Effects of blood flow restriction training in patients with knee osteoarthritis: A meta- analysis

doi:10.21203/rs.3.rs-3624321/v1

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Effects of blood flow restriction training in patients with knee osteoarthritis: A meta- analysis

https://doi.org/10.21203/rs.3.rs-3624321/v1

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Background. Knee osteoarthritis (KOA) is a common degenerative disease.Resistance training is considered as an effective approach to reduce the risk of muscle weakness in patients with KOA. Blood flow restriction training (BFRT) with low-load resistance training has better clinical outcomes than low-load resistance training alone. However, the degree of BFRT which works more effectively withlow-load resistance training has not been determined. The purpose of this study is to provide a comprehensive overview of the existing data regarding the impact of blood flow restriction training (BFRT) on quadriceps strength, muscle size, pain, physical function, biomarkers, quality of life, and adverse events in patients with KOA.

Method. A comprehensive search was conducted in five English-language electronic databases to identify randomized controlled trials (RCTs) comparing BFRT with conventional resistance training in patients with KOA. The selection of studies was based on predetermined inclusion and exclusion criteria. The methodological quality and evidence quality of the selected studies were evaluated. The retrieval period for the literature was from the creation of the database to June 2023.

Results. A total of six RCTs were included in this meta-analysis, examining the effects of BFRT compared with those of conventional resistance training on KOA. The pooled results indicated a significant difference between the BFRT group and the control group in terms of quadriceps strength (SMD 0.39 (95% CI 0.18, 0.60), p = 0.01) and biomarkers (SMD 1.31 (95% CI 0.73, p = 0.00). However, BFRT did not show a significant difference compared to conventional resistance training in muscle size (ES = −0.47 (95% CI −1.51, 0.58), p = 0.45), pain (SMD −0.02, (95% CI −0.29, 0.25), p = 0.88), physical function (ES −0.09 (95% CI −0.37, 0.20), p = 0.14), quality of life (SMD 0.30 (95% CI −0.13, 0.73), p = 0.30) or adverse events (RR 0.45 (95% CI 0.20, 1.01), p = 0.05).

Conclusions. The evidence reviewed suggests that BFRT may be beneficial for improving muscle strength and biomarkers compared to control training, but it may not be more effective in treating other symptoms of patients with osteoarthritis of the knee, including those related to muscle size, pain, physical function, quality of life, and adverse events. More high-quality evidence is needed to further investigate its therapeutic effects.

blood flow restriction training

osteoarthritis

knee

occlusion training

resistance training

Osteoarthritis is a prevalent chronic degenerative condition affecting middle-aged and elderly men [1]. Osteoarthritis causes the degradation of cartilage, a reduction in joint spaces, and the development of osteophytes [2]. The knee is highly susceptible to this condition, obvious features of which are the loss of articular cartilage and structural changes in the joints [3]. Osteoarthritis is characterized by reduced muscle strength, reduced stability, and decreased function of the joints [4–6]. At present, the most effective treatment for KOA remains undetermined. Nevertheless, interventions aimed at alleviating symptoms and mitigating risk factors seem to delay disease progression, enhance muscular strength, promote physical function recovery, and enhance overall quality of life [7].

Resistance training exercises have been shown to have the potential to augment muscle strength and promote muscle hypertrophy, thereby potentially reducing the risk of KOA [8, 9]. The guidance recommendations put forth by the American College of Sports Medicine (ACSM) emphasize the utmost importance of incorporating these exercises. The minimum resistance exercise intensity required to increase muscle circumference is 70–85% 1-RM (maximum repetitive RM), and the minimum resistance exercise intensity required to increase muscle strength is 60–70 (1-RM) [10]. Although high-intensity exercise is valuable for achieving many benefits, it may not be suitable for individuals who cannot tolerate higher levels of exercise intensity, such as obese, elderly, and rehabilitating individuals. BFRT, which originated in Japan, is also known as pressure training. It is a training method that has emerged in recent years, and it uses adjustable pressure cuffs to cause short-term venous blood reflux in the proximal limbs while combining low-intensity exercise to improve the body’s functional level. By combining low-load resistance training (LLRT) with blood flow restriction (BFRT), similar effects to high-load resistance training can be achieved, such as beneficial muscle adaptation. Good effects in improving muscle quality and strength can also be achieved, promoting rehabilitation and preventing disuse-induced muscle atrophy. As a result, this method has become increasingly popular in the rehabilitation of KOA [11].

