Effect of Low-Intensity Bloodflow Restriction Training on Nontraumatic Knee Joint Conditions: A Systematic Review and Meta-analysis

Abstract

Context:

Nontraumatic knee conditions are common in clinical practice. Existing pharmaceutical and immobilization approaches provide limited pain relief and functional enhancement. Low-intensity bloodflow restriction training (LI-BFRT) is being investigated as a nonpharmacological alternative; however, its efficacy is uncertain.

Objective:

To assess the effectiveness of LI-BFRT for nontraumatic knee conditions and compare it with high-intensity resistance training (HI-RT) and low-intensity resistance training (LI-RT).

Data Sources:

PubMed, EBSCO, Science Direct, Cochrane Library, China Knowledge Infrastructure, Wanfang Data, and VIP databases were searched until May 30, 2023.

Study Selection:

Original randomized controlled trials involving nontraumatic knee joint conditions with interventions consisting mainly of LI-BFRT, HI-RT, or LI-RT. The results assessed mainly pain and muscle performance.

Study Design:

Systematic review and meta-analysis.

Level of Evidence:

Level 1.

Data Extraction:

Sample characteristics, study design, country, disease, groups, evaluation time, duration, and outcomes were extracted.

Results:

A total of 13 randomized controlled trials were included in the systematic review. Compared with pretreatment, LI-BFRT significantly alleviated pain (weighted standardized mean difference [SMD], -1.33; 95% CI, -1.62 to -1.05), with better additional effects on hip muscle training (SMD, -3.14; 95% CI, -4.07 to -2.75). Compared with LI-RT, LI-BFRT significantly relieved pain in male patients (SMD, -1.47; 95% CI, -1.92 to -1.01). LI-BFRT significantly increased quadriceps cross-sectional area (SMD, 0.53; 95% CI, 0.27-0.78), knee extension strength (SMD, 0.84; 95% CI, 0.48-1.2), and leg press strength (SMD, 0.64; 95% CI, 0.34-0.94) compared with pretreatment. Its effects were superior to those of LI-RT and similar to those of HI-RT. However, sex differences in muscle strength improvement were observed.

Conclusion:

In patients with nontraumatic knee joint conditions, LI-BFRT effectively alleviated pain, increased muscle cross-sectional area, and enhanced muscle strength. LI-BFRT showed pain relief comparable with that of LI-RT while surpassing LI-RT in muscle growth and strength improvement.

Amid growing health consciousness and a surge in sports participation, the number of nontraumatic bone and joint conditions has increased. ⁴³ Nontraumatic knee joint conditions refer primarily to diseases such as rheumatoid arthritis and osteoarthritis, as well as long-term overuse, poor posture, muscle imbalances, etc, and manifest as long-term chronic joint inflammation and synovial swelling, leading to synovitis. The chronic inflammatory environment in the joint leads to synovial expansion, known as “pannus,” which invades the bones surrounding the cartilage-bone junction, resulting in bone erosion and cartilage degeneration, causing continued damage to the knee joint.^32,38,50 The knee joint, often afflicted, exhibits symptoms of pain, deformity, and diminished muscle strength.^33,51

Although nontraumatic conditions require no surgical treatment, they have gained increasing attention in the rehabilitation field as they may result in lasting functional limitations and reduced quality of life.^25,27 Exercise therapy has unique advantages for pain alleviation and muscle strength enhancement. The American College of Sports Medicine recommends utilizing a ≥70% 1-repetition maximum (1-RM) load for training to improve muscle strength. ¹ However, patients with nontraumatic knee joint conditions may not tolerate the pain associated with high-intensity resistance training (HI-RT), and such training could increase the risk of secondary injuries. ⁵⁵

Introduced by Sato in 2005, ⁴⁶ bloodflow restriction (BFR) training (BFRT) applies pressure using bands to restrict bloodflow, ⁷ promotes metabolic stress, increases tension, and induces muscle hypertrophy in anaerobic environments.^2,11 Research suggests that low-intensity bloodflow restriction training (LI-BFRT) produces results comparable with those of HI-RT, with minimal side effects such as muscle damage, subcutaneous bleeding, or numbness.^13,52 Owing to its distinctive therapeutic features, BFR technology is used widely in the rehabilitation of musculoskeletal joint disorders, including knee injuries.^5,41 However, the therapeutic efficacy of BFR technology in treating knee joint pain and functionality remains controversial owing to variations in injury types, patient selection, and exercise protocols.

