Impact of Multicomponent Physical Exercise and High Intensity Interval Training on Osteoporosis in Postmenopausal Women: protocol for a systematic review and Network meta-analysis of randomized controlled trials

Impact of Multicomponent Physical Exercise and High Intensity Interval Training on Osteoporosis in Postmenopausal Women: protocol for a systematic review and Network meta-analysis of randomized controlled trials | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Multicomponent Physical Exercise and High Intensity Interval Training on Osteoporosis in Postmenopausal Women: protocol for a systematic review and Network meta-analysis of randomized controlled trials Miguel Monteiro, André Schneider, Samuel Encarnação, Pedro Forte, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5456494/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Dec, 2025 Read the published version in Systematic Reviews → Version 1 posted 5 You are reading this latest preprint version Abstract Background: Osteoporosis is a progressive degenerative bone condition leading to increased fracture risk. Therefore, osteoporosis acknowledges around 200 million cases with about 70% of the cases occurring in postmenopausal women. Medicaments are often suggested to treat osteoporotic conditions; but physical exercise also plays an essential role. The current literature highlights multicomponent training (MCT) and high-intensity and high-impact exercises as physical exercise interventions that positively affect postmenopausal womens’ bone health. Furthermore, there is prior evidence of systematic reviews about the positive effects of both methods on the bone health of this population. Despite this prior evidence, no systematic reviews with metanalytic methods compare the effectiveness of the two interventions. Methods and analysis: The study will follow the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number (CRD42024604930). This systematic review and meta-analysis will include only Randomized controlled clinical trials (RCTs), which have verified the effects of one or both physical exercise methods in postmenopausal womens’ bone mineral density (BMD). The systematic search will be implemented at eight electronic databases, namely PubMed/MEDLINE, Web of Science (WoS), EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, CINAHL and SPORTDiscus will be used to retrieve the data of interest. The RCTs ' risk of bias (RoB) will be assessed with RoB 2 Cochrane tool, and between-study heterogeneity will be checked through the analysis of Half-Cauchy distribution. Additionally, a Network meta-analysis will be applied to to compare the between-studies dose-response in the patients’ bone health. Discussion: In this study, we hope to find consistent results about the effects of MCT and HIIT in postmenopausal women with osteoporosis. Therefore, we also expect to observe between-intervention effects after the network meta-analysis approaches. This way, this study will significantly impact this field of knowledge. Ethics and dissemination: The design of this review protocol did not involve patients. PROSPERO registration number: CRD42024604930. Figures Figure 1 Introduction Osteoporosis is a condition defined by decreased bone density and degradation of bone microarchitecture, leading to increased fragility and susceptibility to fractures. The disease can affect various regions of the skeleton, being diagnosed and classified according to the degree of bone loss and history of previous fractures ( 1 ). With an estimated global prevalence of 200 million cases, osteoporosis constitutes a significant public health problem, with considerable economic repercussions ( 2 , 3 ). Approximately 70% of cases occur in women in the postmenopausal phase ( 1 , 4 ). Osteoporosis is a widely prevalent condition and is expected to increase in the coming years. It is estimated that about 30% of women in Europe and the United States have osteoporosis, and at least 40% of these women will suffer one or more fractures related to the disease in their lifetime. The consequences of this condition include a significant reduction in quality of life, compromising functional capacity, independence, and mobility. Additionally, osteoporosis represents a significant risk to life, as one in every three people dies within 12 months after a hip fracture ( 5 ). The primary treatment for osteoporosis usually includes medications aimed at increasing BMD. However, exercises play an essential role in reducing other risk factors associated with falls and fractures, such as muscle weakness, loss of balance, and decreased functional capacity. In order for exercises to provide these benefits, it is crucial that they are correctly prescribed and that the patient maintains proper adherence to the program ( 5 ). Regular physical activity can help minimize bone loss and reduce the frequency of falls and fractures ( 6 ). Although there are studies investigating the benefits of physical exercise for osteoporosis ( 7 , 8 ), there is a scarcity of specific research on the effects MCT and HIIT in treating osteoporosis in postmenopausal women. A comprehensive search in the literature revealed only two systematic reviews with this type of intervention in the studied population. The first one analyzed the effects of HIIT on bone health, but presented limitations, such as consulting a restricted number of databases and the absence of meta-analyses ( 9 ). The second review focused on MCT, but used mixed samples of middle-aged and older women, without conducting subgroup analyses by the participants’ age ( 10 ). Therefore, there is a clear need for studies that include complementary analyses and more robust search strategies, overcoming the limitations of previous works. In face of the limitations identified in previous studies, the need for more in-depth research using broader search strategies and complementary analyses is evident. Future investigations should focus on the role of MCT and HIIT in preventing fractures and improving bone health in postmenopausal women with osteoporosis. Furthermore, despite the importance of diagnostic methods such as dual-energy X-ray absorptiometry (DXA) and tools such as fracture risk assessment (FRAX), few studies analyze these parameters together in the context of physical exercise ( 9 , 10 ). Therefore, more research is essential to clarify the effects of these interventions and provide a solid scientific basis for treatment and prevention strategies in postmenopausal women with osteoporosis. Methods Study Registration The protocol of this study followed the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) (11). The study protocol was prior registered at the International prospective register of systematic reviews (PROSPERO) under the registration number CRD42024604930. Eligible criteria for study selection Types of studies RCTs reviewed by peers and published in English language since the most relevant scientific literature is published in peer-reviewed journals which are written in English, thus ensuring greater scope and reliability for the study. Moreover, the search will encompass the last ten years of scientific literature (2014-2025) will be included in the search, . Grey literature was excluded, as the studies included in the academic repository could still not be peer-reviewed article. A wide collection of peer-reviewed studies is already available. Types of participants The eligible participants will be postmenopausal women diagnosed with a bone BMD T-score of less than or equal to -2.5. The inclusion criteria will be strictly limited to females, focusing exclusively on postmenopausal women. Studies with mixed populations of men and women will be excluded. However, there will be no restrictions regarding ethnicity, severity of symptoms, or disease duration. Types of interventions and comparators We will include treatments in which osteoporosis has been diagnosed based on BMD measured only with gold standard equipment i.e., DXA (12). The study compares the effects of two types of exercise interventions—high-intensity