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Abstract
Introduction Epidemiological literature indicates that sarcopenia (SA) is increasingly prevalent among patients with knee osteoarthritis (KOA). This study aims to provide the pooled prevalence of SA and identify determinant factors associated with SA among patients with KOA.
Methods and analysis This systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) auxiliary writing checklist. A thorough literature review and systematic search will be performed using the electronic databases of PubMed, Web of Science, Embase, CNKI and WanFang, covering the period from the earliest records until 11 September 2024. Reference lists of the eligible studies will also be carried out. The search strategy will be based on two main concepts, namely ‘knee osteoarthritis’ and ‘sarcopenia’, taking the form of a combination of MeSH terms and entry terms to find literature. Two reviewers will independently evaluate each title and abstract. All observational studies documenting the prevalence of SA and/or associated factors in KOA will be included. The prevalence of SA will be subjected to a single-group meta-analysis using Stata 18.0 software. Pooled prevalence with a 95% CI will be calculated using random effects and quality-effects models. The pooled relative hazards will be calculated using a random-effects Meta-analysis. The main analysis results will include differences in the prevalence of SA in KOA patients by diagnostic criteria, course of KOA, disease status (eg, knee pain, disease duration), physical activity, diagnostic criteria and different geographical contexts. Secondary results may analyse subgroups such as gender and age, and further, a meta-regression analysis will be used to synthesise the factors influencing SA. Sensitivity analyses and heterogeneity between studies and evidence of publication bias will also be assessed.
Ethics and dissemination This review will summarise the prevalence and influencing factors of SA in patients with KOA based on existing evidence. It is expected that the results will identify gaps in knowledge and areas for further research. The review will be submitted for publication in topic specific journals and disseminated to professional networks. Individual patient data are not included, so ethical approval is not required.
PROSPERO registration number CRD42023490539.
- Patients
- Knee
- Aging
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STRENGTHS AND LIMITATIONS OF THIS STUDY
A comprehensive search strategy across multiple databases, ensuring specificity, transparency and reproducibility of the search criteria.
Utilisation of standardised literature quality assessment tools provided by JBI, which ensures robustness and consistency in data evaluation.
Advanced statistical methods, including meta-analysis, meta-regression and subgroup analysis, provide precise estimates of sarcopenia (SA) prevalence and enable the identification of predictors and sources of heterogeneity.
Only observational studies are included which may not capture all factors influencing SA.
Limiting the search to Chinese and English literature may affect the generalisability of the study results and leave potential residual confounding factors unresolved, relying solely on the data from included studies.
Background
Rationale
Sarcopenia (SA) is characterised by the decline in muscle mass, strength and physical functionality. It is a novel, age-accelerating affliction of the musculoskeletal system. The prevalence of SA in the USA reaches 75% of the population aged 50 years or older.1 SA is commonly associated with weakness, falls, fractures and disability in susceptible individuals2–4 and can lead to severe functional impairment and hypermobility.1 It has attracted the attention of the international geriatric health research community in recent years. An article from the Lancet5 indicates that SA has various frequent underlying causes. For example, inadequate nutritional intake such as low protein intake, micronutrient deficiencies and anorexia (ageing, oral problems) are some of these factors. Furthermore, extended bed rest, minimal activity and a sedentary lifestyle have been identified as risk factors for the development of SA. Disease, particularly chronic disease, has been identified as a risk factor in numerous studies, including those concerning bone and joint disease. Kemmler et al 6 found that patients with hip and lower extremity osteoarthritis (OA) were more likely to develop SA than those without OA (9.1%: 3.5%).
