https://orcid.org/0000-0003-1039-7550
Figures
Abstract
Introduction
The aims of this review was to investigate the effectiveness of closed kinetic chain exercise (CKCE) on pain, function, and proprioception in individuals with knee osteoarthritis (OA).
Methods
Nine databases were searched up to December 2023. Randomized controlled trials (RCTs) examining the effects of CKCE in individuals with knee OA were included. The methodological quality was assessed using the PEDro scale, and the level of evidence was evaluated with the GRADE system. A random-effects meta-analysis was conducted to assess differences between treatment groups for the primary outcomes (pain and function). Effect sizes were calculated using standardized mean differences (SMDs) with 95% confidence intervals (CIs).
Results
A total of 24 studies were included in the descriptive analysis, and 18 studies were included in the quantitative analysis (meta-analysis). The meta-analysis results indicated that CKCE treatment led to greater improvements in pain (SMD = −0.76; 95% CI: −1.51, −0.01) and function (SMD = −1.25; 95% CI: −1.88, −0.62) compared to no treatment. A subgroup meta-analysis showed that the combined treatment of CKCE and conventional physical therapy (CPT) resulted in greater improvements in pain (SMD = −1.18; 95% CI: −1.70, −0.67) and function (SMD = −1.27; 95% CI: −1.79, −0.75) compared to CPT alone. The risk of bias assessment revealed that two studies were of low quality, nine were of fair quality, and the remaining 13 were of high quality. The GRADE system indicated a low quality of evidence for the effects of CKCE on both pain and function.
Citation: Fadil A, Muaidi QI, Alayat MS, AlMatrafi NA, Subahi MS, Alshehri MA (2025) The Effectiveness of closed kinetic chain exercises in individuals with knee osteoarthritis: A systematic review and meta-analysis. PLoS One 20(5): e0322475. https://doi.org/10.1371/journal.pone.0322475
Editor: Ateya Megahed Ibrahim El-eglany, Prince Sattam bin Abdulaziz University, SAUDI ARABIA
Received: October 1, 2024; Accepted: March 23, 2025; Published: May 2, 2025
Copyright: © 2025 Fadil et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: “All relevant data are within the paper and its Supporting Information files.”
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
1. Introduction
Osteoarthritis (OA) is a disease that affects the entire joint structure, causing progressive damage to the articular cartilage in synovial joints, along with subchondral bone sclerosis, osteophyte formation, and mild persistent synovial inflammation [1]. In 1986, the American Rheumatism Association defined OA as “a group of overlapping disorders with different etiologies but similar biological, morphological, and clinical outcomes.” The prevalence of knee OA in the United States has recently increased due to rising body mass index and longer life expectancy, both of which increase joint loads, as well as wear and tear process [2]. In Saudi Arabia, the prevalence of OA is estimated at 53.3% in males and 60.9% in females, with ages ranging from 30 to 90 years and a mean age of 49 years [3].
The development of OA is primarily associated with two mechanisms: abnormal loading on normal cartilage or normal loading on abnormal cartilage. These mechanisms represent the main risk factors for knee OA [1]. The clinical features of knee OA include joint inflammation [4], articular cartilage degeneration [5], joint instability [6], pain, and functional loss [7]. These signs and symptoms limit activities of daily living (ADL) and can progress to significant functional impairment and disability [7]. Generally, short- and long-term goals for treating knee OA focus on reducing pain, minimizing inflammation and swelling, improving proprioception, and enhancing functional activity and quality of life [7]. There are several treatment options for knee OA include anti-inflammatory drugs, therapeutic exercises, weight management, and physical therapy modalities [8].
Evidence-based guidelines for knee OA management recommend various interventions, including closed kinetic chain exercises (CKCEs), open kinetic chain exercises (OKCEs), aerobic exercises, strength training, and weight management [9–15]. CKCEs are typically performed with the feet fixed to an object, generating compressive forces in the ankle, knee, and hip joints [16]. These exercises have been shown to enhance muscle strength, proprioception, and neuromuscular control in the lower extremities [16]. While CKCE offers potential biomechanical benefits, its clinical efficacy compared to other physical therapy modalities or no treatment remains unclear. Several systematic reviews have examined physical therapy’s role in OA management, but most have evaluated mixed exercise interventions without specifically focusing on CKCE. Moreover, methodological inconsistencies across studies have led to conflicting findings [17–21], with no standardized treatment protocol established. To address these gaps, a systematic review with meta-analysis is needed.