interval training (HIIT) and multicomponent training (MCT)—on this condition (13,14). Interventions must have a duration of at least 8 months. HIIT sessions involve alternating periods of high-intensity exercise, where the body works close to its maximum capacity (above 80% of maximum heart rate or 90% of the VO 2 max), with short periods of low-intensity recovery can involve rest or light active movement (below 50% of the maximum heart rate or below zones of 30-40% of VO 2 max)(15). The HIIT exercises performed in the included studies can be characterized by multiple kinesiologic types: running (16), cycling (17), or circuit training (18) since they reach the required intensities of the HIIT method. In contrast, MCT sessions refer to physical exercise interventions that incorporate two or moretypes of exercise, with common components including aerobic, resistance, and balance training commonly performed at moderate intensities (70% of maximum repetitions for strength, bellow 70% of the VO 2 max for aerobics and moderately challenging to balance exercises) (19). Types of outcome measures The primary outcome will be the mean differences in bone mineral density (BMD), while the secondary outcome will focus on mean differences in physical fitness. Physical fitness will be assessed using standardized functional tests, such as the Short Physical Performance Battery (SPPB) (20), the Senior Fitness Test (21), and other similar assessments commonly reported in the literature, ensuring consistency and comparability of results across studies. Search strategies for the identification of studies Electronic searches The search was updated to ensure that the final search date is as current as possible, and it was completed on January 18, 2025, guaranteeing the inclusion of the most recent and relevant studies. The following electronic databases were searched: PubMed/MEDLINE, Web of Science (WoS), EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, CINAHL, and SPORTDiscus. Specific search strategies validated for identifying randomized controlled trials (RCTs), such as those recommended in the Cochrane Handbook, were used as references to construct the queries. These strategies included Medical Subject Headings (MeSH) and equivalent terms, which were adapted and enriched for each database to ensure comprehensiveness. Detailed search strategies are presented in Figure 1. Filters were minimized to avoid the exclusion of relevant studies, focusing only on essential criteria, such as publication type (RCTs) and language (English), as outlined in Table 2. Data collection and analysis Study selections The potentially relevant articles will be evaluated for eligibility through screening of titles and abstracts, and subsequently selected after a full-text review based on previously defined inclusion and exclusion criteria. The literature search and selection process will be initially conducted by two reviewers and then verified by a third author. Any disagreement will be resolved through discussion among the three authors. All studies will be managed and stored using Rayyan, an online platform tool for systematic review and meta-analysis (https://www.rayyan.ai/) (22), The reasons for excluding studies will be recorded and presented in a PRISMA flowchart. Data extraction and management The relevant data from each study, including year of publication, sample size, participants' characteristics (e.g., age and T-score), and training modalities (type of exercise, frequency, and duration), will be extracted using a standardized and previously established Microsoft® Excel spreadsheet. Two reviewers will conduct The extraction process independently, and any discrepancies will be resolved through discussion or consultation with a third reviewer. All extracted data will be managed and analyzed in R Studio. Additional data will also be collected, such as intervention details, primary and secondary outcomes, and study design. where necessary, data transformations will be performed, including unit conversions, normalization, calculation of means or standard deviations, and effect sizes of treatments to ensure consistency across the study comparison (23). A sensitivity analysis will be conducted to evaluate the robustness of the results, accounting for factors such as sample size, high risk of bias 2 (RoB 2), missing data, and the analytical models used. Studies with low methodological quality after assessment will be excluded to maintain the reliability and validity of the findings (23). Calibration exercises for study selection and data extraction Calibration exercises will be conducted before the formal study selection and data extraction processes to ensure consistency and accuracy among the reviewers. Two independent reviewers will screen a pilot set of 10 randomly selected articles, evaluating them against the inclusion and exclusion criteria. Discrepancies will be discussed and resolved in consultation with a third reviewer to refine the application of the criteria during the article screening. Similarly, for data extraction, the same prior-trained reviewers will independently extract data from five studies using a standardized extraction form. Any disagreements will be resolved through discussion or consultation with the third reviewer. These reading exercises will ensure that all reviewers are aligned and reduce variability in decision-making during the review process. Assessment of RoB and quality The Cochrane Collaboration tool for assessing RoB 2 will be used to evaluate the RoB for randomized clinical trials (24). It contains five bias domains: bias due to the randomization process, deviation from intended intervention, missing outcome data, measurement of outcomes, selection of the reported result, and “overall risk of bias” judgment (25). Studies with low methodological quality will be excluded based on the results of the risk of bias assessment using the Cochrane Risk of Bias Tool 2.0 (RoB 2.0). Low methodological quality will be defined as studies rated as “high risk of bias” in two or more of the five domains assessed by RoB 2.0, including bias arising from the randomization process, bias due to deviations from intended interventions, bias due to missing outcome data, bias in measurement of the outcome, and bias in selection of the reported result. Additionally, studies that lack essential methodological details required to make an informed judgment, even after contacting the authors for clarification, will also be classified as low quality. Consistent concerns about methodological integrity, such as unclear allocation concealment, incomplete outcome data, or selective outcome reporting, will further support the classification of low quality. Managing missing data In case of missing, inadequate or confusing data, we will contact the corresponding author to request the essential information. If it is not possible to obtain this information, only the accessible data will be used in the analysis, with the limitations duly discussed. Assessment of heterogeneity The between-studies heterogeneity (T2) assessment will be performed in R, programming language, where the Half-Cauchy distribution will be used (26). This statistical text is adequate for this Network meta-analysis because it considers positive means variances and their respective standard errors in the pre-post comparisons in the target randomized controlled trials. The Half-Cauchy test works addressing very high values for the tails into the distributions, thus, adding high rigor levels to consider variances in the extremes of the distributions and estimating the studies with high-variability in the posterior expectation as significantly heterogeneous at a 95% confidence interval (27). As outputs, the tau heterogeneity scores, the p-value of heterogeneity probabilities, and the corresponding confidence interval will be exposed (26). Data synthesis To analyze the pre-post differences between-studies doses of the two different types of exercise, a Network meta-analysis will be performed considering the variables “study”, “time of intervention (duration)”, the exercise “dose” defined by the resulting in METs-min/week, predefined by Ainsworth and colleagues (28), “pre-post mean differences”, “standard errors of the differences” and “effect sizes of the differences” where between-studies measurements are not consistent (26). To fix the bias regarding treatment duration, the dataset will be split into subgroups predefined by duration of the interventions within the present literature (i.e., between 8-10, 10-12, 12-14 a so on) to compare doses of interventions within the same duration range. Next, the prior probability will be addressed in the Bayesian model, considering objective information from the present dataset (means and standard deviations of the obtained sample), which will be the reference for the post-prior probability calculation (26). The Markov chain Monte Carlo simulation (MCMCS) will be used to estimate the probability of a random variable being different from the prior informed data (29). The deviance information criterion (DIC) will be calculated to identify if the Bayesian meta-analysis fits better into a fix or random effect distribution and thus, will determine if a fixed or a random network meta-analysis will be defined as the definitive model, as the lower is the DIC, the more fitted is the model (30). Trace and density plots will performed to check if the MCMCS is adequate for randomizing and homogenizing the data chains alongside all iterations of the post-prior probability calculation (31). In addition, the Potential Scale Reduction Factor (PSRF) for the MCMCS will be obtained through the statistics of Gelman-Rubin, considering a score between 1 and 1.05 to consider good convergence and probability sampling between chains within the posterior distribution (32). A network plot will be encoded to show the distances between the control group and different doses of the two exercise methods. The results of the prior-post probabilities comparison between the two exercise methods alongside different doses will be exposed in random forests and bar plots will expose the ranking of importance of each exercise type and respective dose (26). Subgroup analysis and sensitive analysis We will perform a subgroup analysis to compare the rate of improvement in physical fitness and BMD in postmenopausal women with osteoporosis. The analysis will consider the same Network Meta-Analysis encoding but be grouped by the factors “size” and “age” of the sample, high risk of bias (RoB) (26). In the case after evaluation, the quality of the studies is considered insufficient, these studies will be excluded to ensure the robustness and accuracy of the post-prior probabilities (26). Finally, a sensitivity analysis will be performed with leave-one-out cross-validation. For this purpose, the Network Meta-Analysis will , removing all studies and testing studies and testing iteratively rerun the results, testing all studies, and testing the model stability when excluding one study. If the remotion of some studies significantly reduces the T 2 and tau values, this study will be removed from the analysis to ensure the best robustness of the results (33). Patient and public involvement The design of this review protocol did not involve patients. Discussion In this systematic review and Network meta-analysis, we will evaluate the effects of MCT and HIIT on BMD and functional fitness of postmenopausal women with osteoporosis. Physical exercise is widely recognized as one of the main non-pharmacological interventions for individuals with osteoporosis (34). However, we have not found systematic reviews that compare the efficacy of these two physical exercise training methodologies in this specific context. Therefore, we have developed this protocol to systematically review and meta-analyze, with a Bayesian approach, the effectiveness of MCT and HIIT in women with osteoporosis, following the guidelines of the Cochrane Manual V.5.2.0, with the aim of providing solid evidence and more precise guidance for clinical practice (23). We hope to find robust findings about the benefits of the two methods physical exercise methods for the postmenopausal women with osteoporosis. Declarations Statements Ethical approval and consent to participate This study did not involve human participants, human data, human tissue, animals, or plants. Therefore, the need for ethical approval and consent to participate does not apply to this study. Ethics statement: Not applicable. Publication consent This manuscript does not include people's individual data (such as details, images, or videos). Therefore, publication consent is not applicable. Availability of data and materials The data used and analyzed during this study are available with the corresponding author upon reasonable request. All data supporting the findings of this study have been organized to ensure access, respecting privacy and confidentiality guidelines. Competing interests The authors declare that they have no competing financial or non-financial interests related to the content of this article. Funding This research did not receive specific financial support from funding agencies in the public, private, or non-profit sector. Authors contributions AMM: Conception, design of the study and data collection. AS: Data collection and manuscript writing. SE: Data collection, manuscript writing and interpretation. PF, TB, DM: Critical review and approval of the final manuscript. All authors read and approved the final version of the manuscript. Acknowledgements Not applicable References LeBoff MS, Greenspan SL, Insogna KL, Lewiecki EM, Saag KG, Singer AJ, et al. 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Database Filters PubMed/MEDLINE Data: 2014-2024 Article Type: RCT Species: Humans Language: English Other: Exclude preprints; MEDLINE Web of Science (WoS) Year of publication: 2014-2025 Document Types: Article Languages: English Document Types Exclude: Early Access or Proceeding Paper or Retracted Publication or Book Chapters or Data Paper Exclude – Sustainable Development Goals: 02 Zero Hunger or 04 Quality Education or 11 Sustainable Cities And Communities EBSCO Search modes: Search for all the search terms I have indicated Apply related words Apply equivalent subjects Restrict results: Full Text; Available References; Scientific Journals (Peer Reviewed) Publication date: 2014 – 2024 Publication type: Article Language: English Full Text PDF Cochrane Publication date: 01/01/2014 a 31/12/2024 Scopus Publication date: 2014-2025 Subjects Area (Excluded): Agricultural and Biological Sciences; Neuroscience; Psychology; Environmental Science; Engineering; Multidisciplinary; Computer Science; Pharmacology, Toxicology and Pharmaceutics; Immunology and Microbology; Chemistry; Chemical Engineering; Physics and Astronomy; Arts and Humanities; Materials Science; Business, Management and Accounting; Veterinary; Mathematics; Energy; Earth and Planetary Sciences; Dentistry; Economics, Econometrics and Finance; Decision Sciences Document Type: Article Language: English Keyword: Randomized Clinical Trial (RCT) CINAHL Full text Available references Publication date: January 2014 - December 2024 Reviewed by experts Publication type: Journal Article Language: English Expanders: Apply related words; Apply equivalent subjects Search mode: Find all my search terms SPORTDiscus Full text Available references Publication date: January 2014 - December 2024 Reviewed by experts Document type: Article Language: English Supplementary Files PRISMAPchecklist.docx PRISMA2020abstractchecklist.docx Cite Share Download PDF Status: Published Journal Publication published 04 Dec, 2025 Read the published version in Systematic Reviews → Version 1 posted Editorial decision: Minor revision 14 May, 2025 Reviewers agreed at journal 25 Apr, 2025 Reviewers invited by journal 18 Apr, 2025 Editor assigned by journal 20 Jan, 2025 First submitted to journal 20 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5456494","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":444726655,"identity":"d1a81b91-60b0-4d8c-af8c-f4e93bd73add","order_by":0,"name":"Miguel