The purpose of this systematic review and meta-analysis was to (1) determine the effectiveness of LI-BFRT in treating nontraumatic knee joint conditions and (2) compare the efficacy of LI-BFRT with LI-RT and HI-RT for nontraumatic knee joint conditions.

Methods

This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. ⁴⁰

Search Strategy

Following the PICO framework, ²³ we performed an initial search in electronic databases (PubMed, EBSCO, Science Direct, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and VIP Database) to identify randomized controlled trials (RCTs) exploring the effectiveness of LI-BFRT in treating nontraumatic knee joint conditions and pain. The search covered the inception of databases until May 30, 2023, without language restrictions.

We utilized the following search terms in combination: BFRT, bloodflow restriction training, KAATSU, occlusion, pressure, compression, regional blood, knee injury, knee dislocation, knee osteoarthritis *, leg degenerative arthritis *, rheumatoid arthritis *, rheumatoid arthritis, leg pain, and patellar pain.

Eligibility Criteria

The inclusion criteria were as follows: (1) RCTs; (2) patients with nontraumatic knee joint conditions; (3) LI-BFRT as the primary intervention; (4) a control group receiving low-intensity resistance training (LI-RT) or HI-RT; and (5) results reporting pain and muscle-related outcomes.

The exclusion criteria were as follows: (1) involving invasive treatment; (2) unquantifiable research outcomes; (3) full-text unavailable through various channels; and (4) duplicate literature.

Data Extraction

Two independent reviewers extracted the following sample characteristics: study design, country, disease, groups, evaluation time, and duration. The outcomes extracted included pain scores, quadriceps cross-sectional area (QCSA), knee extension strength (KES), and leg press strength (LPS).

Risk of Bias

Two reviewers independently assessed potential bias using an improved Cochrane risk of bias tool in 5 domains of bias (randomization, intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result) as high, some concern, or low risk of bias. ⁴⁹ The reviewers resolved any discrepancies by consensus.

Level of Evidence

Grading of Recommendations Assessment, Development, and Evaluation Rating of Evidence Quality

The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system categorizes evidence quality based on 5 factors^17-21: bias risk, inconsistency, imprecision, indirectness, and publication bias. The evidence quality was classified as high, moderate, low, or very low. The recommendation levels were divided into strong and weak.

Oxford Centre for Evidence-Based Medicine: Levels of Evidence

Evidence levels were determined based on the latest Oxford Centre for Evidence-Based Medicine charts. ³⁹

Statistical Analyses

Statistical analyses were performed using STATA 15.1 (STATA Corp). Hedge’s g and 95% CI served as effect size measures for continuous data. A random-effects model and standardized mean difference (SMD) were used. Heterogeneity was assessed using the χ² test and I² statistic. Homogeneity was indicated if P > 0.1 and I² < 50%, whereas significant heterogeneity was considered if P < 0.1 and I² > 50%. Subgroup and sensitivity analyses were performed to explore the sources of heterogeneity.

Results

Search Result

The initial search found 4383 relevant studies from 8 databases. Of these, 683 duplicates were excluded from the analysis. After title and abstract reviews, 43 articles remained for further evaluation. A total of 30 articles did not meet the inclusion criteria and were excluded from the study. Finally, 13 studies were included in the meta-analysis (Figure 1).^{4,8,15,16,22,29,30,31,33,44,47,48,51}

Figure 1.

PRISMA flowchart of the literature search. BFR, bloodflow restriction; RCT, randomized controlled trial.

Study Characteristics

A total of 13 RCTs (from years 2015 to 2022) comprising 609 participants were included (dropout rate, 56; completion rate, 553 [90.8%]). LI-BFRT, LI-RT, and HI-RT were evaluated in 257, 149, and 147 patients, respectively. Patients in the LI-BFRT, LI-RT, and HI-RT groups received 20% to 30%, 20% to 30%, and 50% to 80% of 1-RM resistance training, respectively. These studies included various nontraumatic knee joint conditions (osteoarthritis, rheumatoid arthritis, and patellofemoral pain). The intervention period was 4 to 12 weeks or longer (Table 1).

Table 1.

