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.
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.
Intra-Articular Leukocyte-Rich Platelet-Rich Plasma versus Intra-Articular Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Meta-Analysis of 14 Randomized Controlled Trials
Pharmaceuticals (Basel, Switzerland). 2022;15(8)
(1) Background: To evaluate the clinical effects of leukocyte-rich platelet-rich plasma (LR-PRP) and hyaluronic acid (HA) injections in treating patients suffering from knee osteoarthritis (OA); (2) Methods: Randomized controlled trials (RCTs) were searched from PubMed, Web of Science, and Cochrane Library. Keywords were: platelet-rich plasma, LR-PRP, leukocyte-rich, hyaluronic acid, and knee osteoarthritis. The included RCTs were published between the 1st of November 2011 and the 3rd of February 2021. Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, visual analog scale (VAS) scores, International Knee Documentation Committee (IKDC) scores, and adverse events were used as outcomes for evaluation; (3) Results: A total of 14 RCTs were enrolled. At 6 months, revealed that the LR-PRP group was better than the HA group in WOMAC total, pain, and physical function scores. At 12 months, the LR-PRP group was better than the HA group in WOMAC stiffness and physical function scores. There was no significant difference in adverse events; (4) Conclusion: LR-PRP injection showed no significant pain relief effect as compared with HA injection. However, LR-PRP demonstrated better overall outcomes as compared to HA in knee OA patients at the follow-up periods of 3, 6, and 12 months. LR-PRP injection may be recommended as a feasible option in treating patients with knee OA.
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
Archives of orthopaedic and trauma surgery. 2022
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); I(2) = 86%; P ≤ 0.00001] and function [SMD, - 1.00 (95% CI - 1.33, to - 0.66); I(2) = 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.
The Use of Intra-articular Platelet-Rich Plasma as a Therapeutic Intervention for Hip Osteoarthritis: A Systematic Review and Meta-analysis
The American journal of sports medicine. 2022;:3635465221095563
BACKGROUND There is a cohort of patients in whom hip preservation surgery is not indicated, because they have developed signs of early osteoarthritis (OA), and nor can they have a hip replacement, as they are too early in the disease process. Management of this cohort of patients is not standardised and both pharmacological and nonpharmacological measures are utilised to reduce pain. Interventions available for early OA include intra-articular injections of steroids, viscosupplementation and more recently platelet-rich plasma (PRP). However, the use of PRP in hip OA has not yet been studied systematically. PURPOSE To assess intra-articular PRP as a therapeutic intervention for hip OA, including the duration of efficacy, influence of dose and composition of PRP, and the incidence of adverse effects. STUDY DESIGN A systematic review and meta-analysis; Level of evidence, 4. METHODS We performed literature searches on the MEDLINE, EMBASE, CINAHL, WEB OF SCIENCE, COCHRANE, and SCOPUS databases, and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Data were pooled using random-effects meta-analysis. We assessed the quality of the included studies using the methodological index for non-randomized studies instrument, with an additional assessment for randomized controlled trials with the revised Cochrane risk of bias tool for randomized trials. This is the first study to concisely collate the available data on the use of PRP in hip OA. RESULTS Eight studies were included in the analysis, with data from a total of 331 patients. PRP significantly reduced pain compared with the baseline at multiple time points, with the greatest effect at the 1- to 2-month follow-up, but PRP significantly improved function only at the 1- to 2-month follow-up. A significantly larger reduction in pain was achieved with a single injection of PRP compared with multiple injections, a total injected dose of PRP <15 mL compared with ≥15 mL, and use of a leukocyte-poor PRP preparation compared with leukocyte-rich PRP. There were no lasting adverse effects. CONCLUSION Low- and moderate-quality evidence suggests that PRP reduces pain and improves function at the end-point follow-up of studies compared with the baseline. Moderate-quality evidence suggests that a larger reduction in pain is achieved with a single injection of PRP compared with multiple injections, and low-quality evidence attributes a larger reduction of pain with a total injected dose of PRP <15 mL compared with ≥15 mL and using leukocyte-poor PRP compared with leukocyte-rich PRP.