Monteiro","email":"","orcid":"","institution":"Polytechnic Institute of Bragança: Instituto Politecnico de Braganca","correspondingAuthor":false,"prefix":"","firstName":"Miguel","middleName":"","lastName":"Monteiro","suffix":""},{"id":444726656,"identity":"33fbb449-23f9-41a3-b38c-9ef347ac38c0","order_by":1,"name":"André 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Madrid","correspondingAuthor":false,"prefix":"","firstName":"Samuel","middleName":"","lastName":"Encarnação","suffix":""},{"id":444726658,"identity":"00015f34-cdc9-4cb5-b7d4-fb73296e5d09","order_by":3,"name":"Pedro Forte","email":"","orcid":"","institution":"ISCE DOURO: Instituto Superior de Ciencias Educativas do Douro","correspondingAuthor":false,"prefix":"","firstName":"Pedro","middleName":"","lastName":"Forte","suffix":""},{"id":444726659,"identity":"13cefbbf-6c96-47d0-bd09-6783611611da","order_by":4,"name":"Tiago Barbosa","email":"","orcid":"","institution":"Polytechnic Institute of Bragança: Instituto Politecnico de Braganca","correspondingAuthor":false,"prefix":"","firstName":"Tiago","middleName":"","lastName":"Barbosa","suffix":""},{"id":444726660,"identity":"ee76e907-6865-4758-bfce-00696b774e6e","order_by":5,"name":"Daniel Pecos Martín","email":"","orcid":"","institution":"Universidad de Alcala","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"Pecos","lastName":"Martín","suffix":""}],"badges":[],"createdAt":"2024-11-14 22:21:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5456494/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5456494/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13643-025-02899-9","type":"published","date":"2025-12-04T15:57:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82121454,"identity":"7d0ca353-2bea-4d8b-ad63-6765877ca1f5","added_by":"auto","created_at":"2025-05-07 03:23:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":851643,"visible":true,"origin":"","legend":"\u003cp\u003eSearch Strategies PubMed and Cochrane\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5456494/v1/86b6dcc7cb5ec078829ffc22.png"},{"id":97723902,"identity":"d392a499-8202-46fe-b42b-a29b379fa6c0","added_by":"auto","created_at":"2025-12-08 16:09:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1465096,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5456494/v1/ac8915e3-922e-40bf-b6fb-c3e2b7d71afd.pdf"},{"id":82122996,"identity":"deb11f6e-3a4a-40f5-b8b3-06b2db3bfec5","added_by":"auto","created_at":"2025-05-07 03:31:41","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":32775,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMAPchecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-5456494/v1/a663b3b0c87000af59004e9d.docx"},{"id":82121460,"identity":"85f03a71-9d38-441e-94bb-d80f4dcc7f5c","added_by":"auto","created_at":"2025-05-07 03:23:41","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":26749,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMA2020abstractchecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-5456494/v1/cf1e86232de88f3ba26c94c0.docx"}],"financialInterests":"","formattedTitle":"Impact of Multicomponent Physical Exercise and High Intensity Interval Training on Osteoporosis in Postmenopausal Women: protocol for a systematic review and Network meta-analysis of randomized controlled trials","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOsteoporosis is a condition defined by decreased bone density and degradation of bone microarchitecture, leading to increased fragility and susceptibility to fractures. The disease can affect various regions of the skeleton, being diagnosed and classified according to the degree of bone loss and history of previous fractures (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). With an estimated global prevalence of 200\u0026nbsp;million cases, osteoporosis constitutes a significant public health problem, with considerable economic repercussions (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Approximately 70% of cases occur in women in the postmenopausal phase (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOsteoporosis is a widely prevalent condition and is expected to increase in the coming years. It is estimated that about 30% of women in Europe and the United States have osteoporosis, and at least 40% of these women will suffer one or more fractures related to the disease in their lifetime. The consequences of this condition include a significant reduction in quality of life, compromising functional capacity, independence, and mobility. Additionally, osteoporosis represents a significant risk to life, as one in every three people dies within 12 months after a hip fracture (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe primary treatment for osteoporosis usually includes medications aimed at increasing BMD. However, exercises play an essential role in reducing other risk factors associated with falls and fractures, such as muscle weakness, loss of balance, and decreased functional capacity. In order for exercises to provide these benefits, it is crucial that they are correctly prescribed and that the patient maintains proper adherence to the program (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Regular physical activity can help minimize bone loss and reduce the frequency of falls and fractures (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough there are studies investigating the benefits of physical exercise for osteoporosis (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), there is a scarcity of specific research on the effects MCT and HIIT in treating osteoporosis in postmenopausal women. A comprehensive search in the literature revealed only two systematic reviews with this\u003c/p\u003e \u003cp\u003etype of intervention in the studied population. The first one analyzed the effects of HIIT on bone health, but presented limitations, such as consulting a restricted number of databases and the absence of meta-analyses (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The second review focused on MCT, but used mixed samples of middle-aged and older women, without conducting subgroup analyses by the participants\u0026rsquo; age (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Therefore, there is a clear need for studies that include complementary analyses and more robust search strategies, overcoming the limitations of previous works. In face of the limitations identified in previous studies, the need for more in-depth research using broader search strategies and complementary analyses is evident. Future investigations should focus on the role of MCT and HIIT in preventing fractures and improving bone health in postmenopausal women with osteoporosis. Furthermore, despite the importance of diagnostic methods such as dual-energy X-ray absorptiometry (DXA) and tools such as fracture risk assessment (FRAX), few studies analyze these parameters together in the context of physical exercise (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Therefore, more research is essential to clarify the effects of these interventions and provide a solid scientific basis for treatment and prevention strategies in postmenopausal women with osteoporosis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe protocol of this study followed the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) (11). The study protocol was prior registered at the International prospective register of systematic reviews (PROSPERO) under the registration number CRD42024604930.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligible criteria for study selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTypes of studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRCTs reviewed by peers and published in English language since the most relevant scientific literature is published in peer-reviewed journals which are written in English, thus ensuring greater scope and reliability for the study. Moreover, the search will encompass the last ten years of scientific literature (2014-2025) will be included in the search, . Grey literature was excluded, as the studies included in the academic repository could still not be peer-reviewed article. A wide collection of peer-reviewed studies is already available.