Purpose The mechanical competence of bone relies on both elastic stiffness and viscous damping; however, existing assessments have primarily involved stiffness quantification using bone mineral density but lack a collagen matrix-focused metric to predict fracture risk. 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. Methods 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 (pSHG) 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. Results Nanoindentation revealed a pronounced reduction in the long-term viscoelastic retardation time (<InlineEquation ID="IEq1"> <EquationSource Format="TEX">${\tau}_{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>τ</mi> <mn>2</mn> </msub> </math></EquationSource> </InlineEquation>) in diabetic bone; therefore, it can be considered a potential biomechanical indicator of matrix dysfunction. pSHG imaging demonstrated progressive collagen disorganization, attributed to weakened mineral–collagen interfacial coupling and reduced energy dissipation. Computational modeling demonstrated that <InlineEquation ID="IEq2"> <EquationSource Format="TEX">${\tau}_{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>τ</mi> <mn>2</mn> </msub> </math></EquationSource> </InlineEquation> reduction promotes crack propagation, compromising structural integrity. Conclusion These multimodal findings propose <InlineEquation ID="IEq3"> <EquationSource Format="TEX">${\tau}_{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>τ</mi> <mn>2</mn> </msub> </math></EquationSource> </InlineEquation> 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.

Collagen-Related Viscoelasticity as a Metric for Fracture Assessment in Cortical Bone

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2026年7月21日

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Jingxiao Zhong,
Jun Zhou,
Chie Watanabe,
Reina Tanaka,
Xiaoyuan Gu,
Boyang Wan,
Joo-Ri Kim-Kaneyama,
Yasutaka Sugamori,
Junning Chen,
Qing Li,
Yo Shibata

摘要

Purpose

The mechanical competence of bone relies on both elastic stiffness and viscous damping; however, existing assessments have primarily involved stiffness quantification using bone mineral density but lack a collagen matrix-focused metric to predict fracture risk. 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.

Methods

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 (pSHG) 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.

Results

Nanoindentation revealed a pronounced reduction in the long-term viscoelastic retardation time ( ${\tau}_{2}$ $τ_{2}$ ) in diabetic bone; therefore, it can be considered a potential biomechanical indicator of matrix dysfunction. pSHG imaging demonstrated progressive collagen disorganization, attributed to weakened mineral–collagen interfacial coupling and reduced energy dissipation. Computational modeling demonstrated that ${\tau}_{2}$ $τ_{2}$ reduction promotes crack propagation, compromising structural integrity.

Conclusion

These multimodal findings propose ${\tau}_{2}$ $τ_{2}$ 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.