Platelet-Rich Plasma Therapy Ensures Pain Reduction in the Management of Lateral Epicondylitis - A PRISMA-compliant Network Meta-Analysis of Randomised Controlled Trials
Expert opinion on biological therapy. 2022
OBJECTIVES We aim to analyze the effectiveness of platelet-rich plasma (PRP) therapy in comparison to all the available treatments in the management of lateral epicondylitis. MATERIALS AND METHODS We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library till June 2021 for randomized controlled trials (RCTs), analyzing the efficacy and safety of PRP in the management of lateral epicondylitis. Visual Analog Score (VAS) for pain, Disabilities of the Arm, Shoulder and Hand (DASH) Score, Patient Reported Tennis-Elbow Evaluation (PRETEE) Score were the outcomes analyzed. Analysis was performed in R-platform using MetaInsight. Available treatment methods in the network were ranking based on the p-score approach. The quality of results from network analysis was appraised with Cochrane's CINeMA approach. RESULTS 25 RCTs with 2040 patients were included in the network analysis. Compared to saline control, only leucocyte-rich PRP resulted in significant pain relief (WMD -14.8 95% CI [-23.18,-6.39]; low confidence) on network analysis of VAS outcome compared to other treatment methods such as steroid, local anesthetic, laser, and surgery. Concerning functional outcome parameters such as DASH score or PRETEE score, none of the above-mentioned treatment methods were superior to saline control. On subgroup analysis of the outcomes at various time points, LR-PRP resulted in clinically significant improvement at all time points analyzed. Upon ranking the probabilities of being best of all the interventions analyzed in the network, leucocyte-rich PRP seems more promising with a p score of 0.415. CONCLUSION PRP therapy offers significant pain relief compared to saline control when employed in the management lateral epicondylitis. However, we did not note similar improvement in functional outcomes measures. With the available low-quality evidence, PRP is ranked to be the most promising therapy that needs further exploration. Further high-quality RCTs are needed to explore its usefulness in lateral epicondylitis.
The Statistical Fragility of Platelet-Rich Plasma as Treatment for Chronic Noninsertional Achilles Tendinopathy: A Systematic Review and Meta-analysis
Foot & ankle orthopaedics. 2022;7(3):24730114221119758
BACKGROUND Randomized controlled trial (RCT) outcomes reaching statistical significance, frequently determined by P <.05, are often used to guide decision making. Noted lack of reproducibility of some RCTs has brought special attention to the limitations of this approach. In this meta-analysis, we assessed the robustness of RCTs evaluating platelet-rich plasma (PRP) for the treatment of chronic noninsertional Achilles tendinopathy (AT) by using fragility indices. METHODS The present study was a systematic review and meta-analysis of RCTs comparing outcomes after PRP injection vs alternative treatment in patients with AT. Representative data sets were generated for each reported continuous outcome event using summary statistics. Fragility indices refer to the minimal number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result into a nonsignificant result, or vice versa. The fragility index (FI) and continuous FI (CFI) were determined for dichotomous and continuous outcomes, respectively, by manipulating each data set until reversal of significance (a=0.05) was achieved. The corresponding fragility quotient (FQ) and continuous FQ (CFQ) were calculated by dividing FI/CFI by sample size. RESULTS Of 432 studies screened, 8 studies (52 outcome events) were included in this analysis. The 12 dichotomous outcomes had a median FI of 4.5 (FQ: 0.111), and the 40 continuous outcomes had a median CFI of 5 (CFQ: 0.154). All 52 outcome events included lost-to-follow-up data, and 12 (23.1%) indicated a greater number of patients lost to follow-up than the FI or CFI. CONCLUSION Our findings suggest that RCTs evaluating PRP for AT therapy lack statistical robustness, because changing only a small number of events may alter outcome significance. LEVEL OF EVIDENCE Level II, therapeutic study.
The effect of autologous fat grafting and platelet-rich plasma injections in osteoarthritis of the CMC joint of the thumb: a systematic review and meta-analysis
Plastic and reconstructive surgery. 2022
BACKGROUND For the treatment of CMC arthritis of the thumb various therapies are used. Infiltration therapy with autologous substances such as platelet-rich plasma and autologous fat have recently gained increasing attention due to beneficial pain-reducing effects in arthritis and the associated regenerative potential.The extent of clinical evidence in this area, however, and how well autologous substances work in terms of pain reduction and improvements in hand function remains unclear. METHODS A systematic review and meta-analysis were conducted to evaluate the current evidence and to provide more insight into pain reduction and improvement in hand function after infiltration of autologous substances. We identified 11 clinical trials of which we included 8 in the meta-analysis. RESULTS Autologous substances achieved a good and long-lasting pain reduction, which may also be accompanied by corresponding improvement in hand function. Autologous substances appear to be more effective than corticoid infiltrations. The infiltration of autologous fat seems to be particularly promising in more advanced stages of CMC arthritis of the thumb also.Our meta-analysis showed a mean pain reduction of 2.4-3 in VAS score and a reduction of 18-19 points in the DASH questionnaire after infiltration with autologous substances. CONCLUSIONS In conclusion, both PRP and autologous fat infiltration offer an efficient and long lasting minimally invasive therapy option in the treatment of CMC arthritis of the thumb.
