Leukocyte and platelet rich fibrin in the management of medication-related osteonecrosis of the jaw: A systematic review and meta-analysis
Muñoz-Salgado A, Silva FF, Padín-Iruegas ME, Camolesi GC, Bernaola-Paredes WE, Veronese HR, Celestino MD, Filho WJ, Lorenzo-Pouso AI, Pérez-Sayáns M
Medicina oral, patologia oral y cirugia bucal. 2023
BACKGROUND Osteonecrosis of the jaw (ONJ) has a frequent adverse effect after the administration of nitrogenous bisphosphonates, as non-nitrogenous bisphosphonates are metabolized more rapidly and would produce this effect to a lesser extent. The objective of this study is to analyze the results obtained in the literature with the use of L-PRF in the treatment of ONJ through a systematic review and meta-analysis. MATERIAL AND METHODS Medline (via PubMed), Cochrane, Web of Science and Grey Literature Database was screened from which 10 were selected. RESULTS In the meta-analysis with full resolution, combining the use of L-PRF in the treatment of ONJ, a weighted proportion (PP) of 94.3% of complete resolution is obtained (95% CI: 91.2-97.4, p<0.001), with a low degree of heterogeneity, statistically significant (I2 = 29.02%; p<0.001). When analyzing the non-resolution data, a weighted proportion (PP) of 7.7% (95% CI: 3.6-11.9; p<0.001) was obtained with moderate heterogeneity (I2: 41.87%; p=0.112). In the meta-regression, no significant correlation was found between complete resolution and year of publication (intercept = 2.88, p=0.829). In consistency analysis no major changes in PP are identified when any of the studies are eliminated, demonstrating a high reliability in the combined results. CONCLUSION L-PRF alone or in combination with other therapies in treatment of ONJ achieved high percentages of complete lesion resolution (94.3%). In studies where L-PRF is combined with other therapies, and where the effectiveness of the other therapy alone is analyzed, L-PRF has been shown higher percentages of resolution.
Platelet-Rich Plasma Injections are at Least Equivalent to Corticosteroid Injections for Adhesive Capsulitis: A Systematic Review of Prospective Cohort Studies
Nudelman B, Song B, Higginbotham DO, Piple AS, Montgomery WH
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2023
PURPOSE To evaluate the role of platelet-rich plasma (PRP) for adhesive capsulitis (AC) as compared to other injectables. METHODS A literature search was performed on PubMed and Embase online databases identifying articles evaluating injection therapy for the treatment of AC. Inclusion criteria included prospective studies comparing PRP against alternative injectables with a minimum 15 patients in each treatment arm and a minimum 12-week follow-up. Pain scores, range of motion, and function scores were the primary outcomes assessed. RESULTS Five articles met inclusion criteria comparing PRP to corticosteroid or saline injections. There were 157 patients treated with PRP with follow-up duration ranging from three to six months. All five studies demonstrated statistically significant improvement in pain scores, motion, and function scores for patients receiving PRP, corticosteroid, and saline injections. However, PRP was consistently superior on intergroup analyses in all but one study. In four studies, pain and function scores favored PRP over control at final follow-up (range in mean difference for VAS pain score: -2.2 - 0.69, n=5 and SPADI score: -50.5 - -4.0, n=3) while three studies found greater improvement in shoulder motion after PRP (range in mean difference for forward flexion: 0.7 - 34.3 degrees and external rotation -2.3 - 20.4 degrees, n=4). One study found no significant difference between PRP and corticosteroid injections, but noted results were comparable. CONCLUSIONS According to a limited number of prospective studies, PRP injections for AC is at least equivalent to corticosteroid or saline injections and often leads to improved pain, motion, and functional outcomes at 3-6-month follow-up. Given the small number of studies, with design heterogeneity, there is insufficient evidence to routinely recommend PRP for AC. However, the results are promising and do support considering PRP as an adjunct treatment option for AC, especially for patients refractory and/or averse to corticosteroids or alternative treatment modalities.