Details of the included studies

Study ID	Design	Country	Disease	Final Sample Size		Methods				Outcomes
				(I/C1/C2)	(M/W)	Intervention Group	Control Group	Evaluation Time	Frequency
Ferraz 2018 15	RCT	Brazil	OA	34(12/12/10)	(N/Y)	LI-BFRT (20% to 30% 1-RM, 70% LOP-97.4 ± 7.6 mmHg)	C1:LI-RT(20% to 30% 1-RM) C2:HI-RT 50% to 80% 1-RM)	12 weeks	2 sessions/week	LPS, KES, QCSA, WOMAC
Harper 2019 22	RCT	USA	OA	35 (16/19/N)	(Y/Y)	LI-BFRT (20% 1-RM, 0.5 (SBP) + 2 (thigh circumference) + 5mmHg)	C2:MI-RT (60% 1-RM)	3, 6, 9,12 weeks	3 sessions/week	LPS, KES, WOMAC
Segal 2015 48	RCT	USA	OA	40 (19/21/N)	(N/Y)	LI-BFRT (30% 1-RM,160–200 mmHg)	C1:LI-RT (30% 1-RM)	4 weeks	3 sessions/week	LPS, KES, QCSA, KOOS, NPRS
Segal 2015 47	RCT	USA	OA	41 (19/22/N)	(Y/N)	LI-BFRT (30% 1-RM, 160–200 mmHg)	C1:LI-RT (30% 1-RM)	4 weeks	3 sessions/week	LPS, KES, KOOS, NPRS
Li 2022 33	RCT	China	OA	48 (25/23/N)	(Y/Y)	Regular training + LI-BFRT (30% 1-RM, 60% LOP-90.56 mmHg)	C1:Regular training	6 weeks	3 sessions/week	QCSA, WOMAC
Bryk 2017 4	RCT	Brazil	OA	34 (17/17/N)	(Y/Y)	LI-BFRT (30% 1-RM, 200 mmHg),	C2:HI-RT (70% 1-RM)	6 weeks	3 sessions/week	KES, KOOS, NPRS
Rodrigues 2020 44	RCT	Brazil	RA	45 (15/15/15)	(N/Y)	LI-BFRT (20% to 30% 1-RM, 70% LOP-108.92 ± 14.63 mmHg)	C2:HI-RT (50% to 70% 1-RM) C1:Blank control	12 weeks	2 sessions/week	LPS, KES, QCSA, VAS
Jønsson 2021 29	RCT	Austria	RA	17 (9/8/N)	(N/Y)	LI-BFRT (20% to 30% 1-RM, 50% LOP)	C1:LI-RT (20% to 30% 1-RM)	4 weeks	3 sessions/week	LPS, KES, VAS
Li 2021 30	RCT	China	RA	60 (30/30/N)	(Y/Y)	Regular training + LI-BFRT (30% 1-RM, 70% LOP-105.07 ± 13.72 mmHg)	C1:Regular training	6, 12 weeks	3 sessions/week	VAS
Li 2020 31	RCT	China	PFP	54 (18/18/18)	(Y/Y)	Regular training + LI-BFRT (30% 1-RM, 70% LOP)	C2:HI-RT (70% 1-RM) C1:Blank control	4, 8 weeks	3 sessions/week	KES, QCSA, VAS
Wang 2020 51	RCT	China	PFP	26 (13/13/N)	(Y/Y)	LI-BFRT (30% 1-RM, 50% LOP)	C1:HI-RT (70% 1-RM)	6 weeks	2 sessions/week	VAS
Giles 2017 16	RCT	America	PFP	69 (34/35/N)	(Y/Y)	LI-BFRT (30% 1-RM, 60% LOP)	C1:HI-RT (70% 1-RM)	8 weeks	3 sessions/week	KES, QCSA, VAS
Constantinou 2022 8	RCT	Cyprus	PFP	60 (30/30/N)	(Y/Y)	LI-BFRT (30% 1-RM, 70% LOP)	C2:HI-RT (70% 1-RM)	4 weeks	3 sessions/week	VAS

C1, control group 1 (LI-RT); C2, control group 2 (HI-RT); HI-RT, high-intensity resistance training; I, intervention group; ID, identification; KES, knee extension strength; KOOS, Knee Osteoarthritis Outcome pain Score; LI-BFRT, low-intensity training with bloodflow restriction; LI-RT, low-intensity resistance training; LOP, limb occlusion pressure; LPS, leg press strength; M, men; N, no; NPRS, numerical pain rating scale; OA, osteoarthritis; PFP, patellofemoral pain; QCSA, quadriceps cross-sectional area; RA, rheumatoid arthritis; RCT, randomized controlled trial; SBP, systolic blood pressure; VAS, visual analog scale; W, women; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index pain score; Y, yes.