Knee osteoarthritis (KOA) is associated with a substantial risk for the development of SA.7 KOA and SA are both age-related conditions. KOA is characterised by progressive cartilage loss, changes in the surrounding bone and associated low-grade local inflammation.8 9 Physical symptoms are mainly knee pain and functional limitations, and patients often adapt to a sedentary state with reduced physical activity.10 Subsequently, sedentary lifestyle and lack of physical activity in turn reduce energy expenditure and lead to muscle wasting, which reduce joint protection.11 This is due to changes in the biomechanical structure of the joints as muscle mass and strength decline, leading to decreased joint stability and consequently accelerating the degeneration of joint cartilage. An animal study finds that muscle atrophy causes changes in the microstructure of subchondral bone in the articular cartilage of mice.12 13 Thus, SA and KOA may be mutually reinforcing relationships. Furthermore, the progressive nature of KOA means that it requires advanced treatment options in a later period to reduce pain, improve function and maintain life quality. The definitive treatment is total knee arthroplasty (TKA). Globally, more than 1 million TKA are performed annually.14 However, preoperative SA may have a negative impact on postoperative recovery in TKA patients. Preoperative SA in KOA patients delays postoperative activity recovery15 and elevates complication risks,16 17 such as prosthetic infections. Consequently, understanding the prevalence and influencing factors of SA in KOA patients can aid in early detection, diagnosis and intervention, thereby improving patient outcomes.
Previous researches have conducted primary investigations into the prevalence of SA and its associated risk factors in patients with KOA; however, the varying results across these studies limit their clinical applicability. Several original studies have shown SA prevalence among patients with KOA from 4.48 to 35.5%.11 18–20 Park et al 18 determined the prevalence of SA in Asian female patients awaiting primary TKA due to advanced KOA using the updated AWGS criteria. The prevalence of SA was 35.5%, and severe SA was 21.7%. Influencing factors included low body mass index and lower 25-OH-vitamin D3 levels. Godziuk et al 19 investigated 151 patients with end-stage KOA and found that the prevalence of sarcopenia obesity (SO) was 8.6%, and SO exacerbates KOA-related physical disability. Liao et al 20 used bioelectrical impedance and step speed to determine the SA prevalence in patients with end-stage KOA and produced results ranging from 4.48% to 32.39% with different diagnostic criteria.
We had conducted a literature search prior to December 2023 to ensure that we were aware of the latest relevant studies up to that point. To our knowledge, only one review21 has previously addressed the prevalence of SA in KOA patients. Nevertheless, the review possesses multiple limitations: first, it encompassed merely four studies, two of which diagnosed SA exclusively based on diminished muscle mass, potentially introducing bias. Since low muscle mass identifies only an early stage of SA rather than the condition itself, additional measures such as physical performance or muscle strength are required to ensure diagnostic accuracy. Second, the review’s search was last updated on 22 February 2022, and it is evident that additional literature meeting the inclusion criteria has been published since then.11 22 23 In addition, China, as a seriously ageing country, already has the world’s largest older population,24 but previous studies have not been included in Chinese databases for searching. Consequently, it is imperative to update the literature for a systematic evaluation. Most importantly, the review did not perform a pooled analysis of factors influencing SA occurrence in KOA patients. Similarly, the only protocol25 we are aware of that is like our research but with a broader scope, which examined the relationship between SA and osteoarthritis (including hip, knee, and spinal joints), also did not explore modifiable influencing factors. However, exploring modifiable factors influencing SA in KOA patients will assist healthcare professionals in developing interventions to prevent and mitigate the impact of on those with the condition. Information about the prevalence and influencing factors may help surgeons and nurses more appropriately select and educate their patients and improve the health and care of populations or communities. Therefore, it is important to further refine the above limitations and develop a new systematic evaluation.
Objectives
Consequently, we will conduct a systematic review to enhance prior reviews and examine the prevalence of SA in the KOA population, using available published data. The review aims to solve the following questions:
Investigate the prevalence of SA and sarcopenic obesity among KOA patients.
Conduct an in-depth analysis of modifiable risk factors and potential protective factors (defence mechanisms) influencing the onset of SA in KOA patients.
Perform subgroup analyses to uncover the diversity of SA characteristics within a specific research cohort (namely, patients with KOA), including: (1) severity of KOA, (2) disease status (eg, knee pain, disease duration), (3) levels of physical activity, (4) varying diagnostic criteria and (5) different geographical contexts.
