Methods of skeletal age assessment using hand and wrist radiographs in children and their applicability across different ethnicities: systematic review and meta-analysis protocol

Methods of skeletal age assessment using hand and wrist radiographs in children and their applicability across different ethnicities: systematic review and meta-analysis protocol | 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 Methods of skeletal age assessment using hand and wrist radiographs in children and their applicability across different ethnicities: systematic review and meta-analysis protocol Sameera Wijayawardhana, Deepan Jayapala, Cree Gaskin, Jerrard Fernando, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5966121/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Skeletal age assessment using hand and wrist X-rays is commonly used to determine the biological maturity of children. It is invaluable when the chronological age is not known or in diagnosing and treating various endocrine, genetic, and developmental disorders as well as in a forensic context. Skeletal age is affected by both internal and external factors, leading to differences in skeletal maturity between children of different ethnicities. Regional studies have even questioned the applicability of current international skeletal age references across ethnicities. Methods A comprehensive literature search will be conducted utilising the PubMed, Scopus, Web of Science, EMBASE and Ovid online databases to identify existing publications. A combination of Medical Subject Headings (MeSH) terms and keywords, including “Skeletal age”, “bone age”, “radiograph”, and “hand”, will be used. Data screening and extraction will be done with Covidence software. Two independent reviewers will screen literature against predefined inclusion and exclusion criteria in abstract and full-text forms. A third reviewer will be consulted if consensus cannot be reached. The process will be reported in whole and presented in a PRISMA flow diagram. Study quality will be assessed by using the JBI critical appraisal tool. A meta-analysis will be conducted. Discussion This review will present a comprehensive analysis of existing literature on the applicability of skeletal age assessment methods using hand and wrist radiographs across different ethnicities. Further, this will be highlighting both strengths and gaps in existing knowledge. The inclusion of high-quality data will facilitate a quantitative meta-analysis for the exploration of ethnic differences in skeletal age assessments, ultimately laying the foundation for the development of population-specific reference standards. Systematic review registration: Submitted for registration in PROSPERO on 04.02.2025 Skeletal age Bone age Hand Radiographs X-ray Background Skeletal age resembles the level of biological and structural maturity of a child's skeletal system. ( 1 ) The skeletal system being a dynamic anatomical structure that undergoes growth and maturation evident on radiography, makes it a valuable tool for assessing a child's growth and maturation. Beyond its clinical significance in diagnosing and managing various endocrine, genetic, and developmental disorders in children, its analysis also contributes to various applications in forensic and anthropological contexts. ( 2 ) Skeletal age assessment based on the evaluation of epiphyseal ossification patterns and fusion of bones in the hand and wrist X-rays ( 3 , 4 ) is recognised as a reliable indicator of skeletal maturity in children. ( 2 , 4 ) Of the numerous methods of skeletal age assessment using hand radiographs, Gruelich and Pyle (GP) atlas and Tanner Whitehouse (TW) method are the widely used reference standards in clinical practice ( 5 ). The rate of ossification of an individual is affected by both extrinsic factors, such as environmental factors and socioeconomic status, and internal factors, such as genetics and illness. ( 6 , 7 ) Hence, a reference standard for one population might not necessarily be applicable to another population. The commonly used hand and wrist-based skeletal age assessment methods have been developed using cohorts of Caucasian children, raising concerns about their reliability and applicability in diverse populations. ( 8 , 9 ) In response, some countries have developed country-specific skeletal age reference standards ( 9 , 10 ), but no universally accepted method applies across different ethnicities. ( 5 ) This systematic review and meta-analysis aim to analyze the applicability of skeletal age assessment methods using hand and wrist X-rays among different ethnicities. Further, we aim to identify the various methods related to their anatomical bases, clinical applications, and applicability in healthy children, as described in the existing literature. This review will consolidate the current knowledge and address limitations in existing methodologies. Identifying these methods will ultimately facilitate the development of ethnicity-specific skeletal age assessment standards. Methods/ Design The proposed systematic review will be conducted complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. ( 10 ) It will follow the recommended standards for conducting