Risk of Bias in the Included Studies

The assessment of the risk of bias in the included studies indicated that, of the 13 RCTs, 9 were considered to have a low risk of bias, while the remaining 4 had some concerns (Figure 2, Appendix Table A1, available in the online version of this article).

Figure 2.

Risk of bias summary.

Outcomes

Knee Pain

Visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to assess pain, with lower scores indicating less pain. In the random effects model, LI-BFRT significantly reduced pain compared with the baseline (SMD, -1.78; 95% CI, -2.38 to -1.17; P = 0.00), but with high heterogeneity (I² = 80.2%). The analysis revealed that additional hip muscle training resulted in high heterogeneity. The subgroup analysis showed reduced heterogeneity (I² = 0.0%, for normal and additional hip training) (Figure 3).

Figure 3.

Effect of LI-BFRT on pain. LI-BFRT, low-intensity bloodflow restriction training; SMD, standardized mean difference.

LI-BFRT significantly reduced pain compared with LI-RT (SMD, -0.83; 95% CI, -1.49 to -0.17; P = 0.00), but with high heterogeneity (I² = 81.1%). Sex was the primary source of heterogeneity (female vs male patients, P = 0.00). Subgroup analysis according to sex revealed reduced heterogeneity (I² = 0.0%, I² = 35.4%, respectively) (Figure 4, Table 2).

Figure 4.

Differences between LI-BFRT, LI-RT, and HI-RT in alleviating knee pain. HI-RT, high-intensity restriction training; LI-BFRT, low-intensity bloodflow restriction training; LI-RT, low-intensity restriction training; SMD, standardized mean difference.

Table 2.

Effect of sex on pain relief with LI-BFRT (regression analysis) ^a

	Coefficient	SE	z	P>|z|	95% CI
Female	1.385456	0.3132008	4.42	0.00	0.7715941	1.999319
Control	-0.463306	0.2014993	-7.26	0.00	-1.858237	-1.068374

LI-BFRT, low-intensity bloodflow restriction training; SE, standard error.

^aSuccessive values of tau² differ by less than 10^-4: convergence achieved.

LI-BFRT significantly reduced pain compared with HI-RT (SMD, -0.49; 95% CI, -0.75 to -0.23; P = 0.80), with low heterogeneity (I² = 0.0%) (Figure 4).

Quadriceps Cross-Sectional Area

Using ultrasound to assess the QCSA, higher scores indicated greater QCSA. In the random-effects model, LI-BFRT demonstrated a significant increase in QCSA compared with baseline (SMD, 0.53; 95% CI, 0.27-0.78; P = 0.46), with minimal heterogeneity (I² = 0.0%) (Appendix Figure A1)

LI-BFRT significantly increased QCSA compared with LI-RT (SMD, 1.78; 95% CI, 1.42-2.41; P = 0.41), with low heterogeneity (I² = 0.0%). However, no significant difference in the QCSA between patients of the LI-BFRT and HI-RT groups was observed (SMD, -0.00; 95% CI, -0.32 to 0.32; P = 0.64), and a low heterogeneity was found (I² = 0.0%) (Figure 5).

Figure 5.

Differences between LI-BFRT, LI-RT, and HI-RT in increasing QCSA. HI-RT, high-intensity resistance training; LI-BFRT, low-intensity training with bloodflow restriction; LI-RT, low-intensity resistance training; QCSA, quadriceps cross-sectional area; SMD, standardized mean difference.

Strength

During knee extension, weightbearing reflects muscle strength, with higher scores indicating greater muscle strength. In the random-effects model, LI-BFRT significantly increased KES compared with baseline (SMD, 0.84; 95% CI, 0.48-1.2; P = 0.07), with moderate heterogeneity (I² = 48.7%) (Appendix Figure A2).

