The role of Platelet Rich Plasma and other orthobiologics in bone healing and fracture management: A systematic review
Journal of clinical orthopaedics and trauma. 2022;25:101759
BACKGROUND Treatment of large bone defects and fracture healing complications (delayed and non-union) presents a substantial challenge for orthopaedic surgeons. Given that bone healing requires mechanical stability as well as a favourable biological microenvironment, orthobiologics such as Platelet-Rich Plasma (PRP) may have a significant clinical role to play. AIMS To perform a systematic review of the available literature to assess the clinical effect of PRP, with or without other orthobiologics, on bone healing. METHOD Two independent reviewers performed the literature search based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Clinical studies of any evidence, assessing effect of PRP with or without other orthobiologics on bone healing, were included. A qualitative analysis was carried out on the clinical and radiological outcomes reported. RESULT 27 articles with 1631 patients (mean age = 43.56, 57.1% male, mean follow-up = 17.27 months) were included in the qualitative. Of the 27 studies, 13 dealt with fracture complications (delayed or non-unions), 7 with acute fracture healing, 4 with tibial osteotomies and lengthening procedures and 3 with lumbar spine pathology. 18/27 studies showed a clinical benefit of PRP, 8/27 showed no significant effect, and 1/27 showed a worse outcome with PRP. CONCLUSION Our review suggests PRP may play a clinical role in bone healing but further randomised controlled trials (RCTs) using standardised outcomes should be performed to establish its efficacy.
Effects of Platelet-Rich Plasma on Clinical Outcomes After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis
Orthopaedic journal of sports medicine. 2022;10(1):23259671211061535
BACKGROUND Many studies have documented the use of platelet-rich plasma (PRP) alongside anterior cruciate ligament (ACL) reconstruction (ACLR) in the management of ACL injury, but evidence on the benefits of PRP in improving the clinical outcomes of ACLR is inconsistent. PURPOSE To help in our understanding, we undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated the effects of PRP on patient-reported functional scores, the clinical assessments of knee function and structure, and complications. STUDY DESIGN Systematic review; Level of evidence, 1. METHODS We searched 9 online databases for RCTs published in English or Chinese that examined the effects of PRP on ACLR. The primary outcome measures were visual analog scale (VAS) for pain and International Knee Documentation Committee (IKDC) scores. The secondary outcomes included KT-1000 arthrometer, pivot-shift test, Lysholm and Tegner scores, tunnel widening, graft characterization, and complications. Subgroup analyses were performed according to time of assessments. Fixed- and random-effects models were selected for data analysis. RESULTS A total of 14 studies were included. When PRP was injected to graft tunnels, the pooled VAS scores of the 2 groups were similar (P = .31), and the subgroup analysis found that VAS and IKDC only improved at 3 months postoperatively (P = .0003 and P < .00001, respectively). When PRP was used at the bone-patellar tendon-bone harvest sites, VAS was decreased in the first 6 months postoperatively (P < .00001), whereas IKDC score was not remarkably different (P = .07). After PRP injection, Lysholm scores at 3 months postoperatively was different between the 2 groups (P < .00001), but the Tegner scores (P = .86), KT-1000 measurements (P = .12), the positive rate of pivot-shift test (P = .64), the enlargement of tunnels (femoral, P = .91; tibial, P = .80), and the characterization of grafts (P = .05) were not different. No difference in complications was found in either group. CONCLUSION PRP applied alongside ACLR could reduce postoperative pain and improve knee function in the short and medium terms but is ineffective in the long term. PRP does not improve knee stability and the enlargement of tunnels and does not accelerate the healing of grafts. Further studies would be required.
