Single intra-articular injection with or without intra-osseous injections of platelet-rich plasma in the treatment of osteoarthritis knee: A single-blind, randomized clinical trial
BACKGROUND Subchondral bony structure damage plays an essential role in the pathogenesis of osteoarthritis (OA) knee. An intra-articular injection cannot reach the damaged subchondral bony structure and treat its pathologies effectively. The objective of the study was to compare the clinical effects of single intra-articular injection with or without intra-osseous injections of PRP in the treatment of osteoarthritis (OA) knee. METHODS This was a single-blind, parallel-group, randomized clinical trial. Fifty patients, with OA knee (K&L grade III), with ages between 50 and 65 years, were randomly allocated into 'intra-osseous, intra-articular PRP' ('IO+IA-PRP') (n = 25) or 'intra-articular PRP' group ('IA-PRP') (n = 25). Patients in the 'IO+IA-PRP' group received 18 ml PRP injection, and the 'IA-PRP' group received 8 ml PRP injection. Intra-osseous injections were given at the tibial plateau (5 ml) and femoral condyle (5 ml), along with intra-articular knee injection (8 ml), under fluoroscopic guidance. Outcomes were measured using VAS-pain, the knee injury and osteoarthritis outcome score (KOOS), and the treatment satisfaction scale. All patients (n = 50) were followed up till six months. RESULTS The mean age was 57.12(4.27) years and 57.00(4.96) years in the 'IO+IA-PRP' and 'IA-PRP' groups. Both groups showed significant improvement in pain relief (VAS pain) and KOOS parameters: pain, symptoms, ADL function, sport and recreation function, and quality of life. Compared to the 'IA-PRP' group, the 'IO+IA-PRP' group showed a greater reduction of VAS pain at six months. However, no significant difference was obtained in VAS pain-relief between these two groups (p = 0.422) at six months. Similarly, at 6 months, in inter-group comparison, except 'sport and recreation function' (p < 0.05), no significant differences were obtained in mean-scores of KOOS parameters: pain (p = 0.514); symptom (p = 0.148), ADL-function (p = 0.991), QoL-(p = 0.376). Patients in the 'IO+IA-PRP' group complained of significant 'injection-associated' adverse events and consumed a greater number of Acetaphenomen. CONCLUSIONS Both groups showed significant improvement following the intervention. Intra-osseous PRP injections did not provide any additional benefit over intra-articular PRP injection until six months regarding pain relief and functional improvement.
Platelet-rich plasma injection in the treatment of patellar tendinopathy: a systematic review and meta-analysis
Knee surgery & related research. 2022;34(1):22
PURPOSE The objective of the study was to assess the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of patellar tendinopathy. METHODS The PubMed, MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases were searched for clinical trials which compared PRP injection with other 'active treatment' interventions ('Non-PRP' injection and 'No-injection' treatments) or 'No-active treatment' interventions. Randomized and non-randomized clinical trials that had been published up to 15 November 2021, were included in the meta-analysis. The primary outcome, pain relief, was measured on a 'visual analog scale.' Secondary outcomes were knee functional activities and quality of life (QoL). The PRISMA guidelines were followed throughout the study. RESULTS Eight comparative studies were identified for inclusion in the meta-analysis. Assessment of these studies revealed that there were no significant differences in pain relief, functional outcomes, and QoL in the short, medium, and long term between PRP injection and Non-PRP injection interventions. Similarly, comparison of PRP injection to the No-active treatment intervention showed no differences in short- and medium-term pain relief. However, when PRP injection was compared to the No-injection treatment intervention extracorporeal shock wave therapy (ECWT), the former was found to be more effective in terms of pain relief in the medium term (mean difference [MD] - 1.50; 95% confidence interval [CI] - 2.72 to - 0.28) and long term (MD - 1.70; 95% CI, - 2.90 to - 0.50) and functional outcomes in the medium term (MD 13.0; 95% CI 3.01-22.99) and long term (MD 13.70; 95% CI 4.62-22.78). CONCLUSIONS In terms of pain relief and functional outcomes, the PRP injection did not provide significantly greater clinical benefit than Non-PRP injections in the treatment of patellar tendinopathy. However, in comparison with ESWT, there was a significant benefit in favor of PRP injection.