Failure to disclose industry funding impacts outcomes in randomized controlled trials of platelet-rich plasma
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2022
PURPOSE Platelet-rich plasma (PRP) represents a highly profitable biological therapy. Platelet-rich plasma is widely used to treat musculoskeletal disorders despite mixed evidence of its efficacy. As evidenced by literature from other domains, industry funding may influence the results of clinical trials. The objective of the current study was to determine the association between industry funding and positive results for randomized controlled trials (RCTs) assessing the efficacy of PRP in musculoskeletal disorders. METHODS A search of four databases was conducted. Included studies were RCTs comparing PRP to any non-PRP comparator in adults (18 years old or over) with musculoskeletal disorders and had full text available in English. Studies were excluded if they were published before 2016 or were non-human trials. A multivariate binomial logistic regression model was created to explore predictors of statistically significant findings. Covariates included the presence of industry funding, sample size, and length of study follow-up. 1440 records were screened with 87 trials included in the final analysis. RESULTS Of the 87 studies, 61 (70%) reported a statistically significant primary outcome. The presence of industry funding was not predictive of a statistically significant primary outcome [OR = 0.36, 95% CI 0.096-1.36, (n.s.)]. Studies that did not state whether industry funding was present had a higher chance of reporting a statistically significant primary outcome (OR = 3.61, 95% CI 1.1-11.9, p = 0.035). Sample size and length of follow-up were not predictive of a statistically significant primary outcome. CONCLUSION The results of the current study conclude that industry funding had no impact on the reporting of positive results for RCTs investigating PRP in musculoskeletal disorders. However, not disclosing sources of funding was associated with a higher likelihood of reporting positive results. The results of trials that fail to disclose funding sources should be interpreted with caution in the PRP literature. LEVEL OF EVIDENCE I.
Platelet-Rich Plasma in acute Achilles tendon ruptures: A systematic review and meta-analysis
Foot (Edinburgh, Scotland). 2022;53:101923
BACKGROUND Platelet Rich Plasma (PRP) is known to exert multi-directional biological effects favouring tendon healing. However, conclusions drawn by numerous studies on its clinical efficacy for acute Achilles tendon rupture are limited. We performed a systematic review and meta-analysis to investigate this and to compare to those without PRP treatment. METHODS The Cochrane Controlled Register of Trials, Pubmed, Medline and Embase were used and assessed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria with the following search terms: ('plasma' OR 'platelet-rich' OR 'platelet-rich plasma' or 'PRP') AND ('Achilles tendon rupture/tear' OR 'calcaneal tendon rupture/tear' OR 'tendo calcaneus rupture/tear'). Data pertaining to biomechanical outcomes (heel endurance test, isokinetic strength, calf-circumference and range of motion), patient-reported outcome measures (PROMs) and incidence of re-ruptures were extracted. Meta-analysis was performed for same outcomes measured in at least three studies. Pooled outcome data were analysed by random- and fixed-effects models. RESULTS After abstract and full-text screening, 6 studies were included. In total there were 510 patients of which 256 had local PRP injection and 254 without. The average age was 41.6 years, mean time from injury to treatment 5.9 days and mean follow-up at 61 weeks. Biomechanically, there was similar heel endurance, isokinetic strength, calf circumference and range of motion between both groups. In general, there were no differences in patient reported outcomes from all scoring systems used in the studies. Both groups returned to their pre-injured level at a similar time and there were no differences on the incidence of re-rupture (OR 1.13, 95% CI, 0.46-2.80, p = 0.79). CONCLUSION PRP injections for acute Achilles tendon ruptures do not improve medium to long-term biomechanical and clinical outcomes. However, future studies incorporating the ideal application and biological composition of PRP are required to investigate its true clinical efficacy.