This study aimed to systematically review and conduct a meta-analysis on the effectiveness of CKCE in individuals with knee OA. Specifically, this review aimed to: (1) assess the effects of CKCE on pain reduction compared to no treatment or other physical therapy interventions; (2) assess its impact on functional improvement relative to no treatment or other physical therapy interventions; (3) determine whether CKCE enhances proprioception compared to no treatment or other physical therapy interventions; (4) examine the effects of combining CKCE with other physical therapy interventions to determine whether combined therapy provides greater clinical benefits than individual interventions alone; and (5) evaluate the methodological quality and overall level of evidence.
2. Methods
2.1. Study design
This study was a systematic review and meta-analysis. The systematic review protocol was registered in PROSPERO (registration number: CRD42022316670) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (S1 Table).
2.2. Study strategy
The searches were conducted across nine electronic databases from January 1, 2010, to December 31, 2023, to ensure the inclusion of the most recent and relevant evidence from the last decade, reflecting current advancements in knee OA management. The search strategy was based on the PICO framework. A systematic search was performed in the following databases: PubMed, MEDLINE, Web of Science, EBSCO, Wiley Online Library, Science Direct, Scopus, PEDro, and Cochrane (CENTRAL). The Medical Subject Headings (MeSH) terms used in the MEDLINE database included: weight-bearing exercise program, weight-bearing strengthening program, resistance training, and knee osteoarthritis. Additional terms used in the search were: closed kinetic chain exercise, CKCE, weight-bearing exercise, progressive loading exercise, knee osteoarthritis, knee osteoarthrosis, and knee joint degenerative disease. The search also included the Grey Literature Report, OpenGrey databases, and ResearchGate. Furthermore, references of all eligible articles were screened for relevant studies.
2.3. Eligibility criteria
Studies were eligible if they met the following criteria (S2 Table): randomized controlled trials (RCTs) or clinical trials that investigated CKCE in the treatment of individuals with knee osteoarthritis; CKCE applied to at least one group; participants of any age (18+), sex, or race; pain and function as primary outcomes or proprioception as a secondary outcome; and full text available in English. Studies were excluded if they were not clinical trials (e.g., observational, cross-sectional, or case-control studies); both groups received CKCE; there was no control group; outcome measures (e.g., pain, function, and proprioception) were not assessed; or the full text was unavailable (e.g., abstracts, conference papers).
2.4. Study selection
An initial screening of titles and abstracts was conducted to assess eligibility. Duplicates were removed using EndNote X9 software (Clarivate Analytics, Philadelphia, PA, USA). Full-text articles that met the inclusion criteria were reviewed. To minimize bias, two reviewers (AF and NAA) independently performed the screening and study selection. Any disagreements were resolved in consultation with a third reviewer (MSA).
2.5. Data extraction
Data extracted included participant characteristics (e.g., age and sex), sample size, study design, outcome measures (e.g., pain, function, and proprioception), interventions (type, duration, and frequency of exercises), follow-up assessments, and a summary of results. The mean and standard deviation (SD) of outcome measures (when available) for both experimental and control groups were extracted. For missing data, the primary authors of the relevant studies were contacted to request the data. Two reviewers (AF and NAA) independently collected the data, and any discrepancies were reviewed and resolved by a third reviewer (MSA).
2.6. Methodological quality
Two independent assessors (AF and NAA) evaluated the methodological quality of each study using the PEDro scale. This scale is considered an internally valid and reliable tool for assessing the risk of bias for RCTs and clinical trial, and is commonly used in systematic reviews [22,23]. The PEDro scale consists of 11 items (yes/no questions). The first item assesses external validity, while items 2–11 assess internal validity. Scores range from 0 to 10, and study quality is classified as low (≤3), fair (4–5), or high (>6). Any scoring discrepancies were resolved by consensus with a third reviewer (MSA).
