Efficacy of Sigma Anti-bonding Molecule Calcium Carbonate on Bone Mineral Density

Efficacy of Sigma Anti-bonding Molecule Calcium Carbonate on Bone Mineral Density | 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 Efficacy of Sigma Anti-bonding Molecule Calcium Carbonate on Bone Mineral Density Donghoon Yoon, Alex Lee, Irawan Yusuf, Terawan Putranto, Lyana Setiawan7, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7061936/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Introduction. Osteoporosis is a long-term bone disease that causes a gradual loss of bone density and weakens its internal structure, increasing the risk of bone fractures. Prior preclinical studies have demonstrated that Sigma Anti-bonding Molecule Calcium Carbonate (SAC) exhibits beneficial effects on bone integrity in ovariectomized rat models. This clinical investigation evaluates the impact of SAC supplementation on bone mineral density(BMD) in an Asian cohort. Methods. A total of 82 participants were enrolled and stratified into three groups based on T-score: normal bone density (n=18), osteopenia (n=31), and osteoporosis (n=33). T-scores, BMD, and speed of sound (SOS) were measured at baseline and following approximately eight months of SAC intervention. All measurements were conducted at the distal radius, a clinically relevant site for assessing peripheral bone density. Results. After SAC administration, T-scores improved significantly (from -2.0 to -0.85, p <0.0001) along with increased BMD (from 0.95 to 1.10 g/cm², p <0.0001) across all age and gender groups. SAC treatment also significantly increased SOS values from 3,946 to 4,079 (p < 0.0001). Further, 65% of participants with osteopenia (20/31) improved to the normal group after treatment, while 64% of participants with osteoporosis (21/33) were reclassified into the osteopenia group. Remarkably, 12% of participants with baseline osteoporosis (4/33) transitioned into the normal bone density range. Discussion. Our findings suggest that SAC supplementation leads to significant improvements in bone health in Asian individuals, a population with higher susceptibility to osteoporosis. These results indicate that SAC could be a useful option to slow down age-related bone loss. Epidemiology Osteoporosis. Osteopenia Bone mineral density Sigma Anti-bonding Molecule Calcium Carbonate (SAC) Figures Figure 1 Figure 2 Figure 3 Full Text Additional Declarations The authors declare no competing interests. Supplementary Files SupplementalFigure1.png Supplemental Figure 1. Inverse relationship between age and bone health. A: T-score (p<0.0001), B: SOS (p<0.0001), C: BMD (p<0.0001) SupplementalFigure2.png Supplemental Figure 2. Efficacy of SAC by age groups. Efficacy of SAC was observed in all age groups. There is no significant difference in efficacy among age groups. A: T-score change p=0.324, B: SOS change p=0.114, and C: BMD change p=0.124. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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-7061936","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":482804251,"identity":"62d8b28b-ab76-4747-8e7d-d0ca22d170c8","order_by":0,"name":"Donghoon Yoon","email":"","orcid":"","institution":"University of Arkansas for Medical Science","correspondingAuthor":false,"prefix":"","firstName":"Donghoon","middleName":"","lastName":"Yoon","suffix":""},{"id":482804252,"identity":"5f603153-bded-453c-a215-b166e12e1a14","order_by":1,"name":"Alex Lee","email":"","orcid":"","institution":"Calcium and Bone Health Institute","correspondingAuthor":false,"prefix":"","firstName":"Alex","middleName":"","lastName":"Lee","suffix":""},{"id":482804253,"identity":"c22c7824-4886-4e76-874d-ac7f9037e161","order_by":2,"name":"Irawan Yusuf","email":"","orcid":"","institution":"Siloam Hospitals, Tangerang, Indonesia, \tMochtar Riady Institute for Nanotechnology, Faculty of Medicine Hasanuddin