The Adjunctive Use of Leucocyte- and Platelet-Rich Fibrin in Periodontal Endosseous and Furcation Defects: A Systematic Review and Meta-Analysis
Materials (Basel, Switzerland). 2022;15(6)
The aim of this systematic review of randomized controlled trials was to evaluate the adjunctive use of leucocyte- and platelet-rich fibrin (L-PRF) in periodontal endosseous and furcation defects, as compared without L-PRF. The endosseous defect group was subclassified into: L-PRF/open flap debridement (L-PRF/OFD) versus OFD, L-PRF/osseous graft (L-PRF/OG) versus OG, L-PRF/Emdogain (L-PRF/EMD) versus EMD, and L-PRF/guided tissue regeneration (L-PRF/GTR) versus GTR. The furcation defect group was subclassified into L-PRF/OFD versus OFD, and L-PRF/OG versus OG. Mean difference, 95% confidence intervals and forest plots were calculated for probing pocket depth (PPD), clinical attachment level (CAL) and radiographic defect depth (DD). Nineteen studies concerning systemically healthy non-smokers were included. The results of this systematic review and meta-analysis showed in two- and/or three-wall endosseous defects that the adjunctive use of L-PRF to OFD or OG was significantly beneficial for PPD reduction, CAL gain and DD reduction, as compared without L-PRF. Furthermore, the data showed that for two- and/or three-wall endosseous defects, the adjunctive use of L-PRF to GTR was significantly beneficial for CAL and DD improvement, whereas adding L-PRF to EMD had no significant effect, and that for class II furcation defects, the addition of L-PRF to OFD was significantly beneficial for PPD, CAL and DD improvement, whereas the addition of L-PRF to OG was significantly clinically beneficial. In conclusion, this systematic review and meta-analysis found that there was significant clinical and radiographic additive effectiveness of L-PRF to OFD and to OG in two- and/or three-wall periodontal endosseous defects of systemically healthy non-smokers, as compared without L-PRF.
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.
The use of advanced platelet-rich fibrin after surgical removal of mandibular third molars: a systematic review and meta-analysis
International journal of oral and maxillofacial surgery. 2022
The objective of this systematic review was to test the hypothesis of no difference in recovery following surgical removal of mandibular third molars with the application of advanced platelet-rich fibrin (A-PRF) in the extraction socket compared with alternative biomaterials or natural wound healing. A search of MEDLINE (PubMed), Embase, Cochrane Library, and Scopus was conducted. Human randomized controlled trials published in English up until December 31, 2020 were included. Outcome measures were pain, facial swelling, trismus, soft tissue healing, alveolar osteitis, and quality of life; these were evaluated by descriptive statistics and meta-analysis including 95% confidence intervals (CI). Four studies with a low or moderate risk of bias fulfilled the inclusion criteria. A-PRF resulted in significantly lower pain scores when compared with leucocyte platelet-rich fibrin or natural wound healing after 2 days (-16.8, 95% CI -18.9 to -14.7), 3 days (-12.1, 95% CI -13.4 to -10.7), and 7 days (-1.9, 95% CI -2.9 to -0.9). A-PRF seems to have a negligible effect on facial swelling and trismus and some beneficial effect on soft tissue healing. Alveolar osteitis and quality of life were not assessed. The included studies were characterized by considerable heterogeneity and confounding variables. Thus, the level of evidence appears to be inadequate for clinical recommendations according to the focused question.
