The observed increased risk of fracture after cancer radiation therapy is presumably due to a radiation‐induced reduction in whole‐bone strength. However, the mechanisms for impaired strength remain unclear, as the increased fracture risk is not fully explained by changes in bone mass. To provide insight, a small animal model was used to determine how much of this whole‐bone weakening effect for the spine is attributable to changes in bone mass, structure, and material properties of the bone tissue and their relative effects. Further, because women have a greater risk of fracture after radiation therapy than men, we investigated if sex had a significant influence on bone's response to irradiation. Fractionated in vivo irradiation (10 × 3 Gy) or sham irradiation (0 Gy) was administered daily to the lumbar spine in twenty‐seven 17‐week‐old Sprague–Dawley rats (n = 6–7/sex/group). Twelve weeks after final treatment, animals were euthanized, and lumbar vertebrae (L4 and L5) were isolated. Using a combination of biomechanical testing, micro‐CT‐based finite element analysis, and statistical regression analysis, we separated out the effect of mass, structural, and tissue material changes on vertebral strength. Compared with the sham group (mean ± SD strength = 420 ± 88 N), the mean strength of the irradiated group was lower by 28% (117 N/420 N, p < 0.0001). Overall, the response of treatment did not differ with sex. By combining results from both general linear regression and finite element analyses, we calculated that mean changes in bone mass, structure, and material properties of the bone tissue accounted for 56% (66 N/117 N), 20% (23 N/117 N), and 24% (28 N/117 N), respectively, of the overall change in strength. As such, these results provide insight into why an elevated clinical fracture risk for patients undergoing radiation therapy is not well explained by changes in bone mass alone. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Study Design. Micro-computed tomography-(micro-CT-) based finite element analysis of cadaveric human lumbar vertebrae virtually implanted with total disc arthroplasty (TDA) implants. Objective. (1) Assess the relationship between vertebral porosity and maximum levels of bone-tissue stress following TDA; (2) determine whether the implant's loading mode (axial compression vs. sagittal bending) alters the relationship between vertebral porosity and bone-tissue stress. Summary of Background Data. Implant subsidence may be related to the bone biomechanics in the underlying vertebral body, which are poorly understood. For example, it remains unclear how the stresses that develop in the supporting bone tissue depend on the implant's loading mode or on typical interindividual variations in vertebral morphology. Methods. Data from micro-CT scans from 12 human lumbar vertebrae (8 males, 4 females; 51-89 years of age; bone volume fraction [BV/TV] ¼ 0.060-0.145) were used to construct highresolution finite element models (37 mm element edge length) comprising disc-vertebra-implant motion segments. Implants were loaded to 800 N of force in axial compression, flexion-, and extension-induced impingement. For comparison, the same net loads were applied via an intact disc without an implant. Linear regression was used to assess the relationship between BV/TV, loading mode, and the specimen-specific change in stress caused by implantation.Results. The increase in maximum bone-tissue stress caused by implantation depended on loading mode (P < 0.001), increasing more in bending-induced impingement than axial compression (for the same applied force). The change in maximum stress was significantly associated with BV/TV (P ¼ 0.002): higher porosity vertebrae experienced a disproportionate increase in stress compared with lower porosity vertebrae. There was a significant interaction between loading mode and BV/TV (P ¼ 0.002), indicating that loading mode altered the relationship between BV/TV and the change in maximum bone-tissue stress. Conclusion. Typically-sized TDA implants disproportionately increase the bone-tissue stress in more porous vertebrae; this affect is accentuated when the implant impinges in sagittal bending.