In recent years, the combination of BFRT with low-intensity training has received widespread attention due to its need for lower exercise adjustments, higher elevation, and less training time.BFRT has been researched for a long time, and some meta-analyses have already investigated this protocol with regard to rehabilitation [12, 13]. However, the current body of research on the effectiveness of BFRT in patients with KOA lacks consensus due to small sample sizes and inconsistent results. Past reviews have primarily examined the impact of BFRT on muscle strength enhancement and clinical outcomes in musculoskeletal diseases. Nevertheless, it is imperative to address the safety concerns associated with BFRT, considering its numerous potential benefits. The main impacts of blood flow restriction on limbs are a decrease in arterial blood inflow and venous blood aggregation, leading to the limb entering a relatively ischemic and hypoxic state, in which metabolic products such as lactate cannot be effectively cleared. Therefore, the safety issues of blood biochemical indicators and adverse events must be considered because the majority of people with KOA are elderly people who may have various complications. Therefore, the goal of this systematic review is to provide a comprehensive overview of the existing data regarding the impact of BFRT on quadriceps strength, muscle size, pain, physical function, biomarkers, quality of life, and adverse events in patients with KOA.

2.1. Protocol Design

For the purpose of conducting the present systematic review, this study adhered to the guiding principle in the Preferred Reporting Item (PRISMA) statement [14], as well as the Cochran Intervention System Review Manual [15]. The protocol for this review has been registered in PROSPERO (ID number: CRD42023439488).

2.2. Data Sources and Search Strategy

Two review raters (Changqing Li and Xiaojiang Zhao) conducted a systematic literature retrieval to identify relevant studies. The following databases were searched: PubMed, Embase, Scopus, Web of Science, and Cochrane Library. There were three sections in the search strings: BFRT, KOA, and RCT. The first section included theme words and free words for BFRT, the second included theme words and free words for KOA, and the third contained theme words and free words for RCTs. In order to ensure that each section contained at least one search term, all theme words and free words were linked with the operator OR, and sections were linked with the operator AND. Additional unpublished records were found by searching the clinical trials registries on ClinicalTrials.gov. Searches were conducted from the database’s inception to June 2023.

2.3. Inclusion and Exclusion Criteria

Based on the PICOS criteria, we identified studies that fulfilled the inclusion criteria. The review allowed comparisons between BFRT and HLRT (≥ 60% 1-RM) or LLRT (< 60% 1-RM), walking, placebo, or another intervention without blood flow restriction [16]. The articles had to be written in English. Review articles, case reports, and observational studies were excluded, as well as studies in which participants had undergone surgery or experienced lower-limb trauma and studies with duplicate data.

2.4. Data Selection and Extraction

Any inconsistencies were addressed through deliberation and, when necessary, with the participation of a third-party evaluator. Two authors (Changqing Li and Xiaojiang Zhao) independently extracted the data from the included studies, encompassing details such as authorship, year of publication, patient demographics, treatment particulars, duration of the intervention, outcomes, and timeframes. When multiple time points were assessed, only the last time point was taken into account. Whenever an article had incomplete data, we contacted the corresponding author via email to request the raw data. The related data were extracted from the included searches, and all extracted variables were revised and checked by Changqing Li and Xiaojiang Zhao for accuracy.

2.5. Assessment of Risk of Bias

The Cochrane Handbook for Systematic Reviews of Interventions [17, 18] was utilized by two independent authors,, Changqing Li and Xiaojiang Zhao. In instances of disagreement, a third researcher, Xue Zhang, was consulted for resolution through discussion.