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTypes of participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe eligible participants will be postmenopausal women diagnosed with a bone BMD T-score of less than or equal to -2.5. The inclusion criteria will be strictly limited to females, focusing exclusively on postmenopausal women. Studies with mixed populations of men and women will be excluded. However, there will be no restrictions regarding ethnicity, severity of symptoms, or disease duration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTypes of interventions and comparators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe will include treatments in which osteoporosis has been diagnosed based on BMD measured only with gold standard equipment i.e., DXA (12). The study compares the effects of two types of exercise interventions\u0026mdash;high-intensity interval training (HIIT) and multicomponent training (MCT)\u0026mdash;on this condition (13,14). Interventions must have a duration of at least 8 months. HIIT sessions involve alternating periods of high-intensity exercise, where the body works close to its maximum capacity (above 80% of maximum heart rate or 90% of the VO\u003csub\u003e2\u003c/sub\u003emax), with short periods of low-intensity recovery can involve rest or light active movement (below 50% of the maximum heart rate or below zones of 30-40% of \u0026nbsp;VO\u003csub\u003e2\u003c/sub\u003emax)(15). The HIIT exercises performed in the included studies can be characterized by multiple kinesiologic types: running (16), cycling (17), or circuit training (18) since they reach the required intensities of the HIIT method. \u0026nbsp; In contrast, MCT sessions refer to physical exercise interventions that incorporate two or moretypes of exercise, with common components including aerobic, resistance, and balance training commonly performed at moderate intensities (70% of maximum repetitions for strength, bellow 70% of the VO\u003csub\u003e2\u003c/sub\u003emax for aerobics and moderately challenging to balance exercises) (19).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTypes of outcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome will be the mean differences in bone mineral density (BMD), while the secondary outcome will focus on mean differences in physical fitness. Physical fitness will be assessed using standardized functional tests, such as the Short Physical Performance Battery (SPPB) (20), the Senior Fitness Test (21), and other similar assessments commonly reported in the literature, ensuring consistency and comparability of results across studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSearch strategies for the identification of studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eElectronic searches\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe search was updated to ensure that the final search date is as current as possible, and it was completed on January 18, 2025, guaranteeing the inclusion of the most recent and relevant studies. The following electronic databases were searched: PubMed/MEDLINE, Web of Science (WoS), EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, CINAHL, and SPORTDiscus. Specific search strategies validated for identifying randomized controlled trials (RCTs), such as those recommended in the Cochrane Handbook, were used as references to construct the queries. These strategies included Medical Subject Headings (MeSH) and equivalent terms, which were adapted and enriched for each database to ensure comprehensiveness. Detailed search strategies are presented in Figure 1. Filters were minimized to avoid the exclusion of relevant studies, focusing only on essential criteria, such as publication type (RCTs) and language (English), as outlined in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy selections\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe potentially relevant articles will be evaluated for eligibility through screening of titles and abstracts, and subsequently selected after a full-text review based on previously defined inclusion and exclusion criteria. The literature search and selection process will be initially conducted by two reviewers and then verified by a third author. Any disagreement will be resolved through discussion among the three authors. All studies will be managed and stored using Rayyan, an online platform tool for systematic review and meta-analysis (https://www.rayyan.ai/) (22), The reasons for excluding studies will be recorded and presented in a PRISMA flowchart.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData extraction and management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe relevant data from each study, including year of publication, sample size, participants\u0026apos; characteristics (e.g., age and T-score), and training modalities (type of exercise, frequency, and duration), will be extracted using a standardized and previously established Microsoft\u0026reg; Excel spreadsheet. Two reviewers will conduct The extraction process independently, and any discrepancies will be resolved through discussion or consultation with a third reviewer. All extracted data will be managed and analyzed in R Studio. Additional data will also be collected, such as intervention details, primary and secondary outcomes, and study design. where necessary, data transformations will be performed, including unit conversions, normalization, calculation of means or standard deviations, and effect sizes of treatments to ensure consistency across the study comparison (23). A sensitivity analysis will be conducted to evaluate the robustness of the results, accounting for factors such as sample size, high risk of bias 2 (RoB 2), missing data, and the analytical models used. Studies with low methodological quality after assessment will be excluded to maintain the reliability and validity of the findings (23). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCalibration exercises for study selection and data extraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCalibration exercises will be conducted before the formal study selection and data extraction processes to ensure consistency and accuracy among the reviewers. Two independent reviewers will screen a pilot set of 10 randomly selected articles, evaluating them against the inclusion and exclusion criteria. Discrepancies will be discussed and resolved in consultation with a third reviewer to refine the application of the criteria during the article screening. Similarly, for data extraction, the same prior-trained reviewers will independently extract data from five studies using a standardized extraction form. Any disagreements will be resolved through discussion or consultation with the third reviewer. These reading exercises will ensure that all reviewers are aligned and reduce variability in decision-making during the review process.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of RoB and quality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Cochrane Collaboration tool for assessing RoB 2 will be used to evaluate the RoB for randomized clinical trials (24). It contains five bias domains: bias due to the randomization process, deviation from intended intervention, missing outcome data, measurement of outcomes, selection of the reported result, and \u0026ldquo;overall risk of bias\u0026rdquo; judgment (25).\u003c/p\u003e\n\u003cp\u003eStudies with low methodological quality will be excluded based on the results of the risk of bias assessment using the Cochrane Risk of Bias Tool 2.0 (RoB 2.0). Low methodological quality will be defined as studies rated as \u0026ldquo;high risk of bias\u0026rdquo; in two or more of the five domains assessed by RoB 2.0, including bias arising from the randomization process, bias due to deviations from intended interventions, bias due to missing outcome data, bias in measurement of the outcome, and bias in selection of the reported result. Additionally, studies that lack essential methodological details required to make an informed judgment, even after contacting the authors for clarification, will also be classified as low quality. Consistent concerns about methodological integrity, such as unclear allocation concealment, incomplete outcome data, or selective outcome reporting, will further support the classification of low quality.