - Akihiro Kanamori
- Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan; (N.K.); (N.A.); (K.H.); (K.O.); (A.K.); (M.Y.)
| | - Masashi Yamazaki
- Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan; (N.K.); (N.A.); (K.H.); (K.O.); (A.K.); (M.Y.)
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Padilla S, Nurden AT, Prado R, Nurden P, Anitua E. Healing through the lens of immunothrombosis: Biology-inspired, evolution-tailored, and human-engineered biomimetic therapies. Biomaterials 2021; 279:121205. [PMID: 34710794 DOI: 10.1016/j.biomaterials.2021.121205] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 09/30/2021] [Accepted: 10/20/2021] [Indexed: 12/14/2022]
Abstract
Evolution, from invertebrates to mammals, has yielded and shaped immunoclotting as a defense and repair response against trauma and infection. This mosaic of immediate and local wound-sealing and pathogen-killing mechanisms results in survival, restoration of homeostasis, and tissue repair. In mammals, immunoclotting has been complemented with the neuroendocrine system, platelets, and contact system among other embellishments, adding layers of complexity through interconnecting blood-born proteolytic cascades, blood cells, and the neuroendocrine system. In doing so, immunothrombosis endows humans with survival advantages, but entails vulnerabilities in the current unprecedented and increasingly challenging environment. Immunothrombosis and tissue repair appear to go hand in hand with common mechanisms mediating both processes, a fact that is underlined by recent advances that are deciphering the mechanisms of the repair process and of the biochemical pathways that underpins coagulation, hemostasis and thrombosis. This review is intended to frame both the universal aspects of tissue repair and the therapeutic use of autologous fibrin matrix as a biology-as-a-drug approach in the context of the evolutionary changes in coagulation and hemostasis. In addition, we will try to shed some light on the molecular mechanisms underlying the use of the autologous fibrin matrix as a biology-inspired, evolution-tailored, and human-engineered biomimetic therapy.
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Affiliation(s)
- Sabino Padilla
- Eduardo Anitua Foundation for Biomedical Research, Vitoria, Spain; BTI-Biotechnology Institute ImasD, Vitoria, Spain; University Institute for Regenerative Medicine & Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain.
| | - Alan T Nurden
- Institut Hospitalo-Universitaire LIRYC, Hôpital Xavier Arnozan, Pessac, France
| | - Roberto Prado
- Eduardo Anitua Foundation for Biomedical Research, Vitoria, Spain; BTI-Biotechnology Institute ImasD, Vitoria, Spain; University Institute for Regenerative Medicine & Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain
| | - Paquita Nurden
- Institut Hospitalo-Universitaire LIRYC, Hôpital Xavier Arnozan, Pessac, France
| | - Eduardo Anitua
- Eduardo Anitua Foundation for Biomedical Research, Vitoria, Spain; BTI-Biotechnology Institute ImasD, Vitoria, Spain; University Institute for Regenerative Medicine & Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria, Spain.