2.6. Data Analysis

The meta-analysis was conducted using Stata14.0, which was used to enter all the relevant outcome variables. Review Manager 5.3 was used for assessment of the risk of bias. Except for adverse events, the results of other included studies were used as continuous variables, but the testing units and methods were different. Therefore, the standardized mean difference (SMD) or 95% confidence interval (90% CI) were used to calculate continuity data, and the adverse event rate (RR) with 90% CI was calculated for discontinuous data. To examine heterogeneity among the studies, the X² and I² statistics were utilized. A p-value greater than or equal to 0.01 and I² less than 50% indicated that the studies were not heterogeneous, allowing for the application of a fixed-effects model. Conversely, a p-value less than 0.01 and I² greater than or equal to 50% indicated that the studies were heterogeneous. Therefore, a random-effects model was required. Studies were removed one by one to determine heterogeneity. In addition, funnel plots were used to check for research bias, while forest plots were used to describe the analysis results. The significance test level was 0.05.

3.1. Study Selection

A total of 134 records were identified and subsequently screened for their titles and abstracts. Those that did not meet the predetermined criteria were excluded, resulting in the retrieval of 98 published and unpublished records for further assessment. Among these, 41 records were deemed ineligible and therefore not included in the study. The remaining 57 full-text articles were thoroughly evaluated for eligibility, leading to the inclusion of 6 articles in this study. The PRISMA guidelines, specifically designed for reporting systematic reviews, were employed for the article screening process [14], as depicted in Fig. 1.

3.2. Study Characteristics

All studies included in this review were RCTs [19–24] published from 2015 onwards. Three studies were conducted in the USA [22–24], two in Brazil [20, 21], and one in China [19]. Table 1 provides detailed descriptions of the included studies. In total, there were 228 patients, 170 women and 58 men; 102 patients received a BFRT intervention, and 126 received a control group intervention. In studies involving BFRT, all recorded position and pressure, but only four studies reported the size of the cuff [19, 21, 23, 24]. Five outcome indicators of the studies involved changes in muscle and body functions [20–24], while two outcome indicators involved changes in biochemical indicators [19, 22]. In terms of adverse events, four studies reported that patients with KOA were affected by adverse events leading to treatment withdrawal [21–24].