The Influence of Industry Affiliation on Randomized Controlled Trials of Platelet-Rich Plasma for Knee Osteoarthritis
Ta CN, Vasudevan R, Mitchell BC, Keller RA, Kent WT
The American journal of sports medicine. 2023;:3635465221140917
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.
A Comparative Preliminary Randomized Clinical Study to Evaluate Heavy Bupivacaine Dextrose Prolotherapy (HDP) and Autologous Blood Injection (ABI) for Symptomatic Temporomandibular Joint Hypermobility Disorder
Bhargava D, Sivakumar B, Bhargava PG
Journal of maxillofacial and oral surgery. 2023;22(1):110-118
PURPOSE Temporomandibular joint (TMJ) sub-luxation can have a significant psycho-social impact on a patients' well-being. Several treatment modalities have been described in the literature for the same. The present study was undertaken to investigate the efficacy of heavy bupivacaine-dextrose prolotherapy (HDP) for the peri-articular tissues, superior joint space and the retro-discal area in the patients with symptomatic chronic sub-luxation. MATERIALS AND METHODS A preliminary clinical study was conducted among 60 patients diagnosed with chronic painful sub-luxation of the TMJ. Patients were divided into control group (CG), n = 30, where autologous blood was injected in the superior joint space, peri-capsular tissues and retro-discal area bilaterally as per the predetermined protocol; and the study group (SG), n = 30 patients were administered heavy bupivacaine-dextrose injection bilaterally in the peri-articular tissues, superior joint space and retro-discal area. The efficacy of the treatment was evaluated by assessing pain, maximum inter-incisal opening (MIO), changes in computed tomography scan, magnetic resonance imaging study, number and need for subsequent injections in both the groups. RESULT Among the 60 patients, majority of the patients exhibited successful outcome after both the interventions, ABI and HDP. There was statistically significant reduction in recorded pain score with reduced MIO post-treatment. No morphological changes were noted in the condyle in both the groups. No complications were recorded among the study population. CONCLUSION HDP is a safe and simple modality for treating symptomatic sub-luxation with predictable clinical outcome. Heavy bupivacaine-dextrose can be considered as a prolotherapeutic agent for symptomatic chronic temporomandibular joint sub-luxation with the pharmacological benefit of local anaesthesia and proliferent delivery through the same injection.
The Efficacy of Platelet-Rich Plasma Injection Therapy in the Treatment of Patients with Achilles Tendinopathy: A Systematic Review and Meta-Analysis
Arthur Vithran DT, Xie W, Opoku M, Essien AE, He M, Li Y
Journal of clinical medicine. 2023;12(3)
BACKGROUND Over the past few years, many studies have been conducted to evaluate the effectiveness of platelet-rich plasma (PRP) in treating musculoskeletal conditions. However, there is controversy about its benefits for patients with Achilles tendinopathy. OBJECTIVE This study aimed to investigate whether platelet-rich plasma injections can improve outcomes in patients with Achilles tendinopathy. METHODS A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, Web of Science, China Biomedical CD-ROM, and Chinese Science and Technology Journal databases to identify randomised controlled clinical trials that compared the efficacy of PRP injection in patients with Achilles tendinopathy (AT) versus placebo, published between 1 January 1966 and 1 December 2022. Review Manager 5.4.1 software was used for the statistical analysis, and the Jadad score was used to assess the included literature. Only 8 of the 288 articles found met the inclusion criteria. RESULTS Our work suggests that: The PRP treatment group had a slightly higher VISA-A score than the placebo group at 6 weeks [MD = 1.92, 95% CI (-0.54, 4.38), I(2) = 34%], at 12 weeks [MD = 0.20, 95% CI (-2.65 3.05), I(2) = 60%], and 24 weeks [MD = 2.75, 95% CI (-2.76, 8.26), I(2) = 87%]). However, the difference was not statistically significant. The Achilles tendon thickness was higher at 12 weeks of treatment in the PRP treatment group compared to the control group [MD = 0.34, 95% CI (-0.04, 0.71), p = 0.08], but the difference was not statistically significant. The VAS-improvement results showed no significant difference at 6 and 24 weeks between the two groups, respectively (MD = 6.75, 95% CI = (-6.12, 19.62), I(2) = 69%, p = 0.30), and (MD = 10.46, 95% CI = (-2.44 to 23.37), I(2) = 69%, p = 0.11). However, at 12 weeks of treatment, the PRP injection group showed a substantial VAS improvement compared to the control group (MD = 11.30, 95% CI = (7.33 to 15.27), I(2) = 0%, p < 0.00001). The difference was statistically significant. The return to exercise rate results showed a higher return to exercise rate in the PRP treatment group than the placebo group [RR = 1.11, 95% CI (0.87, 1.42), p = 0.40]; the difference was not statistically significant. CONCLUSION There is no proof that PRP injections can enhance patient functional and clinical outcomes for Achilles tendinopathy. Augmenting the frequency of PRP injections may boost the outcomes, and additionally, more rigorous designs and standardised clinical randomised controlled trials are needed to produce more reliable and accurate results.