University","correspondingAuthor":false,"prefix":"","firstName":"Irawan","middleName":"","lastName":"Yusuf","suffix":""},{"id":482804254,"identity":"a3d22bc8-5138-4928-9ec7-b8321f22f948","order_by":3,"name":"Terawan Putranto","email":"","orcid":"","institution":"Central Army Hospital, Jakarta, Indonesia","correspondingAuthor":false,"prefix":"","firstName":"Terawan","middleName":"","lastName":"Putranto","suffix":""},{"id":482804255,"identity":"d625c9aa-81f4-4e59-a9cd-fcc78ca2ca0c","order_by":4,"name":"Lyana Setiawan7","email":"","orcid":"","institution":"Dharmais National Cancer Hospital, Jakarta, Indonesia.","correspondingAuthor":false,"prefix":"","firstName":"Lyana","middleName":"","lastName":"Setiawan7","suffix":""},{"id":482804256,"identity":"00eeb8e5-c3fc-48e0-8a83-f21d80cc54b1","order_by":5,"name":"Endang Hoyaranda","email":"","orcid":"","institution":"Prodia Group, Jakarta, Indonesia","correspondingAuthor":false,"prefix":"","firstName":"Endang","middleName":"","lastName":"Hoyaranda","suffix":""},{"id":482804257,"identity":"4f730b4e-4b29-40fd-9ac6-f1acbb93dc3a","order_by":6,"name":"Server Bozdogan","email":"","orcid":"","institution":"Advanced Calcium Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Server","middleName":"","lastName":"Bozdogan","suffix":""},{"id":482804258,"identity":"bd6ef6f8-406f-4930-94f9-f28d36513abb","order_by":7,"name":"J.W Saputro","email":"","orcid":"","institution":"Advanced Calcium Research Institute, Mersin, Turkyie.","correspondingAuthor":false,"prefix":"","firstName":"J.W","middleName":"","lastName":"Saputro","suffix":""},{"id":482804259,"identity":"e65f9136-3b56-49a8-80d1-76c18ef4265d","order_by":8,"name":"Jae Youl Cho","email":"","orcid":"","institution":"Sungkyunkwan University","correspondingAuthor":false,"prefix":"","firstName":"Jae","middleName":"Youl","lastName":"Cho","suffix":""},{"id":482804260,"identity":"2ceaa1ba-c4c1-4a43-afa9-cf1f15acb43f","order_by":9,"name":"Qian Zhou","email":"","orcid":"","institution":"Sanmen Juntong Orthopaedic and Traumatological Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Zhou","suffix":""},{"id":482804261,"identity":"e65e6a9f-5d21-4bc0-857c-436ee75d09a1","order_by":10,"name":"Sang Soo Lee","email":"","orcid":"","institution":"Hallym University","correspondingAuthor":false,"prefix":"","firstName":"Sang","middleName":"Soo","lastName":"Lee","suffix":""},{"id":482804262,"identity":"8bcc9c4e-b4dd-4e16-ae72-b6c68ec49d67","order_by":11,"name":"Jaehong Lee","email":"","orcid":"","institution":"Calcium and Bone Health Institute","correspondingAuthor":false,"prefix":"","firstName":"Jaehong","middleName":"","lastName":"Lee","suffix":""},{"id":482804263,"identity":"edbd9897-a673-4aa2-87aa-756a0dd495a4","order_by":12,"name":"Seong Hwan Roh","email":"","orcid":"","institution":"Calcium and Bone Health Institute","correspondingAuthor":false,"prefix":"","firstName":"Seong","middleName":"Hwan","lastName":"Roh","suffix":""},{"id":482804264,"identity":"407745a6-b762-491b-af85-edc37162c23a","order_by":13,"name":"Akira Kubo","email":"","orcid":"","institution":"Tokai University","correspondingAuthor":false,"prefix":"","firstName":"Akira","middleName":"","lastName":"Kubo","suffix":""},{"id":482804265,"identity":"3ff2bfaf-a6f4-44cd-9904-82b8e248218b","order_by":14,"name":"Paul K Lee","email":"","orcid":"","institution":"Calcium and Bone Health Institute","correspondingAuthor":false,"prefix":"","firstName":"Paul","middleName":"K","lastName":"Lee","suffix":""},{"id":482804266,"identity":"671df927-9be5-4e0e-b0fa-36b6265aa0c8","order_by":15,"name":"Jong Y. Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYBACxgYoQ4IdyKqwkSBFC88BBoYzaRISPERbJyGRANLCQFgLc3vv4ReMO+zyJWe+TnxwIMGizp6B+djHL/gc1nMuzYLxTLLlbOnczQYHEkAOY0ueLYNPy4wcMwPGNmYDOencbdIff4C08Bgz4wsFqJZ6AznJs9skILYQ1mL8gLHtsIG0BC9CC+MHvH45Y8aQeOa4gWQPxC+SPYfZkpnx6GAwbO8x/vBxR7WBxPGzG4EhVsfP3t58mPEHPi0NDGwSiQ3IQkArmPFFjjxQ/gM8CcCdi8+WUTAKRsEoGHEAACS1RzeW9neCAAAAAElFTkSuQmCC","orcid":"","institution":"Moffitt Cancer Center","correspondingAuthor":true,"prefix":"","firstName":"Jong","middleName":"Y.","lastName":"Park","suffix":""}],"badges":[],"createdAt":"2025-07-07 06:37:33","currentVersionCode":2,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7061936/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-7061936/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86972260,"identity":"29d89f48-d955-4e61-afaf-8c5bca346ab5","added_by":"auto","created_at":"2025-07-17 19:24:06","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":98377,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBaseline mean values of T-score, SOS, and BMD in clinical groups. A\u003c/strong\u003e: T-scores -0.11 (normal) vs -1.68 (osteopenia) vs. -3.34 (osteoporosis, p\u0026lt;0.0001). \u003cstrong\u003eB\u003c/strong\u003e: SOS (4,153 vs. 3,983 vs. 3,798, p\u0026lt;0.0001), and \u003cstrong\u003eC\u003c/strong\u003e: BMD (1.19, vs 1.00, vs. 0.80, p\u0026lt;0.0001). \u003cstrong\u003eD\u003c/strong\u003e. T score change after SAC treatment. Male and osteoporosis groups showed higher efficacy than female and other clinical groups (p\u0026lt;0.0001)\u003c/p\u003e","description":"","filename":"Figure120250711.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7061936/v2/5d2a2f6908e3c8d80eae4a5b.jpg"},{"id":86972262,"identity":"1c53d15b-900c-4081-a622-2469f4595449","added_by":"auto","created_at":"2025-07-17 19:24:06","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":64166,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of clinical group before and after treatment based on T-score. \u003c/strong\u003e65% of participants with osteopenia (20/31) were improved to the normal group after treatment,while 64% of participants with osteoporosis (21/33) became the osteopenia group. Notably, 12% of osteoporosis participants (4/33) improved to the normal range.\u003c/p\u003e","description":"","filename":"Figure220250712.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7061936/v2/4905968d1a98ad2888f74291.jpg"},{"id":86972439,"identity":"72ef4658-aa4b-4a0c-bb70-2ee3c9f28a09","added_by":"auto","created_at":"2025-07-17 19:32:08","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":88809,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProposed mechanism how SAC improves BMD. \u003c/strong\u003eDue to a weak intermolecular bonding of SAC with water molecules, forming Ca(H₂O)6, the SAC enables absorption into the bloodstream without vitamin D, staying bioavailable as ionized calcium. It elevates extracellular calcium in the bone microenvironment. These extracellular calcium and BMP-2 cooperatively promote the osteoblast differentiation/activity, increasing bone formation.\u003c/p\u003e","description":"","filename":"Figure3P20250712.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7061936/v2/5b569f962a0506e6490ce794.jpg"},{"id":86972757,"identity":"ac9c1e95-fdb0-4fdb-82f1-a02e4502479f","added_by":"auto","created_at":"2025-07-17 19:48:09","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1176945,"visible":true,"origin":"","legend":"","description":"","filename":"Osteoporosismanuscript20250713.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7061936/v2_covered_2701b6b4-9e2c-4697-8a31-19a078005c74.pdf"},{"id":86972684,"identity":"30b25bfc-d459-46e8-a93d-a5e08a15bf20","added_by":"auto","created_at":"2025-07-17 19:40:07","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":67640,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Figure 1. Inverse relationship between age and bone health\u003c/strong\u003e. A: T-score (p\u0026lt;0.0001), B: SOS (p\u0026lt;0.0001), C: BMD (p\u0026lt;0.0001)\u003c/p\u003e","description":"","filename":"SupplementalFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7061936/v2/c54a33b7eb5032f7bda6918d.png"},{"id":86972266,"identity":"b4ea36aa-df83-4290-80c7-b27d6f9513e0","added_by":"auto","created_at":"2025-07-17 19:24:06","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":58509,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Figure 2. Efficacy of SAC by age groups\u003c/strong\u003e. Efficacy of SAC was observed in all age groups. There is no significant difference in efficacy among age groups. A: T-score change p=0.324, B: SOS change p=0.114, and C: BMD change p=0.124.