Association of RC/HDL-C Ratio with Osteoporosis in Elderly Chinese Patients with MAFLD and Its Precursor States: A Cross-Sectional Study

Association of RC/HDL-C Ratio with Osteoporosis in Elderly Chinese Patients with MAFLD and Its Precursor States: A Cross-Sectional Study | 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 Association of RC/HDL-C Ratio with Osteoporosis in Elderly Chinese Patients with MAFLD and Its Precursor States: A Cross-Sectional Study Zhijun Li, Xiaoxia Jiang, Lei Li, Yeye Dai, Haiming Chen, Xunzhi Wang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9571175/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The association between the remnant cholesterol to high-density lipoprotein cholesterol ratio (RC/HDL-C) and osteoporosis in elderly patients with metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear, particularly across different metabolic subtypes. This study aimed to investigate the relationship between RC/HDL-C ratio and osteoporosis in elderly Chinese individuals with MAFLD and its precursor states. Methods This cross-sectional study included 71,140 elderly individuals (aged ≥65 years) with fatty liver disease from the Zhangjiagang National Health Information Platform (2024). Participants were categorized into four groups according to metabolic status: pre-MAFLD (simple hepatic steatosis, n=10,814), overweight/obese MAFLD (OW-MAFLD, n=29,210), lean MAFLD (Lean-MAFLD, n=10,521), and diabetic MAFLD (DM-MAFLD, n=20,595). Binary logistic regression with four stepwise-adjusted models was used to evaluate the association between RC/HDL-C ratio and osteoporosis. Restricted cubic spline (RCS) regression was performed to explore the dose–response relationship. Subgroup analyses and interaction tests were conducted to identify potential effect modifiers. Results Multivariable analysis showed that RC/HDL-C ratio was significantly and negatively associated with osteoporosis across all four subgroups (all P < 0.001). In the fully adjusted model, the strongest protective effect was observed in the OW-MAFLD group (OR = 0.664, 95% CI: 0.615–0.716), while the weakest effect was found in the DM-MAFLD group (OR = 0.788, 95% CI: 0.731–0.851). RCS analysis revealed a significant non-linear inverted U-shaped relationship between RC/HDL-C ratio and osteoporosis in all subgroups (all P for non-linearity < 0.001), with a protective threshold of approximately 0.4. Subgroup analyses showed that triglycerides modified the association in the pre-MAFLD, OW-MAFLD, and DM-MAFLD groups (P for interaction = 0.030, <0.001, and <0.001, respectively), with hypertriglyceridemia significantly attenuating the protective effect of RC/HDL-C ratio. Additionally, sex was identified as a significant effect modifier in the OW-MAFLD (P for interaction = 0.004) and DM-MAFLD (P for interaction = 0.008) groups, with a stronger protective effect observed in women than in men. Conclusions RC/HDL-C ratio serves as an independent protective factor against osteoporosis in elderly Chinese individuals with fatty liver disease. The protective effect is already present in the early stage (simple hepatic steatosis) but is significantly weakened in the presence of type 2 diabetes mellitus. A non-linear inverted U-shaped dose–response relationship with a protective threshold (approximately 0.4) exists between RC/HDL-C ratio and osteoporosis. Hypertriglyceridemia significantly attenuates the protective effect of RC/HDL-C ratio and represents a key factor to be addressed in bone health management in this population. Elderly Metabolic dysfunction-associated fatty liver disease RC/HDL-C ratio Osteoporosis Full Text Cite Share Download PDF Status: Posted Version 1 posted 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-9571175","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":635208940,"identity":"ea5841bb-4a4a-43b4-a083-cac1a697e69e","order_by":0,"name":"Zhijun Li","email":"","orcid":"","institution":"First People's Hospital of Zhangjiagang","correspondingAuthor":false,"prefix":"","firstName":"Zhijun","middleName":"","lastName":"Li","suffix":""},{"id":635208941,"identity":"2d54661f-c5fb-43dd-975c-c5133f741ec2","order_by":1,"name":"Xiaoxia Jiang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYBACxgYwJSHHz9584MCHH8RrsTCW7DmWeHBmD/GWVSRuuJFjfJiDjQi1zDNyzB7ztkkkzmzI+XCYgYdBnl/sAAGH9RxLN5zZJmHcz3B2w+ECCwbDmbMTCGhpbz4m8bFNQnZmY++GwzN4GBIMbhPS0swIdFWbBOOGwzwPDvOwEaMFaovihmM8DERqAfllxjkJYCCzGQADWYKwXwxBIcZTVifHL//48YcPP2zk+aUJaWlgYGNgRESHBH7lICDPANTC8IewwlEwCkbBKBjBAAAjsUh2wyD7IwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-2935-6265","institution":"Zhangjiagang center for disease control and prevention","correspondingAuthor":true,"prefix":"","firstName":"Xiaoxia","middleName":"","lastName":"Jiang","suffix":""},{"id":635208942,"identity":"54427267-f43a-49e4-bf0c-c02df2d33317","order_by":2,"name":"Lei Li","email":"","orcid":"","institution":"First People's Hospital of 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02:55:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9571175/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9571175/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109405626,"identity":"2a6f0a2b-e50f-49b4-bfac-bb287f69dfcf","added_by":"auto","created_at":"2026-05-17 13:19:25","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":406844,"visible":true,"origin":"","legend":"","description":"","filename":"manuscripHepatologyINT.