and reporting systematic reviews. We consulted the International Prospective Register of Systematic Reviews (PROSPERO) ( https://www.crd.york.ac.uk/prospero/ ) to identify if there were ongoing protocols for systematic reviews similar to the present protocol. However, we found no relevant records as of February 2, 2024. This systematic review protocol is registered on PROSPERO and is reported according to the PRISMA-P 2015 checklist ( 11 ) (Supplementary File 1). Stage 1: Identifying the research question This review aims to explore the current literature pertaining to methods of skeletal age assessment using hand radiographs in healthy children. The primary objective of the review is to examine the methods of skeletal age assessment using hand and wrist radiographs in children and their applicability across different ethnicities. The specific objectives of the systematic review are as follows: To describe the methods of skeletal age assessment using hand radiographs applied across different ethnic populations To analyse the extent of ethnic variation in skeletal age development using hand radiographs and its implications for developing population-specific reference standards To describe the anatomical and physiological basis of methods used for skeletal age assessment based on hand radiographs in healthy children. Stage 2: Search strategy This systematic review will consider studies conducted prior to December 31, 2024. The review will include original descriptive observational studies, experimental studies and randomised controlled trials. Full-text original studies conducted among healthy children will be included without any language restrictions. Studies with inadequate data on ethnicity and studies involving children with pathological conditions will be excluded. In case more than one manuscript is published within the same study, the manuscript with the highest amount of precise information will be used. Table 1 summarises the inclusion and exclusion criteria developed. The corresponding authors will be contacted in the event of inadequate information reported in the article. The criteria might be adjusted during the screening after consensus among the reviewers. Any of the adjustments will be applied to all studies accordingly. Table 1 Inclusion and exclusion criteria Component Inclusion criteria Exclusion criteria Population (P) Healthy children of age < 18 years Children with pathological conditions affecting skeletal development. Intervention (I) Skeletal age assessment using hand and wrist radiographs. Studies have not used hand and wrist radiographs for skeletal age assessment. Comparison (C) Not mandatory. May include comparisons between different ethnicities or assessment methods Not applicable. Outcome (O) Method of skeletal age assessment and applicability of the technique across different ethnicities. Studies lacking data on skeletal age assessment methods or their applicability across ethnicities. Study Design Original descriptive observational studies, experimental studies, randomised controlled trials. Reviews, editorials, commentaries, case reports, and studies with inadequate data on ethnicity. Language and other There are no language restrictions. In cases of multiple publications from the same study, the one with less comprehensive data will be excluded. A comprehensive literature search will be conducted utilising the PubMed, Scopus, Web of Science, EMBASE and Ovid online databases to identify existing publications. The search strategy will use all identified keywords and index terms. A combination of Medical Subject Headings (MeSH) terms and keywords will be used to search across all fields. Keywords include “skeletal age”, “bone age”, “X-ray”, “radiograph”, and “hand” connected with Boolean operators. Additionally, the “Human” filter will be used. The search strategy is in Supplementary File 2. Stage 3: Study selection The final search results for screening will be exported into Covidence for duplicate removal. Titles and abstracts will be screened by two independent reviewers who are familiar with objectives, definitions and eligibility criteria. Any discrepancies will be resolved through discussion, and if a consensus cannot be reached, a third reviewer will be consulted. The data extraction sheets will be pilot-tested using five randomly selected studies. To refine the inclusion and exclusion criteria, an assessment will be conducted once 10% of the studies have been screened by both reviewers to determine whether redefining the requirements is necessary. Studies that are filtered through screening will be retrieved in full-text form. Reviewers will read the full text to further filter against eligibility criteria. The process will be reported as a whole and presented in a PRISMA flow diagram. Study quality will be assessed by using JBI critical appraisal tools. ( 12 ) Stage 4: Data extraction, Analysis and Reporting A minimum of two independent reviewers will conduct data extraction. The data extraction variables are listed under study characteristics, population characteristics, methodological characteristics, outcome, limitations and recommendations. (Supplementary file 3). The Covidence software will