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Wu CC, Tarng YW, Hsu DZ, Srinivasan P, Yeh YC, Lai YP, Hsieh DJ. Supercritical carbon dioxide decellularized porcine cartilage graft with PRP attenuated OA progression and regenerated articular cartilage in ACLT-induced OA rats. J Tissue Eng Regen Med 2021; 15:1118-1130. [PMID: 34581513 DOI: 10.1002/term.3252] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 07/09/2021] [Accepted: 09/04/2021] [Indexed: 11/06/2022]
Abstract
Knee osteoarthritis (OA) is a common degenerative articular disorder and considered one of the primary causes of pain and functional disability. Knee OA is prevalent in 10% of men and 13% of women aged 60 years above. The study aims to use cartilage tissue engineering that combines the triads of decellularized porcine cartilage graft as "scaffold," plasma rich platelet (PRP) as "signal" and chondrocytes from rat as "cell" to attenuate ACLT-induced OA progression and regenerate the knee cartilage in rats. Decellularization of the porcine cartilage was characterized by hematoxylin and eosin, 4,6-Diamidino-2-phenylindole staining, scanning electron microscopy and residual DNA quantification. The protective effect of decellularized porcine cartilage graft (dPCG) was evaluated by intra-articular administration in surgically induced anterior cruciate ligament transection (ACLT) rat osteoarthritis (OA) model. Supercritical carbon dioxide technology completely decellularized the porcine cartilage. Intra-articular administration of dPCG with or without PRP significantly reduced the ACLT-induced OA symptoms and attenuated the OA progression. Pain-relief by dPCG with or without PRP was assessed by capacitance meter and improved articular cartilage damage in the rat knee was characterized by X-ray and micro-CT. Besides, the histological analysis depicted cartilage protection by dPCG with or without PRP. The repairation and attenuation effect by dPCG with or without PRP in the articular knee cartilage damage were also explored by safranin-O, type II collagen, aggrecan and SOX-9 immuno-staining. To conclude, intra-articular administration of dPCG with or without PRP is efficient in repairing the damaged cartilage in the experimental OA model.
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Affiliation(s)
- Chia-Chun Wu
- Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Yih-Wen Tarng
- Department of Orthopedic, Kaohsiung Veterans General Hospital, Kaohsiung city, Taiwan, ROC
| | - Dur-Zong Hsu
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
| | | | - Yi-Chun Yeh
- R&D Center, ACRO Biomedical Co., Ltd., Kaohsiung City, Taiwan, ROC
| | - Yi-Ping Lai
- R&D Center, ACRO Biomedical Co., Ltd., Kaohsiung City, Taiwan, ROC
| | - Dar-Jen Hsieh
- R&D Center, ACRO Biomedical Co., Ltd., Kaohsiung City, Taiwan, ROC
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Use of Plasma Rich in Growth Factors and ReGeneraTing Agent Matrix for the Treatment of Corneal Diseases. Vision (Basel) 2021; 5:vision5030034. [PMID: 34287367 PMCID: PMC8293442 DOI: 10.3390/vision5030034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/21/2021] [Accepted: 06/28/2021] [Indexed: 11/21/2022] Open
Abstract
This study aimed to investigate the use of Plasma Rich in Growth Factors (PRGF) associated with tissue ReGeneraTing Agent (RGTA) drops for the treatment of noninfectious corneal ulcers. RGTA treatment was applied (one drop every two days); however, if ulcer closure was not achieved, PRGF eye drops treatment was added (four times/day). The time taken to reach the ulcer closure, the Best Corrected Visual Acuity (BCVA), intraocular pressure (IOP), Visual Analog Scale (VAS, in terms of frequency and severity of symptoms), and Ocular Surface Disease Index (OSDI) were evaluated. Seventy-four patients (79 eyes) were included, and the mean age was 56.8 ± 17.3 years. The neurotrophic corneal ulcer was the most frequent disorder (n = 27, 34.2%), mainly for herpes virus (n = 15, 19.0%). The time of PRGF eye drops treatment associated with the RGTA matrix was 4.2 ± 2.2 (1.5–9.0) months, and the follow-up period was 44.9 ± 31.5 months. The ulcer closure was achieved in 76 eyes (96.2%). BCVA, VAS and OSDI improved from the baseline (p < 0.001), and IOP remained unchanged (p = 0.665). RGTA and PRGF in noninfectious ulcers were effective and could be a therapeutic alternative for this type of corneal disease.