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eManaging missing data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn case of missing, inadequate or confusing data, we will contact the corresponding author to request the essential information. If it is not possible to obtain this information, only the accessible data will be used in the analysis, with the limitations duly discussed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of heterogeneity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe between-studies heterogeneity (T2) assessment will be performed in R, programming language, where the Half-Cauchy distribution will be used (26). This statistical text is adequate for this Network meta-analysis because it considers positive means variances and their respective standard errors in the pre-post comparisons in the target randomized controlled trials. The Half-Cauchy test works addressing very high values for the tails into the distributions, thus, adding high rigor levels to consider variances in the extremes of the distributions and estimating the studies with high-variability in the posterior expectation as significantly heterogeneous at a 95% confidence interval (27). As outputs, the tau heterogeneity scores, the p-value of heterogeneity probabilities, and the corresponding confidence interval will be exposed (26).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData synthesis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo analyze the pre-post differences between-studies doses of the two different types of exercise, a Network meta-analysis will be performed considering the variables \u0026ldquo;study\u0026rdquo;, \u0026ldquo;time of intervention (duration)\u0026rdquo;, the exercise \u0026ldquo;dose\u0026rdquo; defined by the resulting in METs-min/week, predefined by Ainsworth and colleagues (28), \u0026ldquo;pre-post mean differences\u0026rdquo;, \u0026ldquo;standard errors of the differences\u0026rdquo; and \u0026ldquo;effect sizes of the differences\u0026rdquo; where between-studies measurements are not consistent \u0026nbsp;(26). To fix the bias regarding treatment duration, the dataset will be split into subgroups predefined by duration of the interventions within the present literature (i.e., between 8-10, 10-12, 12-14 a so on) to compare doses of interventions within the same duration range. Next, the prior probability will be addressed in the Bayesian model, considering objective information from the present dataset (means and standard deviations of the obtained sample), which will be the reference for the post-prior probability calculation (26). The Markov chain Monte Carlo simulation (MCMCS) will be used to estimate the probability of a random variable being different from the prior informed data (29). The deviance information criterion (DIC) will be calculated to identify if the Bayesian meta-analysis fits better into a fix or random effect distribution and thus, will determine if a fixed or a random network meta-analysis will be defined as the definitive model, as the lower is the DIC, the more fitted is the model (30). Trace and density plots will performed to check if the MCMCS is adequate for randomizing and homogenizing the data chains alongside all iterations of the post-prior probability calculation (31). In addition, the Potential Scale Reduction Factor (PSRF) for the MCMCS will be obtained through the statistics of Gelman-Rubin, considering a score between 1 and 1.05 to consider good convergence and probability sampling between chains within the posterior distribution (32). A network plot will be encoded to show the distances between the control group and different doses of the two exercise methods. The results of the prior-post probabilities comparison between the two exercise methods alongside different doses will be exposed in random forests and bar plots will expose the ranking of importance of each exercise type and respective dose (26).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup analysis and sensitive analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe will perform a subgroup analysis to compare the rate of improvement in physical fitness and BMD in postmenopausal women with osteoporosis. The analysis will consider the same Network Meta-Analysis encoding but be grouped by the factors \u0026ldquo;size\u0026rdquo; and \u0026ldquo;age\u0026rdquo; of the sample, high risk of bias (RoB) (26). In the case after evaluation, the quality of the studies is considered insufficient, these studies will be excluded to ensure the robustness and accuracy of the post-prior probabilities (26). Finally, a sensitivity analysis will be performed with leave-one-out cross-validation. For this purpose, the Network Meta-Analysis will , removing all studies and testing studies and testing iteratively rerun the results, testing all studies, and testing the model stability when excluding one study. If the remotion of some studies significantly reduces the \u003cem\u003eT\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e and tau values, this study will be removed from the analysis to ensure the best robustness of the results (33).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient and public involvement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe design of this review protocol did not involve patients.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this systematic review and Network meta-analysis, we will evaluate the effects of MCT and HIIT on BMD and functional fitness of postmenopausal women with osteoporosis. Physical exercise is widely recognized as one of the main non-pharmacological interventions for individuals with osteoporosis (34). However, we have not found systematic reviews that compare the efficacy of \u0026nbsp;these two physical exercise training methodologies in this specific context. Therefore, we have developed this protocol to systematically review and meta-analyze, with a Bayesian approach, the effectiveness of MCT and HIIT in women with osteoporosis, following the guidelines of the Cochrane Manual V.5.2.0, with the aim of providing solid evidence and more precise guidance for clinical practice (23). We hope to find robust findings about the benefits of the two methods physical exercise methods for the postmenopausal women with osteoporosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not involve human participants, human data, human tissue, animals, or plants. Therefore, the need for ethical approval and consent to participate does not apply to this study.\u003c/p\u003e\n\u003cp\u003eEthics statement: Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublication consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript does not include people\u0026apos;s individual data (such as details, images, or videos). Therefore, publication consent is not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used and analyzed during this study are available with the corresponding author upon reasonable request. All data supporting the findings of this study have been organized to ensure access, respecting privacy and confidentiality guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing financial or non-financial interests related to the content of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive specific financial support from funding agencies in the public, private, or non-profit sector.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAMM: Conception, design of the study and data collection.\u003c/p\u003e\n\u003cp\u003eAS: Data collection and manuscript writing.\u003c/p\u003e\n\u003cp\u003eSE: Data collection, manuscript writing and interpretation.