be further utilised for data extraction. Once the selection process is over, the team will carry out a pilot data extraction to look into the necessary adjustments in the extraction template. The meta-analysis will be conducted using a metafor package in R. We will compute standardised mean differences (SMDs) or other relevant effect size measures to quantify the ethnic differences in skeletal age in each assigned sex at birth. A random-effects model will be employed to account for between-study variability, considering the potential heterogeneity in the studies included. We will assess the magnitude of ethnic variability using the I² statistic and conduct subgroup analyses to explore potential moderating variables. Publication bias will be evaluated through visual inspection of funnel plots and formal tests such as Egger's test. Sensitivity analyses will be conducted to assess the stability of our results and to explore the influence of high-quality studies on the overall findings. This review will use the following definitions: “Chronological age” – The time that has passed since the birth of an individual “Skeletal age” - The age expressed in years that corresponds to the level of maturation of bones “Methods of assessment” - A specific technique or procedure for determining a child’s skeletal age, typically by interpretation of hand radiographs compared against established reference standards “Hand X-rays” - Radiographic images of the hand and wrist, commonly used in skeletal age assessment since carpal bones show distinct and measurable changes, allowing for skeletal age assessment “Healthy children” - Children who are free from conditions or diseases that could impact normal bone growth and development, ensuring their growth reflects the typical growth pattern of the related population. Discussion This will be the first systematic review to evaluate the applicability of skeletal age assessment methods using hand and wrist radiographs across different ethnicities. By incorporating a wide range of study designs, including observational, experimental, and randomised controlled trials (RCTs), the review will provide a comprehensive analysis of existing evidence. The inclusion of high-quality data will facilitate a quantitative synthesis using meta-regression, which will allow for a robust exploration of ethnic differences in skeletal age assessments. By comparing various assessment methods, this review aims to determine their applicability across diverse populations, ultimately laying the foundation for the development of population-specific reference standards. Abbreviations JBI Joanna Biggs Institute Declarations Ethics approval and consent to participate: Not applicable. Consent for publication : Not applicable. Availability of data and materials: Not applicable Competing interests: The authors declare that they have no competing interests. Funding: Not applicable Authors' contributions: SW developed the study protocol in collaboration with DJ, CG, JF, YM and PW. SW, YM, and PW formulated the draft search strategy. All authors read and approved the final manuscript. Acknowledgements: Not Applicable Authors' information : Dr Sameera Wijayawardhana (ORCID: 0000-0002-5725-8235) Department of Anatomy, Faculty of Medicine, University of Kelaniya, Sri Lanka Email: [email protected] Dr Deepan Jayapala (ORCID: 0000-0003-3960-6029) Department of Anatomy, Faculty of Medicine, University of Moratuwa, Sri Lanka Email: [email protected] Professor Cree Gaskin – (ORCID: 0000-0001-9447-9427) Department of Radiology and Medical Imaging, University of Virginia, United States Email: [email protected] Dr Jerrard Fernando (ORCID: 0000-0003-2282-0555) Lady Ridgway Hospital for Children, Colombo, Sri Lanka Email: [email protected] Dr Yasith Mathagasinghe (ORCID: 0000-0003-4641-5642) Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia Email: [email protected] Professor Pujitha Wickramasinghe (ORCID: 0000-0002-8355-1283) Department of Paediatrics, Faculty of Medicine, University of Colombo, Sri Lanka Email: [email protected] References Lazar L, Phillip M. Pubertal Disorders and Bone Maturation. Endocrinology and Metabolism Clinics of North America. 2012;41(4):805-25. Cavallo F, Mohn A, Chiarelli F, Giannini C. Evaluation of Bone Age in Children: A Mini-Review. Front Pediatr. 2021;9:580314. Mohammed RB, Reddy MA, Jain M, Singh JR, Sanghvi P, Thetay AA. Digital radiographic evaluation of hand-wrist bone maturation and prediction of age in South Indian adolescents. Hand (N Y). 2014;9(3):375-83. De Sanctis V, Di Maio S, Soliman AT, Raiola G, Elalaily R, Millimaggi G. Hand X-ray in pediatric endocrinology: Skeletal age assessment and beyond. Indian J Endocrinol Metab. 2014;18(Suppl 1):S63-71. Manzoor Mughal A, Hassan N, Ahmed A. Bone age assessment methods: a critical review. Pak J Med Sci. 2014;30(1):211-5. Tristán Fernández JM, Ruiz Santiago F, Pérez de la Cruz A, Lobo Tanner G, Aguilar Cordero MJ, Collado Torreblanca F. [The influence of nutrition and social environment on the bone maturation of children]. Nutr Hosp. 2007;22(4):417-24. Cardoso HF. Environmental effects on skeletal versus dental development: Using a documented subadult skeletal sample to test a basic assumption in human osteological research. Am J Phys Anthropol. 