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Zhao D, Pan JK, Yang WY, Han YH, Zeng LF, Liang GH, Liu J. Intra-Articular Injections of Platelet-Rich Plasma, Adipose Mesenchymal Stem Cells, and Bone Marrow Mesenchymal Stem Cells Associated With Better Outcomes Than Hyaluronic Acid and Saline in Knee Osteoarthritis: A Systematic Review and Network Meta-analysis. Arthroscopy 2021; 37:2298-2314.e10. [PMID: 33713757 DOI: 10.1016/j.arthro.2021.02.045] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 02/26/2021] [Accepted: 02/26/2021] [Indexed: 02/02/2023]
Abstract
PURPOSE To perform a network meta-analysis to evaluate clinical efficacy and treatment-related adverse events (AEs) of intra-articular hyaluronic acid (HA), leukocyte-poor platelet-rich plasma (LP-PRP), leukocyte-rich platelet-rich plasma (LR-PRP), bone marrow mesenchymal stem cells (BM-MSCs), adipose mesenchymal stem cells (AD-MSCs), and saline (placebo) during 6 and 12 months of follow-up. METHODS Six databases were searched for randomized controlled trials. Outcome assessment included the visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscore, WOMAC score, International Knee Documentation Committee (IKDC) subjective score, and treatment-related AEs. Main inclusion criteria were at least one of the aforementioned outcome measurements, a minimum follow-up period of 5 months, and >80% patient follow-up. Treatments combined with the use of other operations or drugs were excluded. RESULTS Forty-three studies meeting the eligibility criteria were included. At 6 months, VAS scores and WOMAC pain subscores showed that AD-MSCs were the best treatment option (surface under the cumulative ranking curve [SUCRA] = 96.7%, SUCRA = 85.3%, respectively). According to WOMAC scores and subjective IKDC scores, LP-PRP was the most effective treatment (SUCRA = 86.0%, SUCRA = 80.5%, respectively). At 12 months, only AD-MSCs were associated with improved VAS scores compared with the placebo (weighted mean difference [WMD] = -20.93, 95% credibility interval [CrI], -41.71 to -0.78). Both LP-PRP and AD-MSCs were more beneficial than the placebo for improving WOMAC pain subscores (WMD = -30.08; 95% CrI, -53.59 to -6.25; WMD = -34.85; 95% CrI, -68.03 to -4.86, respectively). For WOMAC scores, LP-PRP and LR-PRP were significantly associated with improved WOMAC scores compared with the placebo after sensitivity analysis was performed (WMD = -35.26; 95% CrI, -64.99 to -6.01; WMD = -38.69; 95% CrI, -76.21 to -2.76). LP-PRP exhibited relatively better efficacy in improving subjective IKDC scores than the placebo (WMD = 13.67; 95% CrI, 4.05-23.39). Regarding safety, all treatments except for LP-PRP (relative risk = 1.83; 95% CrI, 0.89-4.64) increased treatment-related AEs compared with the placebo. CONCLUSIONS Based on the results of current research findings, during 6 months of follow-up, AD-MSCs relieved pain the best; LP-PRP was most effective for functional improvement. During the 12-month follow-up, both AD-MSCs and LP-PRP showed potential clinical pain relief effects; functional improvement was achieved with LP-PRP. Unfortunately, AD-MSC/LP-PRP functional comparisons were only based on WOMAC scores due to missing IKDC scores. BM-MSCs seem to have potentially beneficial effects, but the wide credibility interval makes it impossible to draw a well-supported conclusion. HA viscosupplementation clinical efficacy was lower than that of biological agents during follow-up, which may be related to the properties of the drugs. Considering the evaluation of treatment-related AEs, LP-PRP is the most advisable choice; although the AEs of these treatments are not serious, they may affect treatment compliance and satisfaction. LEVEL OF EVIDENCE Level II, meta-analysis of Level I and II studies.
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Affiliation(s)
- Di Zhao
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jian-Ke Pan
- Department of Orthopedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wei-Yi Yang
- Department of Orthopedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yan-Hong Han
- Department of Orthopedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ling-Feng Zeng
- Department of Orthopedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Bone and Joint Research Team of Degeneration and Injury, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Gui-Hong Liang
- Department of Orthopedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Bone and Joint Research Team of Degeneration and Injury, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Jun Liu
- Department of Orthopedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Bone and Joint Research Team of Degeneration and Injury, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China.
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