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9571175/v1_covered_0f063f91-013d-4d0f-8374-32382be1c842.pdf"}],"financialInterests":"","formattedTitle":"Association of RC/HDL-C Ratio with Osteoporosis in Elderly Chinese Patients with MAFLD and Its Precursor States: A Cross-Sectional Study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Elderly, Metabolic dysfunction-associated fatty liver disease, RC/HDL-C ratio, Osteoporosis","lastPublishedDoi":"10.21203/rs.3.rs-9571175/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9571175/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eThe association between the remnant cholesterol to high-density lipoprotein cholesterol ratio (RC/HDL-C) and osteoporosis in elderly patients with metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear, particularly across different metabolic subtypes. This study aimed to investigate the relationship between RC/HDL-C ratio and osteoporosis in elderly Chinese individuals with MAFLD and its precursor states.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eThis cross-sectional study included 71,140 elderly individuals (aged ≥65 years) with fatty liver disease from the Zhangjiagang National Health Information Platform (2024). Participants were categorized into four groups according to metabolic status: pre-MAFLD (simple hepatic steatosis, n=10,814), overweight/obese MAFLD (OW-MAFLD, n=29,210), lean MAFLD (Lean-MAFLD, n=10,521), and diabetic MAFLD (DM-MAFLD, n=20,595). Binary logistic regression with four stepwise-adjusted models was used to evaluate the association between RC/HDL-C ratio and osteoporosis. Restricted cubic spline (RCS) regression was performed to explore the dose–response relationship. Subgroup analyses and interaction tests were conducted to identify potential effect modifiers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eMultivariable analysis showed that RC/HDL-C ratio was significantly and negatively associated with osteoporosis across all four subgroups (all P \u0026lt; 0.001). In the fully adjusted model, the strongest protective effect was observed in the OW-MAFLD group (OR = 0.664, 95% CI: 0.615–0.716), while the weakest effect was found in the DM-MAFLD group (OR = 0.788, 95% CI: 0.731–0.851). RCS analysis revealed a significant non-linear inverted U-shaped relationship between RC/HDL-C ratio and osteoporosis in all subgroups (all P for non-linearity \u0026lt; 0.001), with a protective threshold of approximately 0.4. Subgroup analyses showed that triglycerides modified the association in the pre-MAFLD, OW-MAFLD, and DM-MAFLD groups (P for interaction = 0.030, \u0026lt;0.001, and \u0026lt;0.001, respectively), with hypertriglyceridemia significantly attenuating the protective effect of RC/HDL-C ratio. Additionally, sex was identified as a significant effect modifier in the OW-MAFLD (P for interaction = 0.004) and DM-MAFLD (P for interaction = 0.008) groups, with a stronger protective effect observed in women than in men.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions \u003c/strong\u003eRC/HDL-C ratio serves as an independent protective factor against osteoporosis in elderly Chinese individuals with fatty liver disease. The protective effect is already present in the early stage (simple hepatic steatosis) but is significantly weakened in the presence of type 2 diabetes mellitus. A non-linear inverted U-shaped dose–response relationship with a protective threshold (approximately 0.4) exists between RC/HDL-C ratio and osteoporosis. Hypertriglyceridemia significantly attenuates the protective effect of RC/HDL-C ratio and represents a key factor to be addressed in bone health management in this population.\u003c/p\u003e","manuscriptTitle":"Association of RC/HDL-C Ratio with Osteoporosis in Elderly Chinese Patients with MAFLD and Its Precursor States: A Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-14 19:36:35","doi":"10.21203/rs.3.rs-9571175/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f9c3afcd-ae5b-4440-bae3-0838a5842537","owner":[],"postedDate":"May 14th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Reject","date":"2026-05-15T06:52:29+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2026-05-06T05:48:37+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-06T05:43:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-01T09:00:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Hepatology International","date":"2026-04-29T22:53:54+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T10:56:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-14 19:36:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9571175","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9571175","identity":"rs-9571175","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}