Safety and Efficacy of Platelet Rich Plasma for Treatment of Lumbar Discogenic Pain: A Prospective, Multicenter, Randomized, Double-blind Study
Pain physician. 2022;25(1):29-34
BACKGROUND Interventions for chronic discogenic spine pain are currently insufficient in lowering individual patient suffering and global disease burden. A 2016 study of platelet rich plasma (PRP) for chronic discogenic pain previously demonstrated clinically significant response among active group patients compared with controls. OBJECTIVES To replicate the previous research to move this intervention forward as a viable option for patient care. STUDY DESIGN A double-blind, randomized, placebo-controlled study. SETTING Multicenter private practices. METHODS Twenty-six (12 men, 14 women) human patients, ages 25 to 71 with a diagnosis of chronic lumbar discogenic pain, were randomly assigned to active (PRP) or control (saline) groups in a ratio of 2 active to 1 control. Baseline and follow-up Oswestry Disability Index and Numeric Pain Rating Scale questionnaires were obtained to track patient outcomes at 8 weeks postoperatively. RESULTS Within group assessment showed clinically significant improvement in 17% of PRP patients and clinically significant decline in 5% (1 patient) of the active group. Clinically significant improvement was seen in 13% of placebo group patients and no placebo patients had clinically significant decline secondary to the procedure. LIMITATIONS Possible explanations may include a range of factors including differences in patient demographics, outcome-measure sensitivity, or misalignment of statistical analyses. CONCLUSIONS These findings are markedly different than the highly promising results of the 2016 PRP study. This study posits necessary caution for researchers who wish to administer PRP for therapeutic benefit and may ultimately point to necessary redirection of interventional research for discogenic pain populations.
Efficacy of a Novel Intra-Articular Administration of Platelet-Rich Plasma One-Week Prior to Hyaluronic Acid versus Platelet-Rich Plasma Alone in Knee Osteoarthritis: A Prospective, Randomized, Double-Blind, Controlled Trial
Journal of clinical medicine. 2022;11(11)
Recent studies have suggested that the combined injection of platelet-rich plasma (PRP) and hyaluronic acid (HA) may have additive benefits for knee osteoarthritis over PRP alone, but there is insufficient evidence to support this combined injection. Moreover, the simultaneous injection of PRP and HA may offset the combined effect. Hence, the aim of this prospective, randomized, double-blind study was to assess their combined efficacy with a novel injection protocol. Forty-six study subjects with unilateral knee osteoarthritis were randomized to receive either a single-dose injection of HA (intervention group) or normal saline (control group) 1 week after a single-dose injection of leukocyte-poor PRP. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and static balance and the risk of falls measured by Biodex Balance System were, respectively, the primary and secondary outcome measures. Evaluations were performed at baseline, 1 month, 3 months, 6 months, and 12 months post-injection. The intervention group exhibited significant declines in WOMAC pain, stiffness, and total scores, as well as static balance, compared to the control group (p < 0.05). These randomized double-blind control trials, with novel protocol of intra-articular injection of PRP 1-week prior to HA, provide greater symptom relief and improve static balance compared to PRP alone in patients with knee osteoarthritis.
The Efficacy of Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis Symptoms and Structural Changes: A Systematic Review and Meta-Analysis
The Journal of arthroplasty. 2022
BACKGROUND Platelet-rich plasma (PRP) usage in orthopaedics continues to rise despite guidelines suggesting non-superiority to comparative cohorts. Therefore, we performed a systematic review and meta-analysis on PRP efficacy using two clinical assessments: (1) Visual Analog Scale (VAS) and (2) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We assessed consistency and clinical relevancy by determining study heterogeneity (e.g., sample sizes, ages, BMIs, arthritic severities, etc.). Comparative cohorts were: (A) hyaluronic acid (HA); (B) corticosteroid (CS); (C) normal saline (NS); and (D) exercise therapy. We performed sub-analyses of structural changes assessed on ultrasound, radiograph, or magnetic resonance imaging (MRI). METHODS We utilized PubMed, Cochrane Library, and Embase databases up to December 1, 2021, according to Preferred Reporting Items for Systematic-Reviews and Meta-Analyses guidelines. Twenty-four studies met criteria, with comparisons to: HA (n=11); CS (n=6); NS (n=5); and exercise therapy (n=3). Seven studies assessed structural changes. Evaluations utilized a methodological scoring system. I(2) statistics and forest plots pooled analyses and delineated study results. RESULTS PRP led to VAS and WOMAC improvements in most studies when compared to HA, CS, and NS (p≤0.05). Comparison to exercise therapy resulted in inconclusive findings (p≥0.05). However, substantial heterogeneity (I(2) ≥76%) was reported due to study variability. No differences were found when assessing structural changes or cartilage thickness by MRI (standardized mean difference -0.01 [-0.19, 0.18], p=0.91). CONCLUSIONS PRP may be associated with pain and functional improvements but was not clinically relevant (inconsistent study- and patient-metrics). Additionally, PRP did not confer superiority when assessing knee-related structural changes.
