Background. Knee osteoarthritis (KOA) is a common degenerative disease associated with joint dysfunction and pain. Ultrasound-guided radiofrequency (RF) may be a promising therapy in the treatment of chronic pain for KOA patients. Objective. To evaluate the efficacy and safety of ultrasound-guided RF treatment for chronic pain in patients with KOA. Design. A systematic review was conducted, and a meta-analysis was carried out when possible. Setting. We examined the studies evaluating the clinical efficiency of ultrasound-guided RF on chronic pain in KOA population. Method. A systematic review for the efficacy and safety of ultrasound-guided RF treatment for pain management of KOA patients was carried out in PubMed, EMBASE, Cochrane Library, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI) from the date of inception to February 2020, and a meta-analysis was conducted. The primary outcomes of pain intensity (visual analogue scale or numerical rating scale) and knee function [the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)] were evaluated from baseline to various follow-up times by random-effects model. Heterogeneity was assessed by I² statistic and the potential sources of heterogeneity by subgroup and metaregression analyses, respectively. Results. Eight publications with 256 patients were included in the meta-analysis. RF could relieve pain with −4.196 of pooled mean difference and improve knee function by decreasing 23.155 points in WOMAC. Three patients had ecchymosis, two with hypoesthesia and one with numbness after the procedure, and improved within 6 months. Furthermore, study design and treatment target were the sources of heterogeneity by subgroup and metaregression analyses, accounting for 37% and 74% of variances, respectively. Target of genicular nerve achieved better pain relief than intra-articular or sciatic nerve. Sensitivity analysis showed that removal of any single study was unlikely to overturn the findings. Limitations. There were some limitations in the study. Firstly, the small number of relevant studies limited the confidence level of the meta-analysis. Also, the significant heterogeneity may not be explained due to the limited data. Secondly, the direct comparison of two different guidance methods (ultrasound vs. fluoroscopy) for RF therapy is lacking. In addition, the outcomes were blindly assessed in the meta-analysis from all studies according to evaluation of bias, which could affect the reality of the data. Finally, most of the studies only provided short follow-up times, so we could not analyze the long-term effectiveness of ultrasound-guided RF in the treatment of patients with KOA. Conclusions. Ultrasonography is an effective, safe, nonradiative, and easily applicable guidance method for RF in pain relief and functional improvement in KOA patients.
Knee osteoarthritis (KOA) is a very common joint disease and associated with diverse factors including age, obesity, metabolic bone diseases, acute or chronic joint injuries, etc. . The prevalence of KOA ranges from 4.2% to 15.5% and gradually increases with age. Approximately 80% of KOA patients could be diagnosed by imaging at the age of 65 years or older, while only 60% of patients have shown clinical manifestations [2, 3]. Pain and disabilities are the major consequences of KOA, with 25% of patients suffering from severe arthralgia. Furthermore, KOA was ranked 11th among the 291 disabling illnesses worldwide . It is currently believed that failure of chondrocytes to maintain homeostasis between synthesis and degradation of extracellular matrix and subchondral bone leads to osteoarthritis [5–8]. Treatments of KOA include noninvasive therapies such as medication, physical therapy, and rehabilitation as well as minimally invasive strategies from intra‐ or periarticular injections to radiofrequency (RF) . Multiple studies have shown that postoperative RF therapy could accelerate the early rehabilitation of the joints in patients with late stage of KOA after joint replacement surgery [10, 11].
Recently, minimally invasive RF has been extensively used in the treatment of different stages of KOA and has achieved convincing therapeutic benefits. However, conventional RF is routinely guided by X-rays, so it may increase the risk of radiation exposure to the patients and health care providers . Thus, musculoskeletal ultrasonography has become a potential guidance method for RF instead of fluoroscopy in chronic pain management due to its unique advantages [13, 14]. For example, ultrasound guidance is very accurate in peripheral or paraspinal nerve blocks to avoid injury of blood vessels and pleura [15, 16]. The efficacy of ultrasound-guided intervention is associated with many factors such as the settings of ultrasound device, preoperative administration of diagnostic nerve block (DNB), the location of targeted site, the skill of physician, etc. . In recent years, more studies have demonstrated its therapeutic effects on the improvements of soreness, pain, and functional impairments induced by KOA, including case reports, retrospective and prospective uncontrolled studies, and randomized controlled trials (RCTs). However, confounding factors from these studies such as sample size, different methods or procedures may affect the outcomes. Meanwhile, there is no systematic analysis for evaluating the efficacy and safety of ultrasound-guided RF in the treatment of chronic pain in KOA patients. Therefore, we searched several databases from relevant literature to perform a systematic review and meta-analysis to evaluate the efficacy and safety of ultrasound-guided RF for providing preliminary scientific evidence for its clinical application in the treatment of patients with KOA.
A systematic review was conducted, and a meta-analysis was carried out when possible.