Methods
This protocol adheres to the PRISMA Protocols (PRISMA-P),26 and it was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 23 December 2023 (registration number CRD42023490539). PROSPERO will be updated with significant protocol amendments. The final synthesis will be reported following the JBI Prevalence and Incidence Review Manual.27
Definition of terms
Sarcopenia
Our study will include cases with a confirmed diagnosis of SA, encompassing patients identified and reported via screening (table 1). The definition of SA has undergonec multiple phases. When first used, it referred to age-related loss of muscle mass and function.28 The European Working Group on Sarcopenia in Older People (EWGSOP) in 2010 defined SA using muscle mass, muscle strength and physical performance (updated their definition in 2019 (EWGSOP2) with cutoffs defined;).29 30 The Asian Working Group on Sarcopenia in 2014 gave the same definition as the EWGSOP and defined cutoffs for Asia.31
2018 operational definition of SA30
We will focus primarily on studies that have measured muscle mass and grip strength (or stride speed/physical performance) and give due consideration to studies that have measured only muscle mass or muscle strength (eg, articles published before the definition of SA were released).
Knee osteoarthritis
This review will concern the grading of osteoarthritis of the knee, including Kellgren-Lawrence grade, Lequesne grade or WOMAC grade. In addition to the above criteria, in this review, the KOA before TKA will be considered in the end stage. Finally, if conditions permit, we will combine the various criteria to categorise a uniform determination of the course of osteoarthritis of the knee.
Eligibility criteria
Studies will be included if they:
Are original studies published in peer-reviewed journals. Examine the prevalence (inclusion of impact factor analysis or not) of SA among KOA patients. When studies include a sample partially composed of KOA patients, we will extract the information needed to calculate the prevalence.
Use any clearly stated SA definition: reporting a diagnosis of KOA and using radiological and/or medical information. Those studies with patients with total knee replacements caused by osteoarthritis of the knee will also be considered.
Use data from an observational study, such as prospective and retrospective cohorts, cross-sectional and case-control studies.
Are written in English or Chinese. English and Chinese, the most spoken languages worldwide, offer extensive research data. Our team’s bilingual expertise ensures precise literature evaluation.
Studies will be excluded if they:
Are dissertations and theses, reviews, conference proceedings, editorials and letters.
Information sources and search strategy
Relevant studies will be identified via an electronic search. The chosen databases include PubMed, Web of Science, Embase, CNKI and Wanfang, which will be accessed via Central South University Library interface (https://libdb.csu.edu.cn/). From the earliest records until 11 September 2024, these databases will be searched. The initial search started with the terms ‘knee osteoarthritis’ and ‘sarcopenia’. After the identification of potentially modifiable risk factors, the search will be extended using each modifiable factor as a keyword. Accordingly, MeSH terms and relevant free-text terms will be used. The search strategy is based on SA terms, study terms, moderators and limits. The search comprises both Medical Subject Headings (MeSH) and free text words (title and abstract word searches). Use Boolean logic operators, proximity operators, truncation symbols and other search terms to combine them for comprehensive retrieval. We will collaborate with librarians to investigate and formulate search strategies customised for different databases. Using the Embase database as a case study, we will employ its exclusive EMTREE thesaurus for our searches. The use of the EMTREE thesaurus significantly enhances search precision, as it offers a structured search method similar to the MeSH, allowing for more precise matching and effectively filtering out literature resources highly relevant to the research topic. Additionally, review the references of the included studies for further relevant literature.
We intend to progressively adjust the search strategy to align with each database until an optimised approach for each database is established. Table 2 delineates the search terms and various search tools employed for the distinct databases. The full electronic search strategies using PubMed as an example are included in online supplemental information 1. The reference lists of fully eligible texts will also be screened to identify potential inclusions. We will contact the authors when additional information is required. The study will start in September 2024 and end on submission of the study report for publication-expected in December 2024. We will routinely update our searches to incorporate the latest research findings.
Supplemental material
Search strategy
Study selection
Retrieved records will be imported into EndNote 20 software for management, and duplicates will be removed. Three researchers will participate in the review panel. The first author (GYB) who has participated in conducting several systematic reviews as first and coauthor, together with the second author (ZY) who recently completed an intensive course on how to conduct systematic reviews and meta-analyses, will independently screen the titles and abstracts of all studies using a template to determine whether the inclusion criteria are met; if there is disagreement, the third reviewer (ZBY) will share judgement.