LI-BFRT significantly increased KES compared with LI-RT, but had high heterogeneity (SMD, 0.62; 95% CI, 0.17-1.07; I² = 64.8%; P = 0.01) (Appendix Figure A3). Sensitivity analyses were conducted for each study, revealing that the study by Segal et al ⁴⁶ was the main source of heterogeneity (Appendix Figure A4). After excluding that study, heterogeneity decreased (SMD, 0.8; 95% CI, 0.52-1.08; I² = 0.0%; P = 0.90). Moreover, all the participants in the study by Segal et al ⁴⁶ were male. Finally, LI-BFRT showed similar effects to HI-RT in increasing KES (SMD, -0.21; 95% CI, -0.47 to -0.06; P = 0.56) with low heterogeneity (I² = 0.0%) (Figure 6).

Figure 6.

Differences between LI-BFRT, LI-RT, and HI-RT in increasing KES. HI-RT, high-intensity resistance training; KES, knee extension strength; LI-BFRT, low-intensity training with bloodflow restriction; LI-RT, low-intensity resistance training; SMD, standardized mean difference.

Weight borne during the leg press reflects the corresponding muscle strength, with higher scores indicating greater LPS. In the random-effects model, LI-BFRT significantly increased LPS compared with baseline (SMD, 0.64; 95% CI, 0.34-0.94; P = 0.62), with low heterogeneity (I² = 0.0%) (Appendix Figure A5).

LI-BFRT showed similar effects to LI-RT (SMD, 0.43; 95% CI, -0.03 to 0.89; P = 0.11) with moderate heterogeneity (I² = 47.6%) (Appendix Figure A6). After excluding the study by Segal et al, ⁴⁷ heterogeneity significantly decreased. Finally, LI-BFRT had similar effects to HI-RT in increasing LPS levels (SMD, -0.26; 95% CI, -0.68 to 0.17; P = 0.81), with low heterogeneity (I² = 0.0%) (Figure 7).

Figure 7.

Differences between LI-BFRT, LI-RT, and HI-RT in increasing LPS. HI-RT, high-intensity resistance training; LI-BFRT, low-intensity training with bloodflow restriction; LI-RT, low-intensity resistance training; LPS, leg press strength; SMD, standardized mean difference.

Level of Evidence

GRADE System Recommendation Evaluation

Based on the quality assessment and meta-analysis, the GRADE system was used to evaluate the findings. The results indicated that approximately 50% of the evidence was of high quality, while the remaining 50% was of moderate quality (Appendix Table A2).

Oxford Centre for Evidence-Based Medicine Evaluation of the Level of Evidence

The commonness of the problem was at Level 2, whereas the evaluation of diagnosis, prognosis, treatment benefits, treatment harms, and screening was at Level 1 (Appendix Table A3).

Discussion

Necessity of Research

Nontraumatic conditions of the knee joint, such as osteoarthritis and rheumatoid arthritis, can cause mobility and sensory (pain) impairments. Currently, these conditions can be relieved only through medication or immobilization to alleviate pain, and only a few rehabilitative methods are available to improve mobility and sensory impairments. ⁵⁵

BFRT is beneficial for musculoskeletal injuries and is used primarily in sports. It aids in strength recovery, prevents muscle atrophy, improves aerobic performance, and enhances overall clinical outcomes. ⁹ Currently, training is provided primarily to young and middle-aged persons with acute traumatic injuries, ⁵⁴ older persons with chronic degenerative changes, ²⁴ and those with anterior cruciate ligament injuries.^3,53 Analyses have focused mainly on age, ³⁵ parts of the body, ⁵⁵ and improvements in healthy populations.^6,10

Studies have reported the effectiveness and role of LI-BFRT in nontraumatic knee joint conditions ³⁸ ; however, owing to geographical and temporal variations, further analysis is needed to evaluate the efficacy of LI-BFRT for nontraumatic knee joint conditions.

This article presents a comprehensive evaluation of the effectiveness of LI-BFRT in nontraumatic knee joint conditions and compares its efficacy with that of LI-RT and HI-RT. This further promotes the application of LI-BFRT in rehabilitation.