\u003c/p\u003e\n\u003cp\u003ePF, TB, DM: Critical review and approval of the final manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eLeBoff MS, Greenspan SL, Insogna KL, Lewiecki EM, Saag KG, Singer AJ, et al. The clinician\u0026rsquo;s guide to prevention and treatment of osteoporosis. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2022 Oct;33(10):2049\u0026ndash;102.\u003c/li\u003e\n \u003cli\u003ePierini FS, Brom M, Scolnik M, Scaglioni V, Rosa JE, Soriano ER. Osteoporotic fractures in rheumatoid arthritis patients in Argentina: a matched retrospective cohort study. Adv Rheumatol Lond Engl. 2021 Apr 7;61(1):21.\u003c/li\u003e\n \u003cli\u003eWright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res Off J Am Soc Bone Miner Res. 2014 Nov;29(11):2520\u0026ndash;6.\u003c/li\u003e\n \u003cli\u003eRadominski SC, Bernardo W, Paula AP de, Albergaria B, Moreira C, Fernandes CE, et al. Diretrizes brasileiras para o diagn\u0026oacute;stico e tratamento da osteoporose em mulheres na p\u0026oacute;s‐menopausa. Rev Bras Reumatol. 2017 Jan 1;57:452\u0026ndash;66.\u003c/li\u003e\n \u003cli\u003eDaly RM, Via JD, Duckham RL, Fraser SF, Helge EW. Exercise for the prevention of osteoporosis in postmenopausal women: an evidence-based guide to the optimal prescription. Braz J Phys Ther. 2018 Nov 22;23(2):170.\u003c/li\u003e\n \u003cli\u003eBragonzoni L, Barone G, Benvenuti F, Canal V, Ripamonti C, Marini S, et al. A randomized clinical trial to evaluate the efficacy and safety of the ACTLIFE exercise program for women with post-menopausal osteoporosis: study protocol. Int J Environ Res Public Health [Internet]. 2020;17(3). Available from: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-02086329/full\u003c/li\u003e\n \u003cli\u003ePinheiro MB, Oliveira J, Bauman A, Fairhall N, Kwok W, Sherrington C. Evidence on physical activity and osteoporosis prevention for people aged 65+ years: a systematic review to inform the WHO guidelines on physical activity and sedentary behaviour. Int J Behav Nutr Phys Act. 2020 Nov 26;17(1):150.\u003c/li\u003e\n \u003cli\u003eSchapira D. Physical exercise in the prevention and treatment of osteoporosis: a review. J R Soc Med. 1988 Aug;81(8):461.\u003c/li\u003e\n \u003cli\u003eManaye S, Cheran K, Murthy C, Bornemann EA, Kamma HK, Alabbas M, et al. The Role of High-intensity and High-impact Exercises in Improving Bone Health in Postmenopausal Women: A Systematic Review. Cureus. 2023 Feb 5;15(2):e34644.\u003c/li\u003e\n \u003cli\u003eLinhares DG, Borba-Pinheiro CJ, de Castro JBP, dos Santos AOB, dos Santos LL, Cordeiro L de S, et al. Effects of Multicomponent Exercise Training on the Health of Older Women with Osteoporosis: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2022 Oct 30;19(21):14195.\u003c/li\u003e\n \u003cli\u003ePage MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLOS Med. 2021 Mar 29;18(3):e1003583.\u003c/li\u003e\n \u003cli\u003eKrugh M, Langaker MD. Dual-Energy X-Ray Absorptiometry. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Oct 29]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK519042/\u003c/li\u003e\n \u003cli\u003eBatacan RB, Duncan MJ, Dalbo VJ, Tucker PS, Fenning AS. Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies. Br J Sports Med. 2017 Mar 1;51(6):494\u0026ndash;503.\u003c/li\u003e\n \u003cli\u003eLabata-Lezaun N, Gonz\u0026aacute;lez-Rueda V, Llurda-Almuzara L, L\u0026oacute;pez-de-Celis C, Rodr\u0026iacute;guez-Sanz J, Bosch J, et al. Effectiveness of multicomponent training on physical performance in older adults: A systematic review and meta-analysis. Arch Gerontol Geriatr. 2023 Jan;104:104838.\u003c/li\u003e\n \u003cli\u003eACSM_CMS [Internet]. [cited 2024 Dec 17]. ACSM Blog. Available from: https://www.acsm.org/blog-detail\u003c/li\u003e\n \u003cli\u003eCostigan S, Eather N, Plotnikoff R, Taaffe D, Pollock E, Kennedy S, et al. Preliminary efficacy and feasibility of embedding high intensity interval training into the school day: a pilot randomized controlled trial. Prev Med Rep. 2015;2:973‐979.\u003c/li\u003e\n \u003cli\u003eMazurek K, Zmijewski P, Krawczyk K, Czajkowska A, Kęska A, Kapuściński P, et al. High intensity interval and moderate continuous cycle training in a physical education programme improves health-related fitness in young females. Biol Sport. 2016 Jun;33(2):139\u0026ndash;44.\u003c/li\u003e\n \u003cli\u003eBallesta-Garc\u0026iacute;a I, Mart\u0026iacute;nez-Gonz\u0026aacute;lez-Moro I, Ramos-Campo D, Carrasco-Poyatos M. High-Intensity Interval Circuit Training Versus Moderate-Intensity Continuous Training on Cardiorespiratory Fitness in Middle-Aged and Older Women: a Randomized Controlled Trial. Int J Environ Res Public Health [Internet]. 2020;17(5). Available from: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-02096551/full\u003c/li\u003e\n \u003cli\u003eACSM_CMS [Internet]. [cited 2024 Dec 17]. ACSM Blog. Available from: https://www.acsm.org/blog-detail\u003c/li\u003e\n \u003cli\u003ede F\u0026aacute;tima Ribeiro Silva C, Ohara DG, Matos AP, Pinto ACPN, Pegorari MS. Short Physical Performance Battery as a Measure of Physical Performance and Mortality Predictor in Older Adults: A Comprehensive Literature Review. Int J Environ Res Public Health. 2021 Oct 10;18(20):10612.\u003c/li\u003e\n \u003cli\u003eMason RC, Horvat M, Nocera J. The Effects of Exercise on the Physical Fitness of High and Moderate-Low Functioning Older Adult Women. J Aging Res. 2016;2016:8309284.\u003c/li\u003e\n \u003cli\u003eOuzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan\u0026mdash;a web and mobile app for systematic reviews. Syst Rev. 2016 Dec 5;5(1):210.\u003c/li\u003e\n \u003cli\u003eHiggins J, Thomas J. Cochrane Handbook for Systematic Reviews of Interventions [Internet]. 2022 [cited 2023 Jul 20]. Available from: https://training.cochrane.org/handbook/current\u003c/li\u003e\n \u003cli\u003eHiggins JPT, Altman DG, G\u0026oslash;tzsche PC, J\u0026uuml;ni P, Moher D, Oxman AD, et al. The Cochrane Collaboration\u0026rsquo;s tool for assessing risk of bias in randomised trials. BMJ. 2011 Oct 18;343:d5928.\u003c/li\u003e\n \u003cli\u003eNejadghaderi SA, Balibegloo M, Rezaei N. The Cochrane risk of bias assessment tool 2 (RoB 2) versus the original RoB: A perspective on the pros and cons. Health Sci Rep. 2024 Jun 3;7(6):e2165.\u003c/li\u003e\n \u003cli\u003eShim SR, Kim SJ, Lee J, R\u0026uuml;cker G. Network meta-analysis: application and practice using R software. Epidemiol Health. 2019 Jan 1;41:e2019013.\u003c/li\u003e\n \u003cli\u003eGelman A, Carlin JB, Stern HS, Dunson DB, Vehtari A, Rubin DB. Bayesian Data Analysis. 3rd ed. New York: Chapman and Hall/CRC; 2015. 675 p.\u003c/li\u003e\n \u003cli\u003eAinsworth BE, Haskell WL, Herrmann SD, Meckes N, Bassett DR, Tudor-Locke C, et al. 2011 Compendium of Physical Activities: a second update of codes and MET values. Med Sci Sports Exerc. 2011 Aug;43(8):1575\u0026ndash;81.\u003c/li\u003e\n \u003cli\u003eRaices Cruz I, Lindstr\u0026ouml;m J, Troffaes MCM, Sahlin U. Iterative importance sampling with Markov chain Monte Carlo sampling in robust Bayesian analysis. Comput Stat Data Anal. 2022 Dec 1;176:107558.\u003c/li\u003e\n \u003cli\u003eSpiegelhalter DJ, Best NG, Carlin BP, Van Der Linde A. Bayesian measures of model complexity and fit. J R Stat Soc Ser B Stat Methodol. 2002;64(4):583\u0026ndash;639.\u003c/li\u003e\n \u003cli\u003eLim D, Chen MH, Ibrahim JG, Kim S, Shah AK, Lin J. metapack: An R Package for Bayesian Meta-Analysis and Network Meta-Analysis with a Unified Formula Interface. R J. 2022 Dec 19;14(3):142.\u003c/li\u003e\n \u003cli\u003eBrooks SP, Gelman A. General Methods for Monitoring Convergence of Iterative Simulations. J Comput Graph Stat. 1998 Dec 1;7(4):434\u0026ndash;55.\u003c/li\u003e\n \u003cli\u003eViechtbauer W, Cheung MWL. Outlier and influence diagnostics for meta-analysis. Res Synth Methods. 2010 Apr;1(2):112\u0026ndash;25.\u003c/li\u003e\n \u003cli\u003eZhang L, Zheng YL, Wang R, Wang XQ, Zhang H. Exercise for osteoporosis: A literature review of pathology and mechanism. Front Immunol. 