2007;132(2):223-33. Büken B, Şafak AA, Büken E, Yazıcı B, Erkol ZZ, Erzengin ÖU. Is the Tanner–Whitehouse (TW3) method sufficiently reliable for forensic age determination of Turkish children?*. Turkish Journal of Medical Sciences. 2010. Tiwari PK, Nayak AK, Verma A, Pandey SK, Mishra A, Devadas D, et al. Greulich and Pyle atlas: a non-reliable skeletal maturity assessment method in the North Indian population. Forensic Sci Med Pathol. 2024;20(1):106-16. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Bmj. 2021;372:n71. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1. Aromataris E LC, Porritt K, Pilla B, Jordan Z, editors. JBI Manual for Evidence Synthesis. JBI https://synthesismanual.jbi.global. https://doi.org/10.46658/JBIMES-24-012024 [ Supplementary Files Supplementaryfile1.docx Supplementaryfile2.docx Supplementaryfile3.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 22 Sep, 2025 Reviewers agreed at journal 03 Sep, 2025 Reviewers invited by journal 03 Sep, 2025 Editor assigned by journal 28 Mar, 2025 First submitted to journal 05 Feb, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5966121","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":509541565,"identity":"ba79ccf3-7dbd-4297-a1b4-cb1968e593a9","order_by":0,"name":"Sameera Wijayawardhana","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYDADfh7mBjCDj4dYLZI9jBAtbERrMThDrBb59tOJDz7usUvcfOZg2wOGGjuglgOEDM/dbDjjWXLitrON7QYMx5IZ2HgbCGhhyN0mzXOAOXfbecY2CQa2Awxs/IQc1v92++8/B+pzN/eDtPwjQgvDjdxtzAwHDudu4G1sk2BsO0CEw2683SzZc+B4/Qyg9yUS+5J5CHpfvj9344cfB6qN+XuSj0l8+GYnx8+TQMhlyAComOiIHAWjYBSMglGABwAA7A9CGeqqIewAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-5725-8235","institution":"University of Kelaniya Faculty of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Sameera","middleName":"","lastName":"Wijayawardhana","suffix":""},{"id":509541566,"identity":"96448f5f-1290-4876-af5c-f6c14a188afd","order_by":1,"name":"Deepan Jayapala","email":"","orcid":"","institution":"University of Moratuwa","correspondingAuthor":false,"prefix":"","firstName":"Deepan","middleName":"","lastName":"Jayapala","suffix":""},{"id":509541567,"identity":"a9d22fc7-5719-4fef-8188-24c496a1b3a1","order_by":2,"name":"Cree Gaskin","email":"","orcid":"","institution":"University of Virginia","correspondingAuthor":false,"prefix":"","firstName":"Cree","middleName":"","lastName":"Gaskin","suffix":""},{"id":509541568,"identity":"daea7d79-82f8-4704-b810-df1e8844c446","order_by":3,"name":"Jerrard Fernando","email":"","orcid":"","institution":"Lady Ridgeway Hospital for Children","correspondingAuthor":false,"prefix":"","firstName":"Jerrard","middleName":"","lastName":"Fernando","suffix":""},{"id":509541569,"identity":"0ab0ee4d-e03b-4149-a1b8-a1b7fe2b8290","order_by":4,"name":"Yasith Mathagasinghe","email":"","orcid":"","institution":"Monash University","correspondingAuthor":false,"prefix":"","firstName":"Yasith","middleName":"","lastName":"Mathagasinghe","suffix":""},{"id":509541570,"identity":"cebcced2-43b0-481d-9e10-1dbfc4a264b7","order_by":5,"name":"Pujitha Wickramasinghe","email":"","orcid":"","institution":"University of Colombo Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Pujitha","middleName":"","lastName":"Wickramasinghe","suffix":""}],"badges":[],"createdAt":"2025-02-05 13:34:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5966121/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5966121/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90886993,"identity":"97253cfa-e376-4b48-a366-3feb7811c67c","added_by":"auto","created_at":"2025-09-09 10:17:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":570986,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5966121/v1/a1224db6-75c6-41ea-835f-d58061c8a7c4.pdf"},{"id":90886441,"identity":"16f314b2-acfa-4430-91f4-b4275f2b36d8","added_by":"auto","created_at":"2025-09-09 10:09:24","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":35834,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5966121/v1/4592eeedad69efffbd8e5fdb.docx"},{"id":90886437,"identity":"0742f7d2-3c55-4173-88f4-65f4a962828b","added_by":"auto","created_at":"2025-09-09 10:09:24","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":13460,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile2.docx","url":"https://assets-eu.researchsquare.com/files/rs-5966121/v1/43783e2002c14bea86f21746.docx"},{"id":90886989,"identity":"4415c565-f799-4378-a500-b04f9659dd8c","added_by":"auto","created_at":"2025-09-09 10:17:24","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":15611,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile3.docx","url":"https://assets-eu.researchsquare.com/files/rs-5966121/v1/679c38788d0c67ab93b5c1c3.docx"}],"financialInterests":"","formattedTitle":"Methods of skeletal age assessment using hand and wrist radiographs in children and their applicability across different ethnicities: systematic review and meta-analysis protocol","fulltext":[{"header":"Background","content":"\u003cp\u003eSkeletal age resembles the level of biological and structural maturity of a child's skeletal system. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) The skeletal system being a dynamic anatomical structure that undergoes growth and maturation evident on radiography, makes it a valuable tool for assessing a child's growth and maturation. Beyond its clinical significance in diagnosing and managing various endocrine, genetic, and developmental disorders in children, its analysis also contributes to various applications in forensic and anthropological contexts. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eSkeletal age assessment based on the evaluation of epiphyseal ossification patterns and fusion of bones in the hand and wrist X-rays (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) is recognised as a reliable indicator of skeletal maturity in children. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Of the numerous methods of skeletal age assessment using hand radiographs, Gruelich and Pyle (GP) atlas and Tanner Whitehouse (TW) method are the widely used reference standards in clinical practice (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The rate of ossification of an individual is affected by both extrinsic factors, such as environmental factors and socioeconomic status, and internal factors, such as genetics and illness. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Hence, a reference standard for one population might not necessarily be applicable to another population. The commonly used hand and wrist-based skeletal age assessment methods have been developed using cohorts of Caucasian children, raising concerns about their reliability and applicability in diverse populations. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) In response, some countries have developed country-specific skeletal age reference standards (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), but no universally accepted method applies across different ethnicities. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eThis systematic review and meta-analysis aim to analyze the applicability of skeletal age assessment methods using hand and wrist X-rays among different ethnicities. Further, we aim to identify the various methods related to their anatomical bases, clinical applications, and applicability in healthy children, as described in the existing literature. This review will consolidate the current knowledge and address limitations in existing methodologies. Identifying these methods will ultimately facilitate the development of ethnicity-specific skeletal age assessment standards.\u003c/p\u003e"},{"header":"Methods/ Design","content":"\u003cp\u003eThe proposed systematic review will be conducted complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) It will follow the recommended standards for conducting and reporting systematic reviews. We consulted the International Prospective Register of Systematic Reviews (PROSPERO) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.crd.york.ac.uk/prospero/\u003c/span\u003e\u003cspan address=\"https://www.crd.york.ac.uk/prospero/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) to identify if there were ongoing protocols for systematic reviews similar to the present protocol. However, we found no relevant records as of February 2, 2024. This systematic review protocol is registered on PROSPERO and is reported according to the PRISMA-P 2015 checklist (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) (Supplementary File 1).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStage 1: Identifying the research question\u003c/h2\u003e\u003cp\u003eThis review aims to explore the current literature pertaining to methods of skeletal age assessment using hand radiographs in healthy children. The primary objective of the review is to examine the methods of skeletal age assessment using hand and wrist radiographs in children and their applicability across different ethnicities.\u003c/p\u003e\u003cp\u003eThe specific objectives of the systematic review are as follows:\u003c/p\u003e\u003cp\u003e\u003col style=\"list-style-type:lower-alpha;\"\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eTo describe the methods of skeletal age assessment using hand radiographs applied across different ethnic populations\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eTo analyse the extent of ethnic variation in skeletal age development using hand radiographs and its implications for developing population-specific reference standards\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eTo describe the anatomical and physiological basis of methods used for skeletal age assessment based on hand radiographs in healthy children.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStage 2: Search strategy\u003c/h3\u003e\n\u003cp\u003eThis systematic review will consider studies conducted prior to December 31, 2024. The review will include original descriptive observational studies, experimental studies and randomised controlled trials. Full-text original studies conducted among healthy children will be included without any language restrictions. Studies with inadequate data on ethnicity and studies involving children with pathological conditions will be excluded. In case more than one manuscript is published within the same study, the manuscript with the highest amount of precise information will be used. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarises the inclusion and exclusion criteria developed. The corresponding authors will be contacted in the event of inadequate information reported in the article. The criteria might be adjusted during the screening after consensus among the reviewers. Any of the adjustments will be applied to all studies accordingly.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eInclusion and exclusion criteria\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComponent\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInclusion criteria\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExclusion criteria\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePopulation (P)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHealthy children of age\u0026thinsp;\u0026lt;\u0026thinsp;18 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eChildren with pathological conditions affecting skeletal development.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntervention (I)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSkeletal age assessment using hand and wrist radiographs.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStudies have not used hand and wrist radiographs for skeletal age assessment.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComparison (C)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNot mandatory.\u003c/p\u003e\u003cp\u003eMay include comparisons between different ethnicities or assessment methods\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcome (O)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMethod of skeletal age assessment and applicability of the technique across different ethnicities.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStudies lacking data on skeletal age assessment methods or their applicability across ethnicities.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy Design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOriginal descriptive observational studies, experimental studies, randomised controlled trials.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eReviews, editorials, commentaries, case reports, and studies with inadequate data on ethnicity.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLanguage and other\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThere are no language restrictions.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIn cases of multiple publications from the same study, the one with less comprehensive data will be excluded.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA comprehensive literature search will be conducted utilising the PubMed, Scopus, Web of Science, EMBASE and Ovid online databases to identify existing publications. The search strategy will use all identified keywords and index terms. A combination of Medical Subject Headings (MeSH) terms and keywords will be used to search across all fields. Keywords include \u0026ldquo;skeletal age\u0026rdquo;, \u0026ldquo;bone age\u0026rdquo;, \u0026ldquo;X-ray\u0026rdquo;, \u0026ldquo;radiograph\u0026rdquo;, and \u0026ldquo;hand\u0026rdquo; connected with Boolean operators. Additionally, the \u0026ldquo;Human\u0026rdquo; filter will be used. The search strategy is in Supplementary File 2.\u003c/p\u003e\n\u003ch3\u003eStage 3: Study selection\u003c/h3\u003e\n\u003cp\u003eThe final search results for screening will be exported into Covidence for duplicate removal. Titles and abstracts will be screened by two independent reviewers who are familiar with objectives, definitions and eligibility criteria. Any discrepancies will be resolved through discussion, and if a consensus cannot be reached, a third reviewer will be consulted. The data extraction sheets will be pilot-tested using five randomly selected studies. To refine the inclusion and exclusion criteria, an assessment will be conducted once 10% of the studies have been screened by both reviewers to determine whether redefining the requirements is necessary. Studies that are filtered through screening will be retrieved in full-text form. Reviewers will read the full text to further filter against eligibility criteria. The process will be reported as a whole and presented in a PRISMA flow diagram. Study quality will be assessed by using JBI critical appraisal tools. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e\n\u003ch3\u003eStage 4: Data extraction, Analysis and Reporting\u003c/h3\u003e\n\u003cp\u003eA minimum of two independent reviewers will conduct data extraction. The data extraction variables are listed under study characteristics, population characteristics, methodological characteristics, outcome, limitations and recommendations. (Supplementary file 3). The Covidence software will be further utilised for data extraction. Once the selection process is over, the team will carry out a pilot data extraction to look into the necessary adjustments in the extraction template. The meta-analysis will be conducted using a metafor package in R. We will compute standardised mean differences (SMDs) or other relevant effect size measures to quantify the ethnic differences in skeletal age in each assigned sex at birth. A random-effects model will be employed to account for between-study variability, considering the potential heterogeneity in the studies included. We will assess the magnitude of ethnic variability using the I\u0026sup2; statistic and conduct subgroup analyses to explore potential moderating variables. Publication bias will be evaluated through visual inspection of funnel plots and formal tests such as Egger's test. Sensitivity analyses will be conducted to assess the stability of our results and to explore the influence of high-quality studies on the overall findings.