2.7. Quality of evidence
The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system [22], which provides a structured process for summarizing and presenting evidence. GRADE ratings range from very low to high quality and are based on five criteria: (1) study limitations, (2) inconsistency, (3) indirectness, (4) imprecision, and (5) publication bias [25]. Each criterion may be rated as having minimal, serious, or extremely serious limitations [25].
2.8. Data analysis
Qualitative (descriptive) data were presented in tables. Quantitative analysis was conducted through meta-analysis using RevMan software (version 5.3). Pain and function were considered primary outcomes, while proprioception was considered a secondary outcome in the meta-analyses assessing CKCE’s effectiveness in individuals with knee OA. A random-effects model was used, and overall and individual study effect sizes were estimated using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Effect sizes were categorized as small (0.2), medium (0.5), or large (≥0.8) [23]. The percentage of total variability due to between-study heterogeneity was assessed using the I² index, which can be classified as low (I² ≤ 25%), moderate (I² 26–50%), or high (I² ≥ 75%) [24]. A subgroup meta-analysis was performed to compare the effects of CKCE to other treatments.
3. Results
3.1. Study selection
A total of 3,853 articles (1936 articles from databases and 1,917 articles from other sources; Fig 1 and S3-S4 Tables) were identified, of which 715 duplicates were removed. After reviewing the titles and abstracts of the remaining 3,138 articles, 3,086 irrelevant articles were excluded. Following full-text screening, 28 more articles were removed for not meeting the eligibility criteria, leaving 24 studies [17–21,25–43] included in this systematic review. Fig 1 illustrates the PRISMA flow diagram.
3.2. Study characteristics
This systematic review included 1,383 participants, with ages ranging from 30 to 80 years. The experimental group had 555 participants, while the control (no treatment or other treatment modalities) group had 627. Fourteen studies [17,20,21,25–27,30,34,35,37,38,40,42,43] included participants of both sexes (n = 894), with a male-to-female ratio of 232/662. Five studies [19,28,29,31,32] included only female participants (n = 223), while five studies [18,33,36,39,41] did not report the participants’ sex (n = 266). Sixteen studies [17,18,21,25–27,29,32,34–40,42] included individuals with mild-to-moderate knee OA, and one study [20] included individuals with a mixed presentation of knee OA (mild, moderate, and severe). Eight studies did not provide sufficient information regarding the grade of knee OA [19,28,30,31,33,41,43]. Table 1 shows the study characteristics.
3.3. Outcome measures
Pain was evaluated in 20 studies [17–21,27–30,32,34–43] using various tools, including the Visual Analog Scale (VAS) [17–19,21,32,34,35,37–39,42] (n = 11), Numeric Pain Rating Scale (NRS) [20,41] (n = 2), Western Ontario McMaster Universities Arthritis Index (WOMAC) subscale [27–30,43] (n = 5), Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale [36] (n = 1), and pain pressure threshold (PPT) [40] (n = 1). Four studies did not assess pain [25,26,31,33]. Function was evaluated in 22 studies, using tools such as the WOMAC subscale [18,20,25–31,33,34,37–41,43] (n = 17), KOOS subscale [32,42] (n = 2), Ibadan Knee/Hip Osteoarthritis Outcome Measure (IKHOAM) [35] (n = 1), Functional Index Questionnaire (FIQ) [17] (n = 1), and the Six-Minute Walk Test (6-MWT) [21,36] (n = 2). One study did not assess function [19]. Proprioception was assessed in only three studies [21,25,26] via joint repositioning error tests. Table 1 demonstrates the outcome measures used for each study and main results.
3.4. Interventions
In the experimental group, 14 studies [17,19–21,25–28,30,35,38–40,43] used CKCE as the sole intervention, while 10 studies [18,29,31–34,36,37,41,42] combined CKCE with conventional physical therapy (CPT). CPT included a variety of therapeutic modalities, such as hot packs, stretching exercises, and electrotherapy. In the control group, six studies [19,20,28,39,40,43] used OKCE, nine studies [17,18,31–33,35,37,41,42] used CPT, and 10 studies [21,25–30,34,36,38] had no treatment group. The intervention durations varied from 10 days to 12 weeks. Only two studies provided follow-up data after one month of intervention [32,36], while the others did not report follow-up data. Table 2 shows the prescription of each intervention used in the included studies.