Table 1

Characteristics of included studies.
Reference	Country	Participants Characteristics	Control	Intervention	Cuff Size, Site, Pressure	Outcome Measures, Units	Adverse Effects
Chen et al. [19]	China	18 G1 = 6, G2 = 6, G3 = 6 All women (40–70 years old)	Three resistance exercise tests; the washout period of each test was 72 h. Program performed in either CON group (30% of 1-RM) or RES group (70% of 1-RM), without BFR.	Three resistance exercise tests; the washout period of each test was 72 h. Program performed at 30% of 1-RM with BFR.	12 cm × 124 cm, upper third of the thigh, 70% (AOP).	Perceived exertion: RPE; blood sample: serum IGF-1, GH, blood lactate (BLA), and testosterone.	No patients withdrew.
Bryk et al. [20]	Brazil	34 G1 = 17, G2 = 17 All women (mean 61 years old)	6-week resistance and stretching program, 3 sessions per week. Program performed at 70% of 1-RM, without BFR.	6- week resistance and stretching 7- program, 3 sessions per week. Program performed at 30% of 1-RM with BFR.	Not reported, upper third of thigh; 200 mm Hg.	Pain: NPRS; muscle strength: quadriceps strength; self-report function: Lequesne questionnaire; physical function performance: TUG.	No patients withdrew.
Ferraz et al. [21]	Brazil	48 G1 = 16, G2 = 16, G3 = 16 All women (50–65 years old)	12-week resistance training program, 2 sessions per week. Program performed at either LIRT (30% of 1-RM) or HIRT (80% of 1-RM), without BFR.	12-week resistance training program, 2 sessions per week. Program performed at LIRT (30% of 1-RM) with BFR.	175 mm × 920 mm; inguinal fold; 97.4 ± 7.6 mmHg.	Pain: WOMAC pain subscale; muscle strength: leg press strength, knee extension strength; self-report function: WOMAC; physical function performance: TS, TUG; muscle size: quadriceps (CSA).	4 patients from the HLRT group discontinued during follow-up, exercise-induced knee pain.
Harper et al. [22]	USA	35 G1 = 16, G2 = 19 10 men/women (over 60 years old)	12- week resistance training program, 3 sessions per week. Program 13- performed at MI (60% of 1-RM), without BFR.	12-week resistance training program, 3 sessions per week. Program performed at LI (20% of 1-RM) with BFR.	Not reported, proximal thigh; individualized to each patient.	Pain: WOMAC pain subscale; muscle strength: knee extensor strength; self report function: LLFDI; physical function performance: gait speed, SPPB; biomarkers: serum P3NP, serum TWEAK, serum IGF-1.	14 patients (G1: 3; G2: 11) reported adverse events of knee pain.
Segal et al. [23]	USA	42 G1 = 20, G2 = 22 All men (over 45 years old)	4-week resistance training program, 3 sessions per week. Program performed at LIRT (30% of 1-RM) without BFR.	4-week resistance training program, 3 sessions per week. Program performed at LIRT (30% of 1-RM) with BFR.	65 mm × 650 mm; proximal thigh; 160–200 mm Hg.	Pain: KOOS, muscle strength: isokinetic knee extensor strength, isotonic leg press strength.	One patient withdrew because of intolerance to discomfort from pressure cuff.
Segal et al. [24]	USA	45 G1 = 21, G2 = 24 All women (45–65 years old)	4-week resistance training program, 3 sessions per week. Program performed at LI (30% of 1-RM) without BFR.	4-week resistance training program, 3 sessions per week. Program performed at LI (30% of 1-RM) with BFR.	65 mm × 650 mm; proximal thigh; 160–200 mm Hg.	Pain: (KOOS), strength: isokinetic knee extensor strength, stair climb power; muscle size: quadriceps volume.	One patient withdrew due to intolerance to pain from pneumatic cuff.

3.3. Assessment of Risk of Bias

We adopted the Cochrane bias risk assessment recommended by the Cochrane collaborative group. The evaluation tool was used to evaluate the quality of the included studies. The quality evaluation results are as follows (Fig. 2): ① Random sequence generation: three studies are low risk, while one study cannot be determined as high risk or low risk. ② Allocation concealment: three studies are low risk, while three studies cannot be determined as high risk or low risk. ③ Blinding of participants and personnel: three studies are low risk, and three studies are high risk. ④ Blinding of outcome assessemt: four studies are low risk, and two studies are high risk. ⑤ Incomplete outcome data: all six studies are judged as low risk. ⑥ Selective reporting: all six studies are judged as low risk. ⑦ Other bias: all six studies are judged as low risk.

3.4. Outcome Measures

3.4.1. Strength

Among the six studies, five studies reported 10 examinations of quadriceps muscle strength performance in both the BFRT and control groups [20–24]. In two studies, kilograms were used as the measurement unit, and torque was assessed in three studies. There was no heterogeneity in quadriceps muscle strength between the BFRT group and the control group (I² = 32.4%, p = 0.14).

The muscle strength of the BFRT group was more than that of the control group, and the results of the meta-regression analysis were statistically significant (SMD = 0.39 (95% CI 0.18, 0.60), p = 0.01), as depicted in Fig. 3a.

3.4.2. Muscle Size

Among the six studies, two studies [21, 24] reported three examinations of quadriceps muscle size performance in both the BFRT and control groups. Heterogeneity testing indicated strong heterogeneity in the studies selected for this review (I² = 85.1%, p = 0.00). The quadriceps muscle size of the BFRT group was more than that of the control group, but there was no statistical significance (p > 0.05) (ES = − 0.47, (95% CI − 1.51, 0.58), p = 0.45), as depicted in Fig. 3b.