\u003c/p\u003e\u003cp\u003eThis review will use the following definitions:\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026ldquo;Chronological age\u0026rdquo; \u0026ndash;\u003c/b\u003e The time that has passed since the birth of an individual\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026ldquo;Skeletal age\u0026rdquo; -\u003c/b\u003e The age expressed in years that corresponds to the level of maturation of bones\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026ldquo;Methods of assessment\u0026rdquo; -\u003c/b\u003e A specific technique or procedure for determining a child\u0026rsquo;s skeletal age, typically by interpretation of hand radiographs compared against established reference standards\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026ldquo;Hand X-rays\u0026rdquo; -\u003c/b\u003e Radiographic images of the hand and wrist, commonly used in skeletal age assessment since carpal bones show distinct and measurable changes, allowing for skeletal age assessment\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026ldquo;Healthy children\u0026rdquo; -\u003c/b\u003e Children who are free from conditions or diseases that could impact normal bone growth and development, ensuring their growth reflects the typical growth pattern of the related population.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis will be the first systematic review to evaluate the applicability of skeletal age assessment methods using hand and wrist radiographs across different ethnicities. By incorporating a wide range of study designs, including observational, experimental, and randomised controlled trials (RCTs), the review will provide a comprehensive analysis of existing evidence. The inclusion of high-quality data will facilitate a quantitative synthesis using meta-regression, which will allow for a robust exploration of ethnic differences in skeletal age assessments. By comparing various assessment methods, this review aims to determine their applicability across diverse populations, ultimately laying the foundation for the development of population-specific reference standards.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eJBI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eJoanna Biggs Institute\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eNot applicable\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eSW developed the study protocol in collaboration with DJ, CG, JF, YM and PW. SW, YM, and PW formulated the draft search strategy. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information :\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr Sameera Wijayawardhana \u0026nbsp;(ORCID: 0000-0002-5725-8235)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDepartment of Anatomy, Faculty of Medicine, University of Kelaniya, Sri Lanka\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u003c/p\u003e\n\u003cp\u003eDr Deepan Jayapala \u0026nbsp;(ORCID: 0000-0003-3960-6029)\u003c/p\u003e\n\u003cp\u003eDepartment of Anatomy, Faculty of Medicine, University of Moratuwa, Sri Lanka\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProfessor Cree Gaskin \u0026ndash; (ORCID: \u0026nbsp; 0000-0001-9447-9427)\u003c/p\u003e\n\u003cp\u003eDepartment of Radiology and Medical Imaging, University of Virginia, United States\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDr Jerrard Fernando \u0026nbsp;(ORCID: 0000-0003-2282-0555)\u003c/p\u003e\n\u003cp\u003eLady Ridgway Hospital for Children, Colombo, Sri Lanka\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDr Yasith Mathagasinghe \u0026nbsp;(ORCID: 0000-0003-4641-5642)\u003c/p\u003e\n\u003cp\u003eDepartment of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProfessor Pujitha Wickramasinghe \u0026nbsp;(ORCID: 0000-0002-8355-1283)\u003c/p\u003e\n\u003cp\u003eDepartment of Paediatrics, Faculty of Medicine, University of Colombo, Sri Lanka\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLazar L, Phillip M. Pubertal Disorders and Bone Maturation. Endocrinology and Metabolism Clinics of North America. 2012;41(4):805-25.\u003c/li\u003e\n\u003cli\u003eCavallo F, Mohn A, Chiarelli F, Giannini C. Evaluation of Bone Age in Children: A Mini-Review. Front Pediatr. 2021;9:580314.\u003c/li\u003e\n\u003cli\u003eMohammed RB, Reddy MA, Jain M, Singh JR, Sanghvi P, Thetay AA. Digital radiographic evaluation of hand-wrist bone maturation and prediction of age in South Indian adolescents. Hand (N Y). 2014;9(3):375-83.\u003c/li\u003e\n\u003cli\u003eDe Sanctis V, Di Maio S, Soliman AT, Raiola G, Elalaily R, Millimaggi G. Hand X-ray in pediatric endocrinology: Skeletal age assessment and beyond. Indian J Endocrinol Metab. 