Effectiveness of Platelet-Rich Plasma for Patients With Carpal Tunnel Syndrome: A Systematic Review and meta-Analysis of Current Evidence in Randomized Controlled Trials
Frontiers in pharmacology. 2022;13:834213
Background: Recently, there was a series of clinical studies focusing on local injection of platelet-rich plasma (PRP) for treatment of patients with carpal tunnel syndrome (CTS). However, the safety and efficacy of PRP in these CTS patients remains controversial. Therefore, we performed a systematic review to compare PRP with other conservative treatments in treatment of CTS patients. Methods: We systematically searched from electronic databases (Cochrane, PubMed, Web of Science, and EMBASE) up to 10 December 2021. The data of clinical results were extracted and analyzed by RevMan Manager 5.4. Results: Finally, eight randomized controlled studies, involving 220 CTS patients undergoing local injection of PRP were enrolled in this systematic review. All enrolled trials were considered to be of high quality. In the short-term efficacy, the PRP group was significantly lower in symptom severity scale (SSS) compared with the control group (MD = -2.00; 95% CI, -3.15 to -0.85; p = 0.0007; I(2) = 0%). In the mid-term efficacy, the PRP group was significantly effective than the control group in the visual analogue scale (MD = -0.63; 95% CI, -1.22 to -0.04; p = 0.04; I(2) = 61%), SSS (MD = -3.56; 95% CI, -4.93 to -2.18; p < 0.00001; I(2) = 0%), functional status scale (MD = -2.29; 95% CI, -3.03 to -1.56; p < 0.00001; I(2) = 45%), sensory peak latency (MD = -0.39; 95% CI, -0.58 to -0.19; p = 0.0001; I(2) = 0%) and cross-sectional area of median nerve (MD = -0.20; 95% CI, -0.31 to -0.10; p = 0.0002; I(2) = 0%). In the mid-long-term efficacy, the PRP group was only significantly lower in SSS compared with the control group (MD = -2.71; 95% CI, -4.33 to -1.10; p = 0.001; I(2) = 38%). Conclusion: Local PRP injection is more effective than other conservative treatments in terms of mid-term efficacy in relieving pain, improving wrist function and symptoms, reducing MN swelling, and partially improving electrophysiological indicators. However, the long-term adverse side and consensus on standardization of PRP in CTS patients still need further large-scale trials.
The use of platelet-rich plasma therapy in treating tennis elbow: A critical review of randomised control trials
Journal of clinical orthopaedics and trauma. 2022;32:101965
Tennis elbow (TE) is a painful and debilitating condition of the elbow. Recently, the use of orthobiologics, such as platelet-rich-plasma (PRP), has been proposed to promote tendon regeneration. Despite their popularity, there is a paucity of updated reviews on the use of PRP compared with other treatment modalities for treating TE. The aim of this review is to summarise high quality studies that compare the use of PRP therapy with other therapies for TE and to identify areas where further research is warranted. This systematic review was performed in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search of PubMed, Scopus and Cochrane Library databases was undertaken in May 2021. Articles were screened for the following criteria: randomised control trials (RCTs) involving PRP in at least one of the treatment arms for tennis elbow. The quality of the RCTs included were analysed for their risk of bias using the modified Cochrane Collaboration Risk of Bias Assessment Tool for randomised trials. A total of 20 RCTs of which 1520 TE patients were analysed. The RCTs included in this review compared PRP with various treatment modalities routinely used in clinical practice such as physiotherapy, steroid injections, Autologous Whole Blood (AWB) and surgical interventions. With regards to the quality of RCTs, collectively, selection bias was found to be low risk however, performance bias in terms of blinding of participants and personnel performed poorly. Of the 20 RCTs, only 5 studies were classified as low risk of bias. In these 5 studies, 2 RCTs compared PRP with steroids and reported contrasting results, 1 RCT compared PRP with AWB injections which reported both to be similarly efficacious, 3 RCTs included a placebo group and only 1 reported superior effects with PRP. There are 2 main types of PRP classified according to the number of pro-inflammatory leukocyte i.e. leukocyte-rich and leukocyte-poor PRP. However, only 8 studies documented the formulation of PRP used. While the heterogeneity of PRP formulations could in-part explain the reported differences in outcomes, overall there is limited robust evidence to recommend PRP therapy for TE. Further research is required to establish the optimal formulation and administration of PRP injections. Proper documentation of TE patients need to be standardised before concrete recommendations on the use of PRP therapy may be offered.
A Systematic Review on the Effect of Common Medications on Platelet Count and Function: Which Medications Should Be Stopped Before Getting a Platelet-Rich Plasma Injection?