\u003c/p\u003e","description":"","filename":"SupplementalFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7061936/v2/b0ab2fa293ebd1a7bb4908de.png"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eEfficacy of Sigma Anti-bonding Molecule Calcium Carbonate on Bone Mineral Density\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Moffitt Cancer Center","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":"Osteoporosis. Osteopenia, Bone mineral density, Sigma Anti-bonding Molecule Calcium Carbonate (SAC)","lastPublishedDoi":"10.21203/rs.3.rs-7061936/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7061936/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction.\u003c/strong\u003e Osteoporosis is a long-term bone disease that causes a gradual loss of bone density and weakens its internal structure, increasing the risk of bone fractures. Prior preclinical studies have demonstrated that Sigma Anti-bonding Molecule Calcium Carbonate (SAC) exhibits beneficial effects on bone integrity in ovariectomized rat models. This clinical investigation evaluates the impact of SAC supplementation on bone mineral density(BMD) in an Asian cohort.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods.\u003c/strong\u003e A total of 82 participants were enrolled and stratified into three groups based on T-score: normal bone density (n=18), osteopenia (n=31), and osteoporosis (n=33). T-scores, BMD, and speed of sound (SOS) were measured at baseline and following approximately eight months of SAC intervention. All measurements were conducted at the distal radius, a clinically relevant site for assessing peripheral bone density.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults.\u003c/strong\u003e After SAC administration, T-scores improved significantly (from -2.0 to -0.85, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.0001) along with increased BMD (from 0.95 to 1.10 g/cm², \u003cem\u003ep\u003c/em\u003e\u0026lt;0.0001) across all age and gender groups. SAC treatment also significantly increased SOS values from 3,946 to 4,079 (p \u0026lt; 0.0001). Further, 65% of participants with osteopenia (20/31) improved to the normal group after treatment, while 64% of participants with osteoporosis (21/33) were reclassified into the osteopenia group. Remarkably, 12% of participants with baseline osteoporosis (4/33) transitioned into the normal bone density range.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion.\u003c/strong\u003e Our findings suggest that SAC supplementation leads to significant improvements in bone health in Asian individuals, a population with higher susceptibility to osteoporosis. These results indicate that SAC could be a useful option to slow down age-related bone loss.\u003c/p\u003e","manuscriptTitle":"Efficacy of Sigma Anti-bonding Molecule Calcium Carbonate on Bone Mineral Density","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2025-07-17 19:24:01","doi":"10.21203/rs.3.rs-7061936/v2","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}},{"code":1,"date":"2025-07-09 08:04:11","doi":"10.21203/rs.3.rs-7061936/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":"ffd73cca-d7d4-475a-bf2a-942529a79efc","owner":[],"postedDate":"July 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51448399,"name":"Epidemiology"}],"tags":[],"updatedAt":"2025-07-16T20:59:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-17 19:24:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-7061936","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7061936","identity":"rs-7061936","version":["v2"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}