2014;18(Suppl 1):S63-71.\u003c/li\u003e\n\u003cli\u003eManzoor Mughal A, Hassan N, Ahmed A. Bone age assessment methods: a critical review. Pak J Med Sci. 2014;30(1):211-5.\u003c/li\u003e\n\u003cli\u003eTrist\u0026aacute;n Fern\u0026aacute;ndez JM, Ruiz Santiago F, P\u0026eacute;rez de la Cruz A, Lobo Tanner G, Aguilar Cordero MJ, Collado Torreblanca F. [The influence of nutrition and social environment on the bone maturation of children]. Nutr Hosp. 2007;22(4):417-24.\u003c/li\u003e\n\u003cli\u003eCardoso HF. Environmental effects on skeletal versus dental development: Using a documented subadult skeletal sample to test a basic assumption in human osteological research. Am J Phys Anthropol. 2007;132(2):223-33.\u003c/li\u003e\n\u003cli\u003eB\u0026uuml;ken B, Şafak AA, B\u0026uuml;ken E, Yazıcı B, Erkol ZZ, Erzengin \u0026Ouml;U. Is the Tanner\u0026ndash;Whitehouse (TW3) method sufficiently reliable for forensic age determination of Turkish children?*. Turkish Journal of Medical Sciences. 2010.\u003c/li\u003e\n\u003cli\u003eTiwari PK, Nayak AK, Verma A, Pandey SK, Mishra A, Devadas D, et al. Greulich and Pyle atlas: a non-reliable skeletal maturity assessment method in the North Indian population. Forensic Sci Med Pathol. 2024;20(1):106-16.\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. Bmj. 2021;372:n71.\u003c/li\u003e\n\u003cli\u003eMoher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1.\u003c/li\u003e\n\u003cli\u003eAromataris E LC, Porritt K, Pilla B, Jordan Z, editors. JBI Manual for Evidence Synthesis. JBI https://synthesismanual.jbi.global. https://doi.org/10.46658/JBIMES-24-012024 [\u003c/li\u003e\n\u003c/ol\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":"Skeletal age, Bone age, Hand, Radiographs, X-ray","lastPublishedDoi":"10.21203/rs.3.rs-5966121/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5966121/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\u003eSkeletal age assessment using hand and wrist X-rays is commonly used to determine the biological maturity of children. It is invaluable when the chronological age is not known or in diagnosing and treating various endocrine, genetic, and developmental disorders as well as in a forensic context. Skeletal age is affected by both internal and external factors, leading to differences in skeletal maturity between children of different ethnicities. Regional studies have even questioned the applicability of current international skeletal age references across ethnicities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA comprehensive literature search will be conducted utilising the PubMed, Scopus, Web of Science, EMBASE and Ovid online databases to identify existing publications. A combination of Medical Subject Headings (MeSH) terms and keywords, including “Skeletal age”, “bone age”, “radiograph”, and “hand”, will be used.\u003c/p\u003e\n\u003cp\u003eData screening and extraction will be done with Covidence software. Two independent reviewers will screen literature against predefined inclusion and exclusion criteria in abstract and full-text forms. A third reviewer will be consulted if consensus cannot be reached. The process will be reported in whole and presented in a PRISMA flow diagram. Study quality will be assessed by using the JBI critical appraisal tool. A meta-analysis will be conducted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis review will present a comprehensive analysis of existing literature on the applicability of skeletal age assessment methods using hand and wrist radiographs across different ethnicities. Further, this will be highlighting both strengths and gaps in existing knowledge. The inclusion of high-quality data will facilitate a quantitative meta-analysis for the exploration of ethnic differences in skeletal age assessments, ultimately laying the foundation for the development of population-specific reference standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSystematic review registration: \u003c/strong\u003eSubmitted for registration in PROSPERO on 04.02.2025\u003c/p\u003e","manuscriptTitle":"Methods of skeletal age assessment using hand and wrist radiographs in children and their applicability across different ethnicities: systematic review and meta-analysis protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 10:09:20","doi":"10.21203/rs.3.rs-5966121/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-09-22T07:10:45+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-09-03T09:49:00+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-03T08:26:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-28T19:33:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"Systematic Reviews","date":"2025-02-05T08:33:39+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":"48a8d8b2-51ad-42c2-b693-0ba621dc5b01","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T14:46:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 10:09:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5966121","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5966121","identity":"rs-5966121","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}