3.4.3. Pain

Among the six studies, knee joint pain was assessed in the BFRT and control groups six times each [20–24]. After heterogeneity testing, the results showed no heterogeneity among the included studies (I² = 0%, p = 0.85). Based on the fixed-effects model, the BFRT group had less pain than the control group, but this was not statistically significant (SMD = − 0.02 (95% CI − 0.29, 0.25), p = 0.88), as depicted in Fig. 3c.

3.4.4. Physical Function

Among the six studies, a total of four compared and reported the physical function performance of 10 BFRT groups and control groups [20–22, 24]. Among the included trials, heterogeneity was found (I² = 40.5%, p = 0.08), so a random-effects model was used in this meta-analysis.

In terms of physical function the BFRT group had less than the control group, but there was no significant difference (ES − 0.09 (95% CI − 0.37, 0.20), p = 0.14), as depicted in Fig. 3d.

3.4.5. Quality of Life

Among the six studies, two studies reported four examinations of quality of life in two groups with and without BFRT [19, 21]. After heterogeneity testing, the results showed no heterogeneity among the included studies (I² = 38.4%, p = 0.18). The quality of life of the BFRT group was more than that of the control group, and the results of the meta-regression showed no statistical significance (SMD 0.30 (95% CI − 0.13, 0.73), p = 0.30), as depicted in Fig. 4a.

3.4.6. Biomarkers

Among the six studies, two studies reported three examinations of IGF-1 (insulin-like growth factor 1) levels in two groups, with and without BFRT [19, 21]. After heterogeneity testing, the results showed no heterogeneity among the included studies (I² = 47.1%, p = 0.15). the IGF-1 of the BFRT groupwas more than the control group, and, according to the results of the meta-regression, this was statistically significant (SMD 1.31 (95% CI 0.73, 1.89), p = 0.00), as depicted in Fig. 4b.

3.4.7. Adverse Events

Among the six studies, four studies reported eight adverse events [21–24]. Heterogeneity testing indicated no heterogeneity among the articles selected for this study (I² = 32.3%, p = 0.21). Adverse events in the experimental group were more than in the control group, but, according to the results of the meta-regression, this was not statistically significant (RR 0.45 (95% CI 0.20, 1.01), p = 0.05), as depicted in Fig. 4c.

3.5. Sensitivity Analysis

In order to assess the overall impact of each study, a sensitivity analysis was conducted by excluding individual studies. The analysis revealed that the study by Segal et al. [24] was the primary cause of heterogeneity for physical function performance (I² = 40.5%, p = 0.08 versus I² = 0%, p = 0.53). But deleting this study did not change the significane of the pooled results (p = 0.57 vs. p = 0.14). For quadriceps muscle size performance, the analysis showed that the Segal et al. [24] study contributed the most to the heterogeneity of the pooled data (I² = 85.1%, p = 0.00 vs. I² = 0.5%, p = 0.31). But deleting this study did not change the significane of the pooled results (p = 0.47 vs. p = 0.45). For the other results, the sensitivity analyses showed relatively robust results for heterogeneity and statistical significance.

3.6. Analysis of Publication Bias

This study employed the funnel plot technique to examine the presence of publication bias. The dispersion points of the funnel plot, which represent the outcome indicators analyzed in this study, exhibited a predominantly symmetrical pattern. Furthermore, a deviation test was conducted and indicated that all p-values exceeded the threshold of 0.05, suggesting the absence of publication bias, as depicted in Figs. 5 and 6.