3.5. Risk of bias assessment
The methodological quality of the included studies, assessed using the PEDro scale, ranged from 3/10–8/10. Nine studies were rated as high quality [20,21,26–28,30,34,40,43], 13 studies as fair quality [17,25,29,31–33,35–39,41,42], and two studies as low quality [18, 19]. Detailed results are presented in Table 3.
3.6. Quality of evidence
To evaluate the level of evidence (Table 4), studies were categorized by intervention type. The comparison between experimental and control treatments was subdivided into CKCE vs. no treatment and CKCE vs. other treatments. GRADE indicated a low level of evidence for improvements in pain and function, primarily due to study limitations (e.g., low quality on the PEDro scale), inconsistencies (e.g., high heterogeneity), imprecision (e.g., wide confidence intervals with small sample sizes), and publication bias (e.g., inclusion of only positive results).
3.7. Data synthesis
3.7.1. Descriptive analysis.
Descriptive analysis was performed for all included studies, and the main findings are reported in Table 1.
3.7.2. Meta-analysis.
Eighteen studies were included in the meta-analysis. Six studies were excluded due to missing information (e.g., mean and standard deviation for both the experimental and control groups) [18,25,30,32,40,41].
The overall effect size of CKCE (experimental) vs. no treatment (control) on pain reduction was analysed in three studies [21,27,28], and CKCE vs. other treatments was analysed in 12 studies [17,19,20,28,29,34,35,37–39,42,43]. The overall meta-analysis showed that CKCE significantly reduced pain compared to no treatment (SMD = −0.76; 95% CI: −1.51, −0.01; I² = 76%; P < 0.05; Fig 2), but there was no significant difference between CKCE and other treatments (SMD = −0.18; 95% CI: −0.55, 0.19; I² = 78%; P = 0.34; Fig 3).
Functional improvement (WOMAC, the lower the score, the better the result/function) was assessed in three studies comparing CKCE vs. no treatment [26–28] and in 11 studies comparing CKCE vs. other treatments [20,26,28,29,31,33,34,37–39,43]. The overall meta-analysis revealed significant improvement in function for CKCE vs. no treatment (SMD = −1.25; 95% CI: −1.88, −0.62; I² = 66%; P < 0.0001; Fig 4) and CKCE vs. other treatments (SMD = −0.74; 95% CI: −1.23, 0.26; I² = 85%; P = 0.002; Fig 5). Four studies [17,35,36,42] employed different scales (the higher the score, the better the result/function) to evaluate the improvement of function such as IKHOAM, FIQ and KOOS. For these other scales of function, the overall meta-analysis revealed no significant difference between CKCE and other treatments (SMD = 0.07; 95% CI: −0.43, 0.56; I² = 58%; P = 0.79; Fig 6).
3.7.3. Subgroup meta-analysis.
Subgroup meta-analyses showed significant results in certain comparisons. For example, CKCE + CPT significantly reduced pain [29,34] compared to CPT alone (SMD = −1.18; 95% CI: −1.70, −0.67; I² = 0%; P < 0.00001; Fig 3). Similar findings were observed for functional improvement [29,34], where CKCE + CPT provided better results than CPT alone (SMD = −1.27; 95% CI: −1.79, −0.75; I² = 0%; P < 0.00001; Fig 5). However, no significant differences were observed between CKCE and other treatments like OKCE or manual therapy in either pain or function outcomes.
4. Discussion
This systematic review and meta-analysis yielded several important findings. First, the meta-analysis indicates that CKCE has a medium effect size in reducing pain and a large effect size in improving function in individuals with knee OA compared to no treatment. Second, the meta-analysis also suggests that CKCE, either alone or in combination with other treatments, has a medium effect size in improving function compared to treatments without CKCE. Third, the subgroup meta-analysis indicates that CKCE combined with CPT has a large effect size in improving function compared to CPT alone. Fourth, the risk of bias assessment revealed that more than half of the included studies were of high quality according to the PEDro scale. However, the GRADE assessment indicates low-quality evidence regarding the effects of CKCE (alone or combined with other treatments) on pain reduction and functional improvement.