2.2. Search Strategy
We systematically searched several electronic databases including PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI) via strategies developed using the appropriate Medical Subject Headings (MeSH) terms from the date of inception to February 2020. Keywords such as “knee osteoarthritis,” “ultrasound guided,” “radiofrequency therapy,” “genicular nerve,” “intra-articular,” and “chronic knee pain” were used. No date, language, or country limitations were applied to the searching.
2.3. Inclusion Criteria
The inclusion criteria for the meta-analysis were as follows: (1) human clinical trials with or without control groups and cointervention were allowed if the trial was performed equally to both arms; (2) patients were diagnosed with KOA and suffered from chronic pain without satisfying pain relief by conservative therapies; (3) patients received RF therapy such as pulsed radiofrequency (PRF) or radiofrequency ablation (RFA); (4) minimally invasive procedure was completed under the guidance of ultrasound; and (5) necessary evaluation index was provided before and after RF therapy, for pain intensity and knee function including visual analogue scale (VAS), numerical rating scale (NRS), Oxford Knee Score (OKS), or Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and for quality of life including 36-Item Short-Form Health Survey (SF-36).
2.4. Exclusion Criteria
The exclusion criteria for the meta-analysis were as follows: (1) full text is not available; (2) patients received total knee arthroplasty (TKA) or other knee surgery; (3) case report; (4) studies with insufficient data or uncompleted RCT; and (5) studies with doubtful data such as illogical outcomes without reasonable explanation.
2.5. Study Selection
After targeted publications were found from different databases, the duplicates were removed first by two experienced investigators independently. Next, irrelevant studies were excluded by further scanning the title and abstract of publication by the inclusion criteria, and then the full text of remaining study was carefully screened to identify eligibility according to the exclusion criteria. Any uncertainty or disagreements were finally resolved via discussion between the two investigators and consulted with the third investigator to reach consensus.
2.6. Data Extraction
Two investigators independently extracted relevant data from each study including the first and corresponding authors, year of publication, country, study design, sample size, demographic characteristics (age and gender), grade of radiologic KOA (Kellgren–Lawrence grading system), follow-up time, type of RF, ultrasound transducer parameter, treatment targets and controls, primary outcomes such as the scores of pain intensity (VAS or NRS) and knee function (WOMAC or Lysholm knee scoring scale) at baseline and available follow-up times, complications or adverse effects, conclusion, and limitations. We contacted the first and/or corresponding authors of study to verify any unclear information and data by e-mails, and the data were considered to be irretrievable without a reply from the authors. All the information was recorded in a prepared spreadsheet, and data were fully analyzed after collection.
2.7. Quality Assessment
The quality and risk of bias for each study were independently assessed by at least two examiners. Additional investigators were consulted when discrepancies were present. RCTs were assessed by the criteria from the Cochrane Handbook for Systematic Reviews of Interventions . The potential sources of bias include random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other bias were judged as “low risk,” “high risk,” or “unclear risk,” respectively. For nonrandomized studies, different biases were determined by the criteria according to “Assessing the Risk of Bias of Individual Studies in Systematic Reviews of Health Care Interventions” . This specific form contains 9 questions, and each question represents a potential source of bias. Positive answer indicates low risk of bias, while negative answer means high risk of bias. Newcastle-Ottawa Scale (NOS) criteria were also used for reference .
2.8. Statistical Analysis
One of the primary outcomes from the studies was the pain intensity of patients as reported as the VAS (0–10 or 0–100 mm) or NRS (0–10) in different studies. To standardize the pain scale, the VAS (0–10 cm) was equivalent to the NRS (0–10) and transformed the scale from 0–10 cm to 0–100 mm. The 95% confidence interval (CI) for the difference in means was used to measure the scores of pain and knee function (WOMAC). For each analysis, the heterogeneity test was performed with I² statistics to measure the degree of data inconsistency as I² > 50% being statistically significant between studies. Data were also analyzed with the random-effects model for high heterogeneity. Subgroup analysis was conducted for study design (RCT vs. prospective vs. retrospective study), treatment target (intra-articular vs. genicular vs. sciatic nerve), the performance of DNB, and follow-up period (0 vs. 4, 12, or 24 weeks). Metaregression analyses were performed to evaluate the sources of heterogeneity based on all the covariates including age and gender in subgroup analysis. Sensitivity analysis was conducted to evaluate the impact of every single study on the pooled mean difference (MD). In addition, the publication bias was evaluated by Begg and Mazumdar rank correlation test and Egger’s regression test [21, 22]. Comprehensive meta-analysis (CMA version 3.0, Biostat, Englewood, NJ, USA) was used to analyze the pooled data.
3.1. Study Selection
A total of 157 publications were identified from six electronic databases and 117 studies for further screening after removing 40 duplicates. Eighty-four irrelevant studies were removed through screening the titles and abstracts of publications, and 25 additional studies were excluded by exclusion criteria via full-text screening. Finally, eight eligible publications were included in the study of meta-analysis including 3 RCTs, 3 prospective trials, and 2 retrospective studies [23–30]. The screening method and results of the relevant studies are illustrated in Figure 1.