BACKGROUND: With the continuous development of clinical medicine, an increasing number of non-pharmacological interventions have been applied for the treatment of knee osteoarthritis (KOA), with the results of several recent randomized controlled trials (RCTs) showing that a variety of externally-applied, non-pharmacological interventions (EANPI) can improve symptoms and inflammation in patients with KOA. However, the relative benefits and disadvantages of non-drug therapies remain uncertain, and an optimal treatment strategy has not yet been determined.
OBJECTIVE: This study applied network meta-analysis (NMA) to compare and rank the effectiveness of EANPI on the short- and long-term clinical symptoms and inflammatory cytokine levels in patients with KOA.
METHODS: Two independent researchers searched online databases and performed manual retrieval of related citations to identify RCTs that met the selection criteria for the network meta-analysis. These researchers retrieved studies indexed from database inception to August 2023 and performed data extraction and assessment of the risk of bias.
RESULTS: The analysis included 80 RCTs involving 8440 participants and nine externally-applied, non-pharmacological therapies, namely extracorporeal shock wave, radiofrequency, acupotomy, laser therapy, Tuina therapy, kinesio taping, electroacupuncture, platelet-rich plasma injection, and ozone therapy. The treatment courses ranged from 1 to 12 weeks, with follow-up periods ranging from 4 to 24 weeks. The results of the NMA indicated that each non-drug therapy was superior to sham intervention in improving all outcome indicators. Except for the visual analog scale (VAS) and Western Ontario MacMaster (WOMAC) pain outcomes, all non-drug therapies had better efficacy than pharmacological treatments. For short-term VAS and tumor necrosis factor-alpha (TNF-α), extracorporeal shock wave performed better than other therapies (90.2% and 85.2% respectively). Radiofrequency therapy may be the most promising method to reduce long-term VAS, short- and long-term WOMAC pain, and interleukin (IL)-1β level (84.8%, 97.8%, 90.1%, 94.8% respectively). Tuina therapy may be a significant choice for short- and long-term outcomes of WOMAC function and range of motion (ROM).
CONCLUSIONS: The results of the comprehensive comparison of the outcome indicators in 9 different EANPI indicated that radiofrequency and Tuina therapy were more effective and consistently ranked high in improving clinical symptoms in the short and long term. Radiofrequency is effective at relieving pain, and Tuina therapy can be given priority for treatment when hypofunction is the main symptom. EANPI to improve pain symptoms may be related to the regulation of inflammatory cytokine levels, which may be a potential mechanism of action.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42023464177.
ABSTRACT: PURPOSE: To review and indirectly compare the outcomes of genicular artery embolization (GAE), radiofrequency (RF) ablation, and intra-articular (IA) injection for the treatment of knee pain secondary to osteoarthritis (OA). MATERIALS AND METHODS: A literature review of the MEDLINE and Cochrane databases was conducted with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement in June 2020. The visual analog scale (VAS) was recorded at baseline and at all available time points for each therapy. Standard mean differences were calculated at each time point and compared between treatments to assess the magnitude of the treatment effect. RESULTS: All 3 treatments demonstrated significant differences in VAS scores after therapy. RF ablation produced the greatest significant mean reduction in relative VAS score from baseline at 1 year of follow-up (mean, 0.49; 95% confidence interval, 0.4-0.59; P = .03). GAE reported the most significant reductions in VAS scores across all measured time points. Overall, the comparison did not demonstrate a significant difference in VAS scores among patients receiving IA injections, RF ablation, and GAE. CONCLUSIONS: The current evidence does not suggest a significant difference in outcomes among IA injection, RF ablation, and GAE for knee pain secondary to OA.
CONTEXT: Amid extensive debate, evidence surrounding the use of platelet-rich plasma (PRP) for musculoskeletal injuries has rapidly proliferated, and an overall assessment of efficacy of PRP across orthopaedic indications is required.
OBJECTIVES: (1) Does PRP improve patient-reported pain in musculoskeletal conditions? and (2) Do PRP characteristics influence its treatment effect?
DATA SOURCES: MEDLINE, EMBASE, Cochrane, CINAHL, SPORTDiscus, and Web of Science libraries were searched through February 8, 2017. Additional studies were identified from reviews, trial registries, and recent conferences.
STUDY SELECTION: All English-language randomized trials comparing platelet-rich therapy with a control in patients 18 years or older with musculoskeletal bone, cartilage, or soft tissue injuries treated either conservatively or surgically were included. Substudies of previously reported trials or abstracts and conference proceedings that lacked sufficient information to generate estimates of effect for the primary outcome were excluded.
STUDY DESIGN: Systematic review and meta-analysis.
LEVEL OF EVIDENCE: Level 1.