The purpose of this study was to analyze the effect of BFRT on KOA. In treating patients with KOA, we found that BFRT was superior in improving muscle strength and biomarkers, with statistically significant differences, but not in improving other symptoms, including those related to muscle size, pain, physical function, quality of life, and adverse events, with statistically insignificant differences. Maintaining and increasing muscle mass and strength are important foundations for ensuring the quality of daily life, and improving muscle strength and quality is considered the greatest benefit achieved through BFRT [25, 26]. Out of the seven studies that examined this aspect, four reported improvements in strength. Patients with KOA commonly face issues of muscle weakness and atrophy. Our review indicates that individuals with KOA frequently experience pain and a gradual decline in their ability to perform activities of daily living [27, 28]. There exists a substantial body of evidence indicating a consistent association between muscle atrophy, physical decline, joint degeneration, and increased pain with diminished muscle strength in individuals diagnosed with KOA [29]. Therefore, the strength of the quadriceps femoris is crucial for achieving good knee joint stability and maintaining function. In our review, five out of six studies evaluated this variable [20–24], and three studies showed a marked improvement in quadriceps muscle strength in the BFRT group compared to in the control group. One of the studies also suggested that the effect of BFRT on quadriceps femoris hypertrophy is similar to that of HLRT [21]. However, two studies did not find a marked improvement compared with the control group. These findings align with those of previous meta-analyses involving older individuals [30, 31].

Pain is the most concerning issue for KOA patients, and its baseline levels are related to the prognosis of knee OA [32]. Among the five studies [20–24] investigating this variable, two studies showed a marked increase in knee pain [21, 23], and three studies showed no marked improvement in knee pain [20, 22, 24]. In the studies evaluating patients with KOA, there was a marked improvement in knee pain during training with BFRT and at the conclusion of treatment, as opposed to in high-intensity strength training. In [21], it was found that both the BFRT group and the low-intensity exercise control group experienced significant reductions in pain scores. However, 25% of the control group suffered from exercise-related pain and dropped out of the study. In [20], improvements in terms of pain across both groups were found, but the BFR group had better results than the high-load control group. Patients with KOA may benefit from training with low loads and low pain to adhere to exercise. In contrast, the other three studies [20, 22, 24] also included patients with symptomatic knee osteoarthritis, and no significant results were found. Although pain and physical function often occur simultaneously in KOA, doctors often pay more attention to pain. For patients with KOA, physical function is equally important [33]. In addition to physical functions, we also focused on the quality of life, but our summary results indicate that there was no significant improvement in the BFRT group as opposed to the control group. This is consistent with previous meta-analysis results [30].

A prior study showed that BFR training enhances the secretion of hormones associated with muscle growth in individuals who are in good health [34]. IGF-1 participates actively in cell growth. However, the physiological mechanism of the impact of resistance exercise on IGF-1 is still unclear. This review investigated this variable in two studies [19, 20]. According to one of the studies, the control group exhibited significantly lower levels of IGF-1 than the BFRT and RES groups, both post-exercise and 15 min after exercise [19], whereas the other study showed no significant improvement in IGF-1 between the BFRT group and the control group [20], which is similar to a previous study [35]. Due to the limited number of studies, we were unable to investigate the impact of BFRT on IGF-1. Therefore, it is recommended that future BFR clinical studies evaluate baseline, stem, and IGF-1 at prognostic and follow-up time points. These discoveries will offer a theoretical foundation, aiding researchers and physical therapists in formulating a more evidence-based exercise plan.

KOA mainly occurs in elderly people, who frequently experience complications, such as syndromes associated with metabolism. Therefore, adverse events are an important issue. Previous studies have suggested that musculoskeletal disorders and knee OA do not pose a significant risk with BFRT [36]. The results of this research indicate that there was no statistically significant difference in the occurrence of adverse events between the group that underwent BFRT and the control group (RR 0.45 (95% CI 0.20, 1.01), p = 0.05, I² = 0%). These findings suggest that the number of adverse events experienced by individuals in the BFRT group was comparable to that experienced by individuals in the resistance training group. Furthermore, our findings align with previous research findings [30] that also reported no significant difference in adverse events between these two groups.