Orthopaedic journal of sports medicine. 2022;10(4):23259671221088820
BACKGROUND Platelet-rich plasma (PRP) exerts its effect through the release of growth factors and cytokines from the platelet concentrate. Certain medications may affect platelet count or function, resulting in decreased efficacy of PRP injections. PURPOSE To systematically review the literature regarding common medications and their effects on platelets to establish guidelines for which medications should be stopped before obtaining a PRP injection. STUDY DESIGN Systematic review; Level of evidence, 2. METHODS This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search for studies assessing the effect of common medications on platelet count or platelet function was performed of the PubMed, Cochrane Library, Web of Science, and OpenGrey databases. Inclusion criteria were as follows: drug studied was aspirin, acetaminophen, a nonsteroidal anti-inflammatory drug (NSAID), a statin, or gabapentin; human participants; and article in the English language. Risk of bias was assessed using the Cochrane Risk of Bias tool and the Risk of Bias in Non-randomised Studies-of Interventions tool. RESULTS A total of 1711 studies were identified through the initial search, with 20 studies meeting all inclusion criteria. No studies involving gabapentin met all inclusion criteria. Patients treated with aspirin (268 patients) or acetaminophen (13 patients) showed a significant decrease in platelet aggregation. Statin therapy (73 patients) did not result in a significant decrease in platelet aggregation. Patients who took NSAIDs (172 patients) demonstrated significantly decreased platelet aggregation only when treated with nonselective formulations. Those treated with cyclooxygenase (COX)-2-selective NSAIDs showed no significant difference in platelet aggregation. Treatment with aspirin, acetaminophen, statins, or NSAIDs did not lead to a significant decrease in platelet count. CONCLUSION Aspirin, acetaminophen, and nonselective NSAIDs should be considered for suspension before a PRP injection because of their potential to diminish the effects of the injection. COX-2-selective NSAIDs and statins do not need to be withheld before a PRP injection.
Platelet-Rich Plasma as an Alternative to Xenogeneic Sera in Cell-Based Therapies: A Need for Standardization
International journal of molecular sciences. 2022;23(12)
There has been an explosion in scientific interest in using human-platelet-rich plasma (PRP) as a substitute of xenogeneic sera in cell-based therapies. However, there is a need to create standardization in this field. This systematic review is based on literature searches in PubMed and Web of Science databases until June 2021. Forty-one studies completed the selection criteria. The composition of PRP was completely reported in less than 30% of the studies. PRP has been used as PRP-derived supernatant or non-activated PRP. Two ranges could be identified for platelet concentration, the first between 0.14 × 10(6) and 0.80 × 10(6) platelets/µL and the second between 1.086 × 10(6) and 10 × 10(6) platelets/µL. Several studies have pooled PRP with a pool size varying from four to nine donors. The optimal dose for the PRP or PRP supernatant is 10%. PRP or PRP-derived supernatants a have positive effect on MSC colony number and size, cell proliferation, cell differentiation and genetic stability. The use of leukocyte-depleted PRP has been demonstrated to be a feasible alternative to xenogeneic sera. However, there is a need to improve the description of the PRP preparation methodology as well as its composition. Several items are identified and reported to create guidelines for future research.
The analgesic and anti-hemorrhagic efficacy of platelet-rich plasma in tonsillectomy: A systematic review and meta-analysis of randomized controlled trials
Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2022
AIM: To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the analgesic and anti-hemorrhagic efficacy of platelet-rich plasma (PRP) among patients undergoing tonsillectomy. METHODS PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were screened from inception until July 2021, and updated in December 2021. Risk of bias of the included studies was evaluated according to the Cochrane Collaboration tool. The efficacy endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS Seven RCTs were analyzed, comprising a total of 392 patients. Risk of bias evaluation showed an overall high risk in one RCT, low risk in four RCTs, and some concerns in two RCTs. The pooled results revealed that the mean postoperative pain score was significantly reduced in favor of the PRP group compared with the control group (SMD=-1.38, 95% CI [-1.91, -0.85], p<0.001). Subgroup analysis showed the effect estimate was statistically significant for early postoperative pain (day 0 to day 3), without substantial difference between both groups on late postoperative pain (day 5 and day 7). Moreover, the rate of postoperative hemorrhage was significantly reduced in favor of the PRP group compared with the control group (RR=0.16, 95% CI [0.05, 0.50], p=0.001). Subgroup analysis showed the effect estimate was statistically significant for the rate of primary and secondary hemorrhage. CONCLUSION PRP was associated with significant reduction in postoperative pain and hemorrhage among patients undergoing tonsillectomy. This article is protected by copyright. All rights reserved.