Effects of Platelet-Rich Plasma in Tear Size Reduction in Partial-Thickness Tear of the Supraspinatus Tendon Compared to Corticosteroids Injection
Tanpowpong T, Thepsoparn M, Numkarunarunrote N, Itthipanichpong T, Limskul D, Thanphraisan P
Sports medicine - open. 2023;9(1):11
OBJECTIVES Corticosteroid (CS) injection is commonly used in partial-thickness rotator cuff tears to decrease pain. However, this could result in unwanted side effects, such as tendon rupture. Alternatively, platelet-rich plasma (PRP) injection is frequently used to treat tendinopathies because it enhances healing. This study aimed to compare the differences in tear size and functional scores between intralesional PRP and subacromial CS injections. METHODS Patients with symptomatic partial-thickness tears of the supraspinatus tendon who underwent conservative treatment for ≥ 3 months were enrolled. All patients underwent magnetic resonance imaging (MRI) to confirm the diagnosis. Fourteen and 15 patients were randomized to receive intralesional PRP and subacromial CS injections, respectively. Tears were measured in the coronal and sagittal planes. The patients underwent another MRI 6 months after the injection. Tear size was compared between the two MRI results. The American Shoulder and Elbow Surgeons Shoulder score (ASES) and Constant-Murley score (CMS) were also obtained. RESULTS The baseline data were similar between the groups. In the coronal plane, PRP and CS showed tear size reductions of 3.39 mm (P = 0.003) and 1.10 mm (P = 0.18), respectively. In the sagittal plane, PRP and CS showed tear size reductions of 2.97 mm (P = 0.001) and 0.76 mm (P = 0.29), respectively. Functional scores improved 6 months after injection in both groups, but PRP showed better functional scores than CS (P = 0.002 for ASES, P = 0.02 for CS). CONCLUSION Intralesional PRP injection can reduce the tear size in partial-thickness tears of the supraspinatus tendon. Subacromial steroid injection did not significantly affect the tear size. While CS improved functional scores compared with baseline, PRP resulted in better improvement 6 months post-injection. Trial registration Thai Clinical Trials Registry, TCTR20210428004. Registered 28 April 2021-retrospectively registered, TCTR20210428004 .
