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This study introduces an experimentally anchored, time-resolved analysis framework for quantifying cortical bone matrix viscoelasticity and evaluating fracture susceptibility arising from collagen organization defects. It further proposes a collagen-related viscoelasticity metric for bone assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using murine diabetic femoral cortical bone specimens, a time-resolved viscoelastic analysis based on nanoindentation-based creep testing was performed to quantify cortical bone matrix behavior. Polarization-resolved second-harmonic generation (\n                      <jats:italic>p<\/jats:italic>\n                      SHG) microscopy was employed to characterize collagen alignment and orientation at the ultrastructural level. Finite-element simulations incorporating experimentally derived viscoelastic parameters were used to evaluate crack propagation behavior and fracture susceptibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nanoindentation revealed a pronounced reduction in the long-term viscoelastic retardation time (\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$${\\tau}_{2}$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:msub>\n                              <mml:mi>\u03c4<\/mml:mi>\n                              <mml:mn>2<\/mml:mn>\n                            <\/mml:msub>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      ) in diabetic bone; therefore, it can be considered a potential biomechanical indicator of matrix dysfunction.\n                      <jats:italic>p<\/jats:italic>\n                      SHG imaging demonstrated progressive collagen disorganization, attributed to weakened mineral\u2013collagen interfacial coupling and reduced energy dissipation. Computational modeling demonstrated that\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$${\\tau}_{2}$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:msub>\n                              <mml:mi>\u03c4<\/mml:mi>\n                              <mml:mn>2<\/mml:mn>\n                            <\/mml:msub>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      reduction promotes crack propagation, compromising structural integrity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These multimodal findings propose\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$${\\tau}_{2}$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:msub>\n                              <mml:mi>\u03c4<\/mml:mi>\n                              <mml:mn>2<\/mml:mn>\n                            <\/mml:msub>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      as a quantitative, informative, collagen-related viscoelastic metric linking collagen degradation and ultrastructure to fracture susceptibility. This study provides the foundation for the development of strategies for next-generation bone collagen assessment, which complement densitometry-centric assessment, particularly in metabolic disorders like diabetes, where mineral changes alone are insufficient to predict fracture risks.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10439-026-04280-w","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T12:53:31Z","timestamp":1784638411000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Collagen-Related Viscoelasticity as a Metric for Fracture Assessment in Cortical Bone"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6380-0641","authenticated-orcid":false,"given":"Jingxiao","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo-Ri","family":"Kim-Kaneyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Sugamori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junning","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1876-3298","authenticated-orcid":false,"given":"Yo","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"4280_CR1","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1016\/S0140-6736(02)08657-9","volume":"359","author":"SR Cummings","year":"2002","unstructured":"Cummings, S. 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