{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:51:13Z","timestamp":1787010673899,"version":"build-2736575974"},"posted":{"date-parts":[[2025,8,29]]},"group-title":"Endocrinology (including Diabetes Mellitus and Metabolic Disease)","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Dual-energy x-ray absorptiometry (DXA)-derived areal bone mineral density (BMD) remains the clinical standard for assessing osteoporosis risk, yet it fails to identify over 75% of individuals who sustain fragility fractures. Direct in vivo mechanical assessment of cortical bone strength may address this diagnostic gap by capturing structural and material properties that govern whole-bone strength but are not reflected by BMD. We conducted a multicenter case-control study with cross-sectional assessment to compare ulna flexural rigidity, a biomechanical property correlated with whole-bone strength (R\u00b2 \u2248 0.99), estimated using Cortical Bone Mechanics Technology (CBMT), with DXA-derived BMD for discriminating prior fragility fractures in postmenopausal women. A total of 372 women aged 50\u201380 years (109 with low-trauma fractures, 263 matched controls) were enrolled across four U.S. sites. Ulna flexural rigidity was assessed by dynamic vibrational analysis; BMD was measured at the spine, hip, and 1\/3 radius. Women with prior fractures had significantly lower flexural rigidity than controls (absolute: 20.0 vs. 24.8 N\u00b7m\u00b2; 21% lower; weight-normalized: 0.29 vs. 0.36 N\u00b7m\u00b2\/kg; 22% lower; both P &lt; .001). CBMT demonstrated strong discriminatory accuracy (AUC = 0.80 normalized; 0.76 absolute) versus poor DXA performance (AUC \u2264 0.63) for discriminating all fragility fractures. In multivariable models including CBMT, DXA-derived BMD, age, and BMI, CBMT remained independently associated with fracture status, whereas BMD did not. Subgroup analyses showed CBMT retained strong performance in treatment-na\u00efve women (AUC = 0.85) and in those with non-osteoporotic BMD (AUC = 0.80). Exploratory fracture-site analyses demonstrated that ulna EI discriminated upper and lower extremity fractures, including hip, whereas DXA-derived BMD generally showed modest or nonsignificant discrimination. These findings demonstrate that in vivo mechanical assessment of cortical bone rigidity provides clinically relevant information beyond areal BMD, including women not classified high risk. Direct in vivo assessment of cortical bone rigidity may enhance fracture risk stratification and enhance osteoporosis screening.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Lay Summary<\/jats:title>\n                  <jats:p>Most people who break a bone from a simple fall do not meet the standard definition of osteoporosis based on a bone density scan (DXA). This means many at risk are not identified or treated. Our study tested a new, noninvasive technology that directly measures how strong a bone is by assessing how much it resists bending. We found that this measure, called flexural rigidity, more accurately identified women with past fractures than DXA did, even in women whose bone density was \u201cnormal\u201d. It also showed strong performance across different types of fractures, including hip fractures. Directly testing bone strength may help doctors better identify who needs treatment to prevent fractures.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:label>Graphical Abstract.<\/jats:label>\n                    <jats:caption>\n                      <jats:title>Summary of The STRONGER Study design, measurement principles, and discriminatory performance of CBMT-derived ulnar flexural rigidity and DXA-derived areal bone mineral density at standard clinical sites.<\/jats:title>\n                      <jats:p>\n                        <jats:bold>(Left)<\/jats:bold>\n                        Participant flow diagram for the STRONGER Study, a multicenter, case-control study, showing eligibility screening, adjudication, and final analytic sample (N = 372), including 109 postmenopausal women with prior fragility fractures and 263 matched controls.\n                        <jats:bold>(Center)<\/jats:bold>\n                        Conceptual schematics illustrating the measurement principles for Cortical Bone Mechanics Technology (CBMT) and dual-energy X-ray absorptiometry (DXA). The upper schematic depicts a simplified free-body diagram of a beam subjected to a mid-point load (\n                        <jats:italic>K<\/jats:italic>\n                        ) over length (\n                        <jats:italic>L<\/jats:italic>\n                        ), illustrating the Euler\u2013Bernoulli beam theory underlying CBMT-derived calculation of ulna flexural rigidity. The lower schematic illustrates the basic principle of DXA, which measures areal bone mineral density (BMD) based on differential X-ray attenuation (recreated from Luo, Y. (2017). Bone Imaging for Osteoporosis Assessment. In: Image-Based Multilevel Biomechanical Modeling for Fall-Induced Hip Fracture. Springer, Cham.\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/doi.org\/10.1007\/978-3-319-51671-4_3\">https:\/\/doi.org\/10.1007\/978-3-319-51671-4_3<\/jats:ext-link>\n                        ).\n                        <jats:bold>(Right)<\/jats:bold>\n                        Receiver operating characteristic (ROC) curves comparing the ability of CBMT-derived ulna flexural rigidity (absolute and weight-normalized) versus DXA-derived areal BMD at standard clinical sites to discriminate fracture status (all fractures). CBMT demonstrated substantially higher area under the curve (AUC) values (0.80) than any DXA site (\u22640.63), highlighting its potential to capture clinically meaningful aspects of bone strength not reflected by areal BMD alone. Notably, CBMT retained strong discriminatory performance in women with non-osteoporotic BMD and more effectively identified lower extremity and hip fractures (not shown), underscoring its potential to address a critical diagnostic gap including among women not classified as high risk by conventional thresholds.\n                      <\/jats:p>\n                    <\/jats:caption>\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"25334655v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.28.25334655","type":"posted-content","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:20:18Z","timestamp":1756513218000},"source":"Crossref","is-referenced-by-count":1,"title":["In Vivo Mechanical Assessment of Cortical Bone Rigidity Enhances Fracture Discrimination Beyond DXA in Postmenopausal Women"],"prefix":"10.64898","author":[{"given":"Brian C.","family":"Clark","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M.","family":"Manini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet E.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leatha A.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalampos","family":"Lyssikatos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6415-4936","authenticated-orcid":false,"given":"Stuart J.","family":"Warden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100608151074000_2025.08.28.25334655v2.1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.6.785"},{"key":"2025100608151074000_2025.08.28.25334655v2.2","unstructured":"Hansen D , Pelizzari P , Pyenson B . 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