One advantage of this review is that all the studies included are RCTs with moderate sample sizes. However, this study has the following limitations: Due to BFRT having only recently been introduced and applied to the field of sports rehabilitation, there is a limited amount of research on its effects, resulting in the results of only six trials being pooled and a relatively small sample size. In general, when the trial size is too small to test the effect of treatment, it is appropriate to describe the result as inconclusive rather than negative. One of the studies included in this meta-analysis [19] had only six participants in each group, which may have affected the final results. In three of the included studies [20–22], exercise intensity was higher in the control group than in the BFRT group. All trials had follow-up time points of 12 weeks or less. One study included in this meta-analysis only conducted three resistance exercise tests, one with a washout period of 72 hours. Therefore, without evaluating BFRT for KOA in the mid (6–12 months) to long term (≥ 12 months), the effects are impossible to determine. The results of the pooled analyses may also be influenced by factors such as the total number of weeks of BFRT practice, the number of times each exercise was carried out, and the duration of each exercise, so future studies should focus more on developing a detailed training regimen for patients with KOA. It is worth noting that this review solely encompassed publications written in English, which could lead to potential studies not being included.

In conclusion, the evidence reviewed suggests that BFRT may be more beneficial for muscle strength and biomarkers than control training but that it may not be more effective in treating other symptoms of patients with KOA, including those related to muscle size, pain, physical function, quality of life, and adverse events. It is imperative that further research is conducted to evaluate the mid- and long-term effects of BFRT for patients with KOA, as well as the adverse events that may occur. Additionally, studies should investigate the effectiveness of combining low-intensity resistance training with BFRT and resistance training with low-intensity BFRT.

BFRT

blood flow restriction trainingon

KOA

knee osteoarthritis

RCTs

randomized controlled trials

LLRT

low-load resistance training

high-load resistance training

low-load resistance training

CON group

RES group

Ethics Approval and Consent to Participate: Not cpplicable

Consent for Publication: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Availability of Data and Materials: Not applicable

Competing Interests: The authors declare that they have no competing interests.”

Funding: This work was supported by the Quality Engineering Project of the Higher Education Institutions of Anhui Province (2022jyxm987), the Natural Science Foundation of the Higher Education Institutions of Anhui Province (2022AH051434), and the National-Level Innovation Training Program for College Students (202310367042).

Author Contributions: For research articles with several authors, the following statements should be used “Conceptualization, Li, C.−Q. and Zhao, X.−J.; methodology, Li, C.−Q.; software, Zhao, X.−J.; validation, Li, C.−Q.;Wen,H.−B; Zhang, X.; Ma, C. and Zhao, X.−J.; formal analysis,Li, C.−Q.; investigation, Zhao, X.−J.; resources, Li, C.−Q. and Zhao, X.−J.; data curation, Li, C.−Q. and Zhao, X.−J.; writing—original draft preparation, Li, C.−Q. and Zhao, X.−J.; writing—review and editing, Li, C.−Q. and Zhao, X.−J.; visualization, Li, C.−Q.; supervision, Zhao, X.−J.; project administration,Zhao, X.−J.; funding acquisition, Zhao, X.−J. All authors have read and agreed to the published version of the manuscript.”

Acknowledgements: The authors thank Huang Tao of the School of Physical Education and Sport, Huanggang Normal University, for assisting with the statistical analysis.

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No competing interests reported.

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Effects of blood flow restriction training in patients with knee osteoarthritis: A meta- analysis

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Abstract

Figures

1. Background

2. Methods

2.1. Protocol Design

2.2. Data Sources and Search Strategy

2.3. Inclusion and Exclusion Criteria

2.4. Data Selection and Extraction

2.5. Assessment of Risk of Bias

2.6. Data Analysis

3. Results

3.1. Study Selection

3.2. Study Characteristics

3.3. Assessment of Risk of Bias

3.4. Outcome Measures

3.4.1. Strength

3.4.2. Muscle Size

3.4.3. Pain

3.4.4. Physical Function

3.4.5. Quality of Life

3.4.6. Biomarkers

3.4.7. Adverse Events

3.5. Sensitivity Analysis

3.6. Analysis of Publication Bias

4. Discussion

5. Advantages and Limitations of this Study

6. Conclusions

Abbreviations

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