Comparison of clinical outcome, cartilage turnover, and inflammatory activity following either intra-articular or a combination of intra-articular with intra-osseous platelet-rich plasma injections in osteoarthritis knee: A randomized, clinical trial
Barman A, Bandyopadhyay D, Mohakud S, Sahoo J, Maiti R, Mukherjee S, Prakash S, Roy SS, Viswanath A
BACKGROUND The objective of the study was to determine the changes in clinical outcome (pain and knee activity) and assess bone/ cartilage biomarkers and inflammatory activity in persons with osteoarthritis (OA) knee following a single injection of intra-articular platelet-rich plasma (IA-PRP) and combination of intra-articular, intraosseous PRP (IA+IO-PRP). METHODS This prospective, randomized, single-blind clinical trial was conducted at a tertiary care teaching hospital in India. Ninety-six persons with OA knee with a Kellgren-Lawrence score of 3 were randomized into three groups- Group-I (IA-PRP), Group-II (IA+IO-PRP)], Group-III, [intra-articular normal saline (IA-NS)]. The primary outcome was a visual analog scale (VAS) for pain. The secondary outcomes were the Knee Injury and Osteoarthritis Outcome Score (KOOS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), bone/ cartilage turnover biomarkers [C-telopeptide (CTX-II), N-telopeptide (NTX-I), cartilage oligomeric matrix protein (COMP), N-terminal propeptide of collagen type-IIA (PIIANP), and hyaluronic acid (HA)], ultrasonography (USG) findings of the knee joint. The outcome measures were assessed at baseline, 6, and 12 weeks of follow-up. RESULTS Compared to IA-NS injection, IA-PRP and IA+IO-PRP injections significantly improved VAS-pain and KOOS scores at 6 and 12 weeks. Furthermore, both PRP groups showed a significant reduction in ESR, CRP, and CTX-II at 12 weeks following PRP injections. In addition, at 12 weeks, the IA+IO-PRP group showed a significant reduction (p=0.009) in NTX-I level. Persons in the IA+IO-PRP group reported significant reductions in the synovial-effusion and infra-patellar bursitis. CONCLUSIONS Significant clinical improvements were noticed following IA-PRP and IA-IO-PRP injections compared to IA-NS injections. Both PRP groups reported a significant reduction in ESR, CRP, and CTX-II levels at 12 weeks. Persons in the IA+IO-PRP group reported significant changes in u-NTX-I level and knee-USG findings.
Platelet-rich plasma injection in the treatment of patellar tendinopathy: a systematic review and meta-analysis
Barman A, Sinha MK, Sahoo J, Jena D, Patel V, Patel S, Bhattacharjee S, Baral D
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.
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
Barman A, Prakash S, Sahoo J, Mukherjee S, Maiti R, Roy SS
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.
Leukocyte-Rich versus Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Trial
Di Martino A, Boffa A, Andriolo L, Romandini I, Altamura SA, Cenacchi A, Roverini V, Zaffagnini S, Filardo G
The American journal of sports medicine. 2022;:3635465211064303
BACKGROUND Platelet-rich plasma (PRP) is gaining large interest in clinical practice as a minimally invasive injective treatment for knee osteoarthritis (OA). Different preparation methods are available, and the presence of leukocytes, deemed detrimental in some preclinical studies, is one of the most debated aspects regarding PRP efficacy. PURPOSE To compare the safety and effectiveness of leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) for the treatment of knee OA. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS A total of 192 patients with symptomatic knee OA (Kellgren-Lawrence grade 1-3) were randomly allocated to 3 weekly injections of LR-PRP or LP-PRP. LP-PRP was obtained with a filter for leukodepletion. LR-PRP and LP-PRP were divided into aliquots of 5 mL, with a mean platelet concentration of 1146.8 × 10(9)/L and 1074.9 × 10(9)/L and a mean leukocyte concentration of 7991.4 × 10(6)/L and 0.1 × 10(6)/L, respectively. Patients were evaluated at baseline and thereafter at 2, 6, and 12 months for the primary outcome, the International Knee Documentation Committee (IKDC) subjective score; and for secondary outcomes, the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol-visual analog scale (EQ-VAS), and Tegner score. RESULTS No differences between groups were observed in terms of absolute values or improvement of the clinical scores across all follow-up intervals. The mean IKDC subjective score at baseline and 12 months improved from 45.6 to 60.7 in the LR-PRP group as compared with 46.8 to 62.9 in the LP-PRP group (P = .626). No severe adverse events were described in either group, although 15 mild adverse events (knee pain or swelling) were reported: 12.2% for LR-PRP and 4.7% for LP-PRP (P = .101). No statistically significant difference was also found between LR-PRP and LP-PRP in terms of failures (7.8% vs 3.5%, P = .331). CONCLUSION This double-blind randomized trial showed that 3 intra-articular LR-PRP or LP-PRP injections produced similar clinical improvement in the 12 months of follow-up in patients with symptomatic knee OA. Both treatment groups reported a low number of adverse events, without intergroup differences. The presence of leukocytes did not significantly affect the clinical results of PRP injections. REGISTRATION NCT02923700 (ClinicalTrials.gov identifier).