The full text of the remaining articles will be retrieved. Inaccessible articles will be dealt with by contacting the authors directly. Each full text will undergo independently evaluation by two of the three researchers to determine final eligibility. Record and document the reasons for rejected studies at each stage (table 3). Any differences between researchers will be resolved through discussion. Figure 1 represents a flow diagram of the study selection process.
Flow chart of study selection. Create a literature screening flowchart for this study based on the PRISMA 2020 flow diagram. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analysis.
Details of excluded literature
Data extraction
Use the Zotero reference manager to conduct full-text reading of the included literature. Create standardised information extraction forms using Excel 2016 (table 4); three reviewer authors will independently extract data from eligible studies including the first author’s last name, year of publication, study location, sample size, study design, SA definition, SA diagnosis, SA measurement, SA type, data on prevalence of SA, ascertainment of outcome, risk or protective factors examined in each study together with their respective OR and 95% CI, and information for assessment of the risk of bias. The final table will be based on the characterisation of actual studies obtained, which will be a dynamic process. If the same datasets were used in more than one study, the report will be considered a duplicate, and our review will incorporate the study that reported the most comprehensive dataset.
Details of the literature included
Quality assessment
The quality of the study will be evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal tools.32 The JBI offers a suite of critical appraisal tools available for free use by systematic reviewers and researchers to investigate the methodological limitations of articles. The JBI tools are specifically designed for studies and are presented in the form of checklists.33 All the response formats to the questions in the checklist were ‘low risk’, ‘unclear’ and ‘high risk’. Discrepancies in quality assessment among the reviewers were adjudicated by a third reviewer. Studies that affirmatively respond to over six items satisfy the fundamental criteria for inclusion in this systematic review.34 For this review, two independent reviewers will use a checklist based on these tools, which can be found in online supplemental material 2.
Supplemental material
Synthesis
Narrative synthesis
A descriptive summary of the studies will be provided using tables. The following areas will be addressed: SA definition, SA type, SA measurement, gender, age, location and study quality assessment. Whittemore and Knafl’s comprehensive review methodology will serve as a guide for narrative synthesis.35 Comments on the similarity of methods used in different studies and the possibility of conducting meta-analysis.
Meta-analysis
A meta-analysis of pooled prevalence analysis will be conducted if sufficient studies yield the pertinent prevalence data and if the justification for their combination is established. Use random-effects and fixed-effects models to calculate the pooled incidence of SA and its 95% CI in KOA patients. These will be presented in a forest plot. Heterogeneity between the studies will be assessed using both Cochrane’s Q statistic and the I2 statistics. I2 value greater than 50% will be considered as indicative of substantial heterogeneity. If there are enough studies included, subgroup analysis will be performed to investigate heterogeneity. The primary analysis results will include subgroups with (1) severity of KOA, (2) disease status (eg, knee pain, disease duration), (3) levels of physical activity, (4) varying diagnostic criteria and (5) geographical contexts. Secondary analysis results may include differences in the prevalence of SA in KOA patients by gender, age, and other factors.
Finally, further analysis of the factors influencing SA in KOA patients will be conducted. A meta-analysis will be performed on risk factors derived from two or more comparable research studies. This meta-analysis will follow standard methodological guidelines to minimise inherent differences among individual studies due to variations in population characteristics, research design and measurement outcomes. To explore the impact of potential moderators on the effect size, we will conduct a meta-regression analysis, including factors such as age, gender, diagnostic criteria, disease severity and other factors. If the included studies have a limited number of extractable factors with significant variability that precludes data pooling for meta-analytic purposes, a descriptive analysis will be performed to examine the impact factors on SA in patients with KOA.
Funnel plots will be used to evaluate publication bias. A sensitivity analysis excluding studies of low quality will be carried out. Double arcsine transformation is used when variance instability is present. All statistical analyses are performed using Revman V.5.3 and the STATA 18.0 Metaprop package.