2022 Sep 9;13:1005665.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 2. Matching filters in each database.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eDatabase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eFilters\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003ePubMed/MEDLINE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cul\u003e\n \u003cli\u003eData: 2014-2024\u003c/li\u003e\n \u003cli\u003eArticle Type: RCT\u003c/li\u003e\n \u003cli\u003eSpecies: Humans\u003c/li\u003e\n \u003cli\u003eLanguage: English\u003c/li\u003e\n \u003cli\u003eOther: Exclude preprints; MEDLINE\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eWeb of Science (WoS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cul\u003e\n \u003cli\u003eYear of publication: 2014-2025\u003c/li\u003e\n \u003cli\u003eDocument Types: Article\u003c/li\u003e\n \u003cli\u003eLanguages: English\u003c/li\u003e\n \u003cli\u003eDocument Types Exclude: Early Access or Proceeding Paper or Retracted Publication or Book Chapters or Data Paper\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eExclude \u0026ndash; Sustainable Development Goals: 02 Zero Hunger or 04 Quality Education or 11 Sustainable Cities And Communities\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eEBSCO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cul\u003e\n \u003cli\u003eSearch modes: Search for all the search terms I have indicated\u003c/li\u003e\n \u003cli\u003eApply related words\u003c/li\u003e\n \u003cli\u003eApply equivalent subjects\u003c/li\u003e\n \u003cli\u003eRestrict results: Full Text; Available References; Scientific Journals (Peer Reviewed)\u003c/li\u003e\n \u003cli\u003ePublication date: 2014 \u0026ndash; 2024\u003c/li\u003e\n \u003cli\u003ePublication type: Article\u003c/li\u003e\n \u003cli\u003eLanguage: English\u003c/li\u003e\n \u003cli\u003eFull Text PDF\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eCochrane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cul\u003e\n \u003cli\u003ePublication date: 01/01/2014 a 31/12/2024\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eScopus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cul\u003e\n \u003cli\u003ePublication date: 2014-2025\u003c/li\u003e\n \u003cli\u003eSubjects Area (Excluded): Agricultural and Biological Sciences; Neuroscience; Psychology; Environmental Science; Engineering; Multidisciplinary; Computer Science; Pharmacology, Toxicology and Pharmaceutics; Immunology and Microbology; Chemistry; Chemical Engineering; Physics and Astronomy; Arts and Humanities; Materials Science; Business, Management and Accounting; Veterinary; Mathematics; Energy; Earth and Planetary Sciences; Dentistry; Economics, Econometrics and Finance; Decision Sciences\u003c/li\u003e\n \u003cli\u003eDocument Type: Article\u003c/li\u003e\n \u003cli\u003eLanguage: English\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKeyword: Randomized Clinical Trial (RCT)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eCINAHL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cul\u003e\n \u003cli\u003eFull text\u003c/li\u003e\n \u003cli\u003eAvailable references\u003c/li\u003e\n \u003cli\u003ePublication date: January 2014 - December 2024\u003c/li\u003e\n \u003cli\u003eReviewed by experts\u003c/li\u003e\n \u003cli\u003ePublication type: Journal Article\u003c/li\u003e\n \u003cli\u003eLanguage: English\u003c/li\u003e\n \u003cli\u003eExpanders: Apply related words; Apply equivalent subjects\u003c/li\u003e\n \u003cli\u003eSearch mode: Find all my search terms\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cp\u003eSPORTDiscus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50%;\"\u003e\n \u003cul\u003e\n \u003cli\u003eFull text\u003c/li\u003e\n \u003cli\u003eAvailable references\u003c/li\u003e\n \u003cli\u003ePublication date: January 2014 - December 2024\u003c/li\u003e\n \u003cli\u003eReviewed by experts\u003c/li\u003e\n \u003cli\u003eDocument type: Article\u003c/li\u003e\n \u003cli\u003eLanguage: English\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5456494/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5456494/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOsteoporosis is a progressive degenerative bone condition leading to increased fracture risk. Therefore, osteoporosis acknowledges around 200 million cases with about 70% of the cases occurring in postmenopausal women. Medicaments are often suggested to treat osteoporotic conditions; but physical exercise also plays an essential role. The current literature highlights multicomponent training (MCT) and high-intensity and high-impact exercises as physical exercise interventions that positively affect postmenopausal womens’ bone health. Furthermore, there is prior evidence of systematic reviews about the positive effects of both methods on the bone health of this population. Despite this prior evidence, no systematic reviews with metanalytic methods compare the effectiveness of the two interventions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods and analysis:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study will follow the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number (CRD42024604930). This systematic review and meta-analysis will include only Randomized controlled clinical trials (RCTs), which have verified the effects of one or both physical exercise methods in postmenopausal womens’ bone mineral density (BMD). The systematic search will be implemented at eight electronic databases, namely PubMed/MEDLINE, Web of Science (WoS), EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, CINAHL and SPORTDiscus will be used to retrieve the data of interest. The RCTs ' risk of bias (RoB) will be assessed with RoB 2 Cochrane tool, and between-study heterogeneity will be checked through the analysis of Half-Cauchy distribution. Additionally, a Network meta-analysis will be applied to to compare the between-studies dose-response in the patients’ bone health.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, we hope to find consistent results about the effects of MCT and HIIT in postmenopausal women with osteoporosis. Therefore, we also expect to observe between-intervention effects after the network meta-analysis approaches. This way, this study will significantly impact this field of knowledge.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics and dissemination:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe design of this review protocol did not involve patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePROSPERO registration number:\u003c/strong\u003e CRD42024604930.\u003c/p\u003e","manuscriptTitle":"Impact of Multicomponent Physical Exercise and High Intensity Interval Training on Osteoporosis in Postmenopausal Women: protocol for a systematic review and Network meta-analysis of randomized controlled trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 03:23:24","doi":"10.21203/rs.3.rs-5456494/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2025-05-14T08:04:16+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-04-25T08:35:13+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-18T07:40:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-21T04:56:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Systematic Reviews","date":"2025-01-20T17:48:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eeac082c-47db-469b-b868-b64fe990e591","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T16:02:23+00:00","versionOfRecord":{"articleIdentity":"rs-5456494","link":"https://doi.org/10.1186/s13643-025-02899-9","journal":{"identity":"systematic-reviews","isVorOnly":false,"title":"Systematic Reviews"},"publishedOn":"2025-12-04 15:57:58","publishedOnDateReadable":"December 4th, 2025"},"versionCreatedAt":"2025-05-07 03:23:24","video":"","vorDoi":"10.1186/s13643-025-02899-9","vorDoiUrl":"https://doi.org/10.1186/s13643-025-02899-9","workflowStages":[]},"version":"v1","identity":"rs-5456494","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5456494","identity":"rs-5456494","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}