DATA EXTRACTION: All data were reviewed and extracted independently by 3 reviewers. Agreement was high between reviewers with regard to included studies.
RESULTS: A total of 78 randomized controlled trials (5308 patients) were included. A standardized mean difference (SMD) of 0.5 was established as the minimum for a clinically significant reduction in pain. A reduction in pain was associated with PRP at 3 months (SMD, -0.34; 95% CI, -0.48 to -0.20) and sustained until 1 year (SMD, -0.60; 95% CI, -0.81 to -0.39). Low- to moderate-quality evidence supports a reduction in pain for lateral epicondylitis (SMD, -0.69; 95% CI, -1.15 to -0.23) and knee osteoarthritis (SMD, -0.91; 95% CI, -1.41 to -0.41) at 1 year. PRP characteristics did not influence results.
CONCLUSION: PRP leads to a reduction in pain; however, evidence for clinically significant efficacy is limited. Available evidence supports the use of PRP in the management of lateral epicondylitis as well as knee osteoarthritis.
INTRODUCTION: Knee osteoarthritis (KOA) is a significant health problem with lifetime risk of development estimated to be 45%. Effective nonsurgical treatments are needed for the management of symptoms.
METHODS: We designed a network meta-analysis to determine clinically relevant effectiveness of nonsteroidal anti-inflammatory drugs, acetaminophen, intra-articular (IA) corticosteroids, IA platelet-rich plasma, and IA hyaluronic acid compared with each other as well as with oral and IA placebos. We used PubMed, EMBASE, and Cochrane Central Register of Controlled Trials to perform a systematic search of KOA treatments with no date limits and last search on October 7, 2015. Article inclusion criteria considered the following: target population, randomized controlled study design, English language, human subjects, treatments and outcomes of interest, ≥30 patients per group, and consistent follow-up. Using the best available evidence, two abstractors independently extracted pain and function data at or near the most common follow-up time.
RESULTS: For pain, all active treatments showed significance over oral placebo, with IA corticosteroids having the largest magnitude of effect and significant difference only over IA placebo. For function, no IA treatments showed significance compared with either placebo, and naproxen was the only treatment showing clinical significance compared with oral placebo. Cumulative probabilities showed naproxen to be the most effective individual treatment, and when combined with IA corticosteroids, it is the most probable to improve pain and function.
DISCUSSION: Naproxen ranked most effective among conservative treatments of KOA and should be considered when treating pain and function because of its relative safety and low cost. The best available evidence was analyzed, but there were instances of inconsistency in the design and duration among articles, potentially affecting uniform data inclusion.
INTRODUCTION: Platelet rich plasma (PRP) has been suggested to be effective in the management of knee osteoarthritis. Review of current literature reveals conflicting evidence regarding the benefits of PRP in treating knee OA. Preclinical evidence supports the use of PRP injections to promote a favorable environment for joint tissue healing, targeting not only cartilage but also synovial and meniscal tissues which has a positive effect on delaying the progression of OA. Growth factors found in platelet granules are postulated to influence outcomes in knee OA and after total knee arthroplasty (TKA).
METHODOLOGY: A systematic review of studies investigating the use of PRP in knee osteoarthritis and following TKA, was performed by searching the following databases for randomised clinical trials and pseudo-randomised clinical and comparative trials comparing the use of PRP to treat knee osteoarthritis and following TKA; MedLine, EMBASE, Science Direct, PubMed, and the Cochrane Library. The primary outcomes were patient reported measures including pain (visual analog scale (VAS)), quality of life scores, and knee function.
RESULTS: A total of 2328 participants were analyzed across 17 included studies and pooled results showed a statistically significant reduction in pain in favor of PRP following TKA but not in non-surgical management of knee OA (P < 0.0001 and 0.13 respectively). No clinical benefit of PRP was found on quality of life and knee function (P = 0.07 and 0.05) following TKA, although a statistical improvement in knee function was demonstrated in patients with knee OA after PRP injection (P < 0.0001). There was no statistically significant clinical benefit of PRP on secondary outcomes including wound scores and length of hospital stay (p = 0.33 and 0.31, respectively). There was no statistically significant difference in respect to blood loss and overall symptoms in favor of PRP compared to control group following TKA (p = 0.37).
CONCLUSION: This systematic review demonstrated no long-term statistically significant improvement in patient validated outcomes and secondary outcomes both in patients with knee OA or following TKA for OA. However PRP has been shown to have short to medium-term benefits in pain control after TKA and activities of daily living in patients with OA.
INTRODUCTION: The aim of this study was to conduct a systematic review in order to examine the effectiveness of ozone therapy on knee osteoarthritis. The objectives were to evaluate the effect over time of ozone therapy in terms of knee pain, functional improvement and radiographic progression.