Main Findings

First, this study found that LI-BFRT significantly reduced pain. Most studies have suggested that BFRT can alleviate musculoskeletal pain by encouraging the release of pain-inhibiting substances such as nitric oxide, catecholamines, and opioid peptides under hypoxic conditions,^14,28 or another theory is that high-tension elastic bands induce moderate ectopic pain, triggering diffuse injury inhibition, and causing endogenous pain. ⁴² This is because ascending injury signals in the distal body can inhibit the nociceptive response of the spinal cord and trigeminal nucleus caudalis neurons. ¹² Such conditioning stimulation exerts a descending analgesic effect on the sensory perception of existing injuries in the body. ⁴⁵

The findings of this study are consistent with the aforementioned theories; however, high heterogeneity was observed. Further analysis revealed that 2 articles included additional hip joint training with higher loads, and subgroup analysis showed a significant reduction in heterogeneity. Therefore, additional hip muscle training may contribute to alleviating knee joint pain; however, further research is needed to validate this hypothesis.

Furthermore, this study found that, compared with LI-RT, LI-BFRT significantly reduced pain scores in male patients, although the effect was not as prominent in female patients. This finding indicates that sex significantly influences pain perception. In the field of pain biology, sex differences are observed at various levels, including the genetic, molecular, cellular, systemic, and socio-behavioral levels. ³⁴ For example, sex hormones have been implicated in differences in pain perception. ³⁶ Anatomic and physiological sex differences in neural pathways associated with pain modulation also occur. ²⁶ Therefore, this study speculates that the differential effects observed in male and female patients may be attributed to differences in hormone levels during the training process or variations in the pathways of pain-inhibiting substances. However, further investigation is required. In addition, the inability of female patients to tolerate high-intensity load training may also contribute to differences in treatment outcomes.

Research has shown that for every 340-unit increase in quadriceps strength, there is an approximate 0.05-point reduction in knee joint pain. ³⁷ In terms of increasing QCSA, the effect of LI-BFRT was superior to that of LI-RT and similar to that of HI-RT. Although the disease types were different, the conclusions of this study are similar to those of a meta-analysis of therapeutic exercises for traumatic knee joint conditions. ⁵³ This result can be explained by the following theory: BFRT can induce the synthesis of metabolic hormones, strengthen the muscle protein synthesis signaling pathway, facilitate the rapid recruitment of muscle fibers, and induce a cellular swelling response through the muscle tissue ischemia and hypoxia pathways. ³⁷

To prevent muscle atrophy and increase muscle strength, HI-RT is usually recommended. However, HI-RT is hard to perform in patients with knee joint injuries. Furthermore, HI-RT may harm the knee joint and cause severe pain. ⁵⁵ This study provides evidence for the use of LI-BFRT as an alternative to HI-RT in these patients.

In addition, this study included indicators such as the KES and LPS, which have not been the focus of previous studies. Both KES and LPS can serve as indicators of different aspects of the muscle strength response.

Regarding KES, after excluding high-sensitivity articles, the effectiveness of LI-BFRT was superior to that of LI-RT and similar to that of HI-RT. This result is consistent with the QCSA analysis. The quadriceps is involved in maintaining body posture, extending the calf, and flexing the knee joints. Therefore, we speculate that an increase in quadriceps muscle size may play a positive role in increasing KES; however, further research is needed to establish the correlation between the 2.

Regarding LPS, the results indicated that the effectiveness of LI-BFRT was similar to that of LI-RT and HI-RT. After excluding the same article (including only male patients), the results for the LPS were similar to those for the KES, showing a significant reduction in heterogeneity. Therefore, we speculate that these 2 indicators are correlated positively with an increase in quadriceps muscle size. Because the excluded studies included only male participants, we suggest that sex may have an important influence on KES and LPS.

Advantages and Limitations

This systematic review and meta-analysis had the following advantages: (1) analyzing LI-BFRT efficacy from various angles (horizontal and vertical perspectives); (2) broad representativeness of patients; (3) evaluation of KES and LPS, which are less studied indicators, thus presenting new insights and evidence for rehabilitating disease-induced movements and sensory impairment; and (4) blinded evaluations and objective measures in the majority of studies, reducing evaluator bias.

This analysis also had some limitations: (1) limited articles per subgroup restrict the reliability of the meta-analysis on the considerable impact of sex. Further clinical studies are required to address these biases. (2) Incomplete randomization or allocation concealment of some articles was another limitation of this study. (3) Inconsistent data quality: whereas most studies employed more rigorous methods, there were some with less stringent approaches.

Conclusion

LI-BFRT effectively relieved pain and enhanced muscle size and strength in patients with nontraumatic knee joint conditions. It is similar to LI-RT in pain relief, but surpasses LI-RT in increasing muscle size and strength, comparable with HI-RT.