No Benefit to Platelet-rich Plasma Over Placebo Injections in Terms of Pain or Function in Patients with Hemophilic Knee Arthritis: A Randomized Trial
Clinical orthopaedics and related research. 2022
BACKGROUND Hemophilic knee arthritis is one of the most common presenting symptoms of hemophilia, and its management continues to be challenging to practitioners. Preliminary research has suggested that platelet-rich plasma (PRP) may have short-term efficacy in the treatment of hemophilic knee arthritis, but evidence for this treatment is limited. QUESTIONS/PURPOSES What is the effectiveness of PRP compared with placebo in (1) reducing pain and improving knee joint function (as measured by WOMAC, VAS, and Hemophilia Joint Health Score [HJHS]) and (2) improving quality of life (as measured by SF-36 scores) in patients with hemophilic knee arthritis through 24 months of follow-up? METHODS This was a prospective, parallel-group, double-blinded, single-center, placebo-controlled randomized clinical trial that included participants from a tertiary care center starting January 1, 2019, with follow-up completed on November 30, 2021. Participants were older than 18 years and had hemophilic knee arthritis confirmed by MRI, and they were randomly allocated to interventions in a 1:1 ratio. The investigators were not informed of the randomization sequence generated by the computer. Patient groups were comparable with respect to age, gender, BMI, hemophilia type, and disease severity at baseline. Physicians delivered three sessions (one per week) of a standard intraarticular injection of PRP (n = 95) or placebo (n = 95). The rate of successful blinding was balanced across the groups, which was assessed by asking participants which injection they thought they had received. The primary outcome was the WOMAC score (range 0 to 96; higher scores indicate more pain and worse function; minimum clinically important difference, 6.4 points) over 24 months. Among the 190 patients assigned to PRP or saline injections (mean age 31 ± 7 years), 100% (190) of patients were men). There was no between-group difference in the proportion of patients who completed the trial; 97% (92 of 95) of patients in the PRP group and 94% (89 of 95) of patients in the placebo group completed the trial. The most common adverse events were injection site discomfort 8% (8 of 95) in the PRP group and 4% (4 of 95) in the placebo group. An intention-to-treat analysis was planned, but there was no crossover between groups. All patients were included in the analyses. With 95 patients in each group, the study was powered a priori at 90% to detect a difference in WOMAC score of 6.4 points, which was considered a clinically important difference. RESULTS There were no clinically important differences in the mean WOMAC, VAS pain, HJHS, SF-36, and MRI scores between groups at any timepoint. Intraarticular PRP did not ameliorate function, symptoms, and quality of life in patients with hemophilic knee arthritis. At 24 months of follow-up, the mean difference between the PRP and placebo groups in the WOMAC score was -1 (95% CI -5 to 2; p = 0.42). The mean difference in the VAS pain score was -0.3 (95% CI -0.8 to 0.2; p = 0.19), in the HJHS was -0.6 (95% CI -1.4 to 0.1; p = 0.10), in the SF-36 physical component summary was 0 (95% CI -2 to 3; p = 0.87), and in the SF-36 mental component summary was -1 (95% CI -3 to 2; p = 0.64). The mean differences in the MRI scores of soft tissue and osteochondral subscore were 0.1 (95% CI -0.3 to 0.5; p = 0.59) and -0.3 (95% CI -0.7 to 0.1; p = 0.19), respectively. CONCLUSION Among patients with hemophilic knee arthritis, three intraarticular PRP injections, compared with placebo injections, did not improve hemophilic knee symptoms, function, and quality of life over 24 months. The results of this study do not support the use of PRP injections in patients who have hemophilic knee arthritis. LEVEL OF EVIDENCE Level I, therapeutic study.
Allogeneic platelet-derived growth factors local injection in treatment of tennis elbow: a prospective randomized controlled study
International orthopaedics. 2022
PURPOSE The purpose of this study aimed to evaluate the efficacy of local injection of allogeneic platelet-derived growth factors in treatment of patients with tennis elbow. PATIENTS AND METHODS This study included 120 tennis elbow patients randomly divided into two groups. The patients were locally injected with allogeneic growth factors (treatment group) or with normal saline (control group). The outcomes were assessed using Patient-Related Tennis Elbow Evaluation (PRTEE) and quick Disabilities of the Arm, Shoulder and Hand (qDASH) scales. The clinical outcomes were accordingly classified as excellent, good and poor. The patient's satisfaction and adverse effects were also recorded. RESULTS There was no statistically significant difference between the two groups regarding the age, gender, dominant arm or the pre-injection scores. At three month follow-up, the reductions in the mean PRTEE and qDASH scores were 88.7% and 70.6% in the treatment group versus 21.8% and 14.9% in the control group, respectively. At the last follow-up, the outcomes in the treatment group were excellent in 85% of patients and good in 15%, versus 8% and 32% in the control group. Overall, 95% were satisfied in the treatment group compared to 25% in control group. Forty patients in the treatment group experienced mild transient post-injection pain. CONCLUSION This study strongly suggests that local injection of allogeneic platelet-derived growth factors could be a promising safe treatment option for tennis elbow with significant pain relief, functional improvement and patient's satisfaction. Yet, additional larger studies are needed to assess the durability of these outcomes.
