Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice

Pendleton, Megan M.; Emerzian, Shannon R.; Sadoughi, Saghi; Li, Alfred; Liu, Jennifer W.; Tang, S. Y.; O’Connell, Grace D.; Sibonga, Jean D.; Alwood, Joshua S.; Keaveny, Tony M.

doi:10.1002/jbm4.10545

Cited by 6 publications

(2 citation statements)

References 88 publications

(198 reference statements)

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“…For example, non‐enzymatic collagen cross‐links known as AGEs, which form along the collagen backbone due to radiation‐induced oxidation, ( 63,64 ) are elevated in the irradiated bone in the current study and in other preclinical irradiation models. ( 37,68,69 ) However, the significant increase in AGEs was not associated with the observed reductions in vertebral strength. This is consistent with previous work in our lab ( 21 ) and others, ( 37,69 ) which demonstrated that AGEs do not accumulate at concentrations sufficient to alter bone mechanical properties.…”

Section: Discussionmentioning

confidence: 92%

Relative Effects of Radiation‐Induced Changes in Bone Mass, Structure, and Tissue Material on Vertebral Strength in a Rat Model

Emerzian

Vaidya

et al. 2023

J of Bone & Mineral Res

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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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Section: Discussionmentioning

confidence: 92%

Relative Effects of Radiation‐