Reporting
The systematic review’s results will be shared accordance to the PRIMSA 2020 writing checklist.
Patient and public involvement statement
Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Discussion
This systematic review and meta-analysis will be the first comprehensive study to assess the pooled prevalence and influencing factors of SA among KOA patients. This will expand on prior reviews and examine the risk factors and predictors for the development of SA in KOA patients. The study will explore the heterogeneity of findings across different diagnostic criteria, disease status (eg, knee pain, disease duration), severity of KOA, levels of physical activity and geographical contexts. Furthermore, by identifying the risk and protective factors of SA, the findings may help in developing evidence-based musculoskeletal health promotion and disease prevention programmes targeting KOA.
Expected results and impacts on clinical practice and public health
Impact on clinical practice. This study aims to enhance orthopaedic staff awareness of the prevalence of SA in patients with KOA, facilitating proactive identification and screening during clinical assessments. It also aims to help healthcare providers personalise treatment by identifying modifiable predictors of SA, leading to tailored interventions that consider patients’ conditions and activity levels and improve their self-management. Also, the study will foster collaboration across disciplines like orthopaedics, rehabilitation, nutrition and geriatrics for integrated management. Finally, it will guide future research by highlighting knowledge gaps, particularly in exploring the biological underpinnings of SA and developing new therapeutic approaches.
Impact on public health policy. This systematic review will inform health policy for the elderly by enabling public health initiatives for SA and KOA, including promoting suitable physical activities and nutritional advice. It also aids in the efficient use of resources, such as establishing community rehabilitation centres for targeted care. It aims to reduce hospitalisation rates and lower healthcare costs by fostering early detection and intervention and enhancing patient self-management.
Strengths of this study
This study employed comprehensive databases and a well-crafted search strategy. Searching both Chinese and English databases allowed for the capture of epidemiological data on SA within KOA populations from diverse cultural backgrounds. The search strategy incorporated Population, Exposure, Comparator, Outcome, Study design (PECOS), ensuring accuracy and specificity.
This study will employ a combined approach of factor analysis and subgroup analysis in the review, which will enhance our understanding of SA in KOA patients. The objective is to elucidate the progression of SA in KOA patients by discerning critical factors and distinctions among specific demographics, customised to individual attributes (such as gender and region) and stages (severity of KOA and physical activity levels). The study focuses on exploring modifiable risk factors and potential protective factors for SA in KOA patients, which holds significant implications for clinical practice. For instance, identifying the prevalence of SA in KOA patients at various levels of disease severity can provide a basis for stratified diagnosis and treatment and risk stratification for healthcare professionals.
Limitations of this study
This study has two main limitations. First, it is planned to include only observational studies, which may not capture all factors influencing SA, but rather only the modifiable risk factors and protective factors present in the current evidence base. The search will be confined to Chinese and English literature, potentially neglecting important studies in other languages. Nevertheless, considering the team’s predominant use of English and Chinese for academic communication and the comprehensive representation of these languages in scientific literature, the chosen sources sufficiently fulfil our research requirements.
Ethics and dissemination
This review will summarise the prevalence and influencing factors of SA in patients with KOA based on existing evidence. It is expected that the results will identify gaps in knowledge and areas for further research. The review will be submitted for publication in topic specific journals and disseminated to professional networks. Individual patient data are not included, so ethical approval is not required.
Ethics statements
Patient consent for publication
Acknowledgments
We would like to express our gratitude to Mariama Diop from our research team for her meticulous review and editing of our manuscript's grammar.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors YG was the main writer of the PROSPERO protocol registration and contributed to the writing of this manuscript. YZ is the guarantor and contributed with edits and methodological guidance. BZ conducted a preliminary search of the literature. All authors read and approved the final manuscript.
Funding This research is funded by the Research Project of Hunan Provincial Nursing Association (HNKY202202), the Hunan Provincial Natural Science Foundation (2022JJ40766), the Key Research and Development Project of Hunan Province (2024JK2133) and the Teaching Reform Research Project of Hunan Province (2023JGB043).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.