How Does Platelet-Rich Plasma Compare Clinically to Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review and Meta-analysis
The American journal of sports medicine. 2022;:3635465211062243
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.
Platelet-Rich Plasma Injection in Non-Operative Treatment of Partial-Thickness Rotator Cuff Tears: A Systematic Review and Meta-Analysis
Journal of rehabilitation medicine. 2022;:jrm00312
OBJECTIVE Partial-thickness rotator cuff tears have a high prevalence in older people. Treatment for such tears remains controversial. Platelet-rich plasma has recently attracted attention for treating partial-thickness rotator cuff tears, due to its regenerative characteristics. However, the results of application of platelet-rich plasma in non-operative treatments are unclear. The aim of this review is to evaluate the effects on shoulder function improvement and pain relief of platelet-rich plasma injection in partial-thickness rotator cuff tears, at different follow-up times (3-6 weeks, 8-12 weeks, and more than 24 weeks after treatment) compared with placebo or corticosteroids. DESIGN A systematic review and meta-analysis. METHODS Several databases, including PubMed, EMBASE, and Cochrane, were searched. Eleven studies met the inclusion criteria for the meta-analysis. The quality of research was evaluated using the Cochrane risk-of-bias tool. The effectiveness of platelet-rich plasma was calculated as the difference between baseline measurements and post-injection outcomes. The standardized mean difference was used to compare different outcome scales or questionnaire measurements. Statistical analysis was performed using Stata 15.0. RESULTS The analysis included 11 studies, with a total of 641 patients (318 treated with platelet-rich plasma and 323 controls). Compared with placebo, platelet-rich plasma exhibited significantly better effects on shoulder function improvement and pain relief at all 3 follow-up times. Compared with other conservative treatments, platelet-rich plasma exhibited significantly better effects on shoulder function and pain relief at 8-12 weeks and at more than 24 weeks after treatment. CONCLUSION This review showed positive effects on shoulder function improvement and pain relief of the use of platelet-rich plasma in treating partial-thickness rotator cuff tears, especially in relatively late stages of follow-up (more than 8 weeks) after treatment.
Efficacy of Ultrasound-Guided Glenohumeral Joint Injections of Leukocyte-Poor Platelet-Rich Plasma Versus Hyaluronic Acid in the Treatment of Glenohumeral Osteoarthritis: A Randomized, Double-Blind Controlled Trial
Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine. 2022
OBJECTIVE To compare the efficacy of ultrasound-guided hyaluronic acid (HA) versus leukocyte-poor platelet-rich plasma (LP-PRP) injection in the treatment of glenohumeral osteoarthritis. DESIGN Double-blind randomized controlled trial. SETTING Academic institution. PATIENTS Seventy patients with chronic glenohumeral osteoarthritis were randomly assigned to receive a single injection of HA (n = 36) or LP-PRP (n = 34). INTERVENTIONS Leukocyte-poor platelet-rich plasma was processed using Harvest/TerumoBCT Clear PRP kits. Ultrasound-guided injections of 6 mL HA or 6 mL LP-PRP into the glenohumeral joint were performed. Patients, the injecting physician, and outcomes assessor were blinded to treatment assignments. MAIN OUTCOME MEASURES Shoulder Pain and Disability Index (SPADI), American Shoulder and Elbow Surgeons (ASES) score, current/average numerical rating scale (NRS) pain scores, satisfaction, and side effects were assessed at the 5 follow-up time points over 12 months. RESULTS Baseline characteristics were similar between groups. There were no significant between-group differences regarding SPADI, ASES, and current/average NRS pain scores at any time point up to 12 months postinjection (P > 0.05). However, significant improvements in SPADI, ASES, and current/average NRS pain scores were observed in both groups starting at 1 or 2 months (P < 0.01, P < 0.01, P < 0.001, and P < 0.01, respectively). These improvements were observed regardless of osteoarthritis severity. For patients who received LP-PRP, there was no effect of platelet yield on outcomes. Side effect and satisfaction rates were similar between groups. CONCLUSIONS There were no differences in pain and functional outcomes after a single injection of LP-PRP versus HA. However, significant improvements in pain and function were observed after both treatments in patients with glenohumeral osteoarthritis.