MATERIAL AND METHODS: A search was carried out on PubMed, Embase, Cochrane Library, Scopus and Web of Science databases to identify randomized and controlled studies focusing on this association. The following descriptors were used in English: ozone therapy, knee osteoarthritis. A descriptive summary and quality assessment was made of all studies included for analysis.
RESULTS: Six randomized and controlled studies were identified. The risk of bias assessment demonstrated that one study was considered as having a moderate risk of bias and the remainder a high risk of bias. No quantitative analysis of the data was performed, as the studies included were not sufficiently homogeneous. The participants in the studies were generally elderly patients with mild to moderate knee osteoarthritis.
DISCUSSION: The variability of ozone therapy and the comparators demonstrates that there is no standardized therapy. Few studies reported adverse effects, and where they occurred, they were mild and associated with the procedure.
CONCLUSION: Ozone therapy proved effective in the short-term in relation to placebo and when combined with hyaluronic acid, but it was not superior to other current treatments. More randomised and controlled studies are needed to evaluate the risks/benefits of ozone therapy, both in the short term and the medium/long term.
PURPOSE: Platelet-rich plasma (PRP) and hyaluronic acid (HA) have been increasingly used in recent years to treat knee osteoarthritis (OA). However, whether PRP is superior to HA is controversial.
METHODS: We conducted an electronic search of PubMed, Embase, ScienceDirect, and Cochrane library. The pooled data were analyzed using RevMan 5.1.
RESULTS: Three prospective and ten randomized trials were identified. PRP injections reduced pain more effectively than HA injections in OA of the knee at 6 months (mean difference [MD]=-14.18; 95% confidence interval [CI]: -26.12 to -2.23; P=0.02; I2=95%) and 12 months (MD=-15.25; 95% CI: -22.17 to -8.32; P<0.01; I2=81%) of follow-up evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, while the VAS showed no significant difference at 3 months (MD=-0.98; 95% CI: -2.55 to 0.59; P=0.22; I2=90%) and 6 months (MD=-0.82; 95% CI: -1.80 to 0.16; P=0.1; I2=83%). Additionally, similar results were observed for the function recovery according to the WOMAC function score and EuroQol-visual analog scales.
CONCLUSION: The intra-articular injection of PRP was not obviously superior to HA in knee OA. Due to the limited quality and data of the evidence currently available, more high-quality randomized controlled trials are required.
OBJECTIVE: Knee osteoarthritis (OA) is a common disease, imposing a great burden through pain and decreased function. Numerous methods have been tested for pain management in knee OA and the optimal method is currently still under debate. We performed a meta-analysis from randomized controlled trials (RCTs) to compare the efficacy and safety of intra-articular hyaluronic acid (HA) and oxygen-ozone in the treatment of knee OA.
METHODS: Electronic databases included PubMed, Embase, web of science and the Cochrane Library. High quality RCTs comparing HA with oxygen-ozone in the treatment of knee OA were selected. We assessed statistical heterogeneity for each RCT with the use of a standard Chi2 test and the I2 statistic. Quality assessment was performed by using Cochrane Collaboration's tool. All data were carried out with Stata 14.0 software.
RESULTS: A total of four RCTs including 289 patients were included. The present meta-analysis indicated that there was a significant difference between groups regarding the visual analog scale (VAS) and WOMAC stiffness and function. The improvements in WOMAC pain were similar. No significant difference in adverse events occurrence was observed.
CONCLUSION: Intra-articular injection of HA was associated with a significantly reduction in VAS score at 1st month compared to oxygen-ozone. And there was significant differences in WAMAC stiffness, and function at 6-month follow-up between groups. Based on the current evidence available, more RCTs are needed for further investigation.
BACKGROUND: In this study, we evaluated whether platelet-rich plasma (PRP) is superior to hyaluronic acid (HA) in the treatment of knee osteoarthritis.
METHODS: The Cochrane Central Register of Controlled Trials, PubMed, and Embase databases were searched for English-language, human in vivo studies on the treatment of symptomatic knee osteoarthritis with intra-articular PRP compared with HA. The following keywords were used for the search: "platelet-rich plasma," "PRP," "platelet-rich fibrin," "PRF," "platelet," "plasma," "arthritis," "osteoarthritis," "gonarthrosis," and "degeneration."
RESULTS: Seven articles reporting 908 patients and 908 knees were analyzed, including 44% men and 56% women with a mean age of 59.8 years. All studies met the minimal clinically important difference criteria and showed statistically significant improvements in clinical outcomes, including pain, physical function, and stiffness, with PRP treatment. All except two studies showed significant differences between PRP and HA regarding clinical outcomes of pain and function.