Evidence-based guidelines for treating knee OA endorse both land- and water-based CKCE [9–14]. CKCE is more effective because it encourages the use of lower limb muscles during daily activities, facilitating more effective contractions, including both eccentric and co-contractions, with simultaneous segmental movement [31]. CKCE predominantly involves eccentric muscular work, which increases muscle tension [44]. Additionally, CKCE minimizes shear forces while increasing compression forces and controlling the chain of motion across the joint, improving joint stability [31]. Therefore, CKCE is considered an effective functional exercise that enhances muscle strength and proprioception.
The results of this meta-analysis reveal significant improvements in pain and function with CKCE treatment compared to no treatment. This finding is based on the pooled results of three studies [26–28], which demonstrate CKCE as an effective treatment for pain reduction in individuals with knee OA. Reducing pain intensity and improving function may enhance the ability to perform ADLs, such as walking, increasing gait speed, and climbing stairs [27]. However, not all studies in the meta-analysis reported significant effects of CKCE compared to no treatment [21]. Discrepancies in results may be due to differences in treatment protocols between studies, where increased exercise intensity may have exacerbated pain.
In the subgroup meta-analysis, both CKCE and OKCE showed significant pain reduction, but the differences in magnitude between CKCE and OKCE were not significant [17,19,20,28,35,43]. A similar finding was observed when comparing CKCE + CPT to OKCE + CPT, where both treatment groups experienced significant pain reduction, but there was no significant difference between them [37,42]. However, CKCE + CPT had a significantly greater effect on pain reduction compared to CPT alone [29,34], suggesting that incorporating CKCE into conventional rehabilitation programs provides additional benefits. The subgroup meta-analysis also showed no differences in pain reduction between CKCE and other interventions, such as manual therapy. However, this finding may be limited by the small number of available studies [38] and the small sample sizes, which may have reduced the statistical power needed to detect differences between groups.
For functional improvement (WOMAC), subgroup meta-analysis indicated that both CKCE and OKCE had a similar beneficial effect on function, with no significant differences between the two treatments [20,26,28,31,43]. However, the evidence leaned in favour of CKCE, as two studies favoured CKCE over OKCE [31,43], and three studies [20,26,28] found comparable results between the two treatments in terms of functional improvement. The additional benefit of CKCE might be explained by its resemblance to many ADLs, such as sitting up, stair climbing, and squatting. Incorporating these exercises into the training program may better facilitate these functional activities than other exercises like OKCE. When CKCE + CPT was compared to OKCE + CPT, both treatments showed significant functional improvements, but no significant differences were found between them [37]. However, CKCE + CPT significantly improved function compared to CPT alone [29,34]. Similar to pain reduction, no significant functional differences were found between CKCE and manual therapy [38]. For functional scales other than WOMAC, the overall meta-analysis showed no differences between CKCE and other treatments [17,35,36,42].
Although meta-analysis for joint proprioception could not be performed due to missing required data (e.g., means and standard deviations), three studies investigated joint proprioception and compared CKCE to no treatment [21,25,26]. Two studies [25,26] found a significant difference between CKCE and the control, while one [21] reported no significant difference.
In general, there were serious inconsistencies when comparing CKCE with no treatment (for pain) and when comparing CKCE with other treatments for pain and function (e.g., WOMAC). These inconsistencies may be due to differences in sample size, intervention type and duration, number of sessions, exercise intensity, and progression.
Several limitations may affect the generalizability of the results, and the current evidence (GRADE) indicates low-quality evidence for the effects of CKCE on pain and function in individuals with knee OA. This could be due to several factors: (1) most studies had small sample sizes, (2) the type and intensity of training were inconsistent between studies, (3) the percentage of total variability due to between-study heterogeneity was moderate to high, and (4) most studies lacked long-term follow-up data. These factors may have impacted the accuracy of the results, making it difficult to establish clinical recommendations based on the existing evidence. Therefore, high-quality trials are needed.
5. Conclusion
Although CKCE shows promise as a treatment for individuals with knee OA in terms of pain reduction and functional improvement, the low quality of the studies limits confidence in the effect estimates. Further long-term, high-quality RCTs with large sample sizes are required.
Supporting information
S4 Table. Study selection and inclusion/exclusion criteria through primary sources.
https://doi.org/10.1371/journal.pone.0322475.s004
(XLSX)
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