CONCLUSIONS: PRP intra-articular injection of the knee may be an effective alternative treatment for knee OA, especially in patients with mild knee OA. Although some studies suggested that the effect of PRP was no better than HA, we found that it was no worse. A large, multicenter, randomized trial is needed to further assess the efficacy of PRP treatment for patients with knee OA.
TRIAL REGISTRATION: PROSPERO, CRD42016048394 . Registered on October 2, 2016).
BACKGROUND: Pain and limitations in joint mobility associated with knee osteoarthritis (OA) are clinically challenging to manage, and advanced progression of disease can often lead to total knee arthroplasty. Intra-articular injection of hyaluronic acid (HA), also referred to as viscosupplementation, is a non-surgical treatment approach for OA, the effectiveness of which may depend on the HA composition, and the length of time over which it resides in the joint. One of the available options for such therapies includes NASHA (Durolane HA), a non-animal, biofermentation-derived product, which is manufactured using a process that stabilizes the HA molecules to slow down their rate of degradation and produce a unique formulation with a terminal half-life of ~1 month. The objectives of the current review were to assess, in patients with OA of the knee, the efficacy and safety of intra-articular treatment with NASHA relative to control (saline) injections, other HA products, and other injectables (corticosteroids, platelet-rich plasma, mesenchymal stem cells).
METHODS: This systematic evidence review examines patient outcomes following NASHA treatment as described in published data from studies conducted in subjects with knee OA. A Preferred Reporting Items for Systematic Reviews and Meta-analyses-compliant literature search strategy yielded 11 eligible clinical studies with a variety of comparator arms. Outcomes assessed at various time points following intra-articular treatment included measures of pain, function, quality of life, and incidence of treatment-related adverse events (AEs).
RESULTS: The available evidence reported for the clinical studies assessed demonstrates sustained and effective relief of knee OA symptoms following a single injection of NASHA. In addition, an excellent biocompatibility profile is observed for NASHA as an intra-articular therapy for OA, as reflected by the low rate of AEs associated with treatment.
CONCLUSION: Treatment with NASHA is an effective and safe single-injection procedure, which can be beneficial in the clinical management of knee OA.
With the continuous development of clinical medicine, an increasing number of non-pharmacological interventions have been applied for the treatment of knee osteoarthritis (KOA), with the results of several recent randomized controlled trials (RCTs) showing that a variety of externally-applied, non-pharmacological interventions (EANPI) can improve symptoms and inflammation in patients with KOA. However, the relative benefits and disadvantages of non-drug therapies remain uncertain, and an optimal treatment strategy has not yet been determined.
OBJECTIVE:
This study applied network meta-analysis (NMA) to compare and rank the effectiveness of EANPI on the short- and long-term clinical symptoms and inflammatory cytokine levels in patients with KOA.
METHODS:
Two independent researchers searched online databases and performed manual retrieval of related citations to identify RCTs that met the selection criteria for the network meta-analysis. These researchers retrieved studies indexed from database inception to August 2023 and performed data extraction and assessment of the risk of bias.
RESULTS:
The analysis included 80 RCTs involving 8440 participants and nine externally-applied, non-pharmacological therapies, namely extracorporeal shock wave, radiofrequency, acupotomy, laser therapy, Tuina therapy, kinesio taping, electroacupuncture, platelet-rich plasma injection, and ozone therapy. The treatment courses ranged from 1 to 12 weeks, with follow-up periods ranging from 4 to 24 weeks. The results of the NMA indicated that each non-drug therapy was superior to sham intervention in improving all outcome indicators. Except for the visual analog scale (VAS) and Western Ontario MacMaster (WOMAC) pain outcomes, all non-drug therapies had better efficacy than pharmacological treatments. For short-term VAS and tumor necrosis factor-alpha (TNF-α), extracorporeal shock wave performed better than other therapies (90.2% and 85.2% respectively). Radiofrequency therapy may be the most promising method to reduce long-term VAS, short- and long-term WOMAC pain, and interleukin (IL)-1β level (84.8%, 97.8%, 90.1%, 94.8% respectively). Tuina therapy may be a significant choice for short- and long-term outcomes of WOMAC function and range of motion (ROM).
CONCLUSIONS:
The results of the comprehensive comparison of the outcome indicators in 9 different EANPI indicated that radiofrequency and Tuina therapy were more effective and consistently ranked high in improving clinical symptoms in the short and long term. Radiofrequency is effective at relieving pain, and Tuina therapy can be given priority for treatment when hypofunction is the main symptom. EANPI to improve pain symptoms may be related to the regulation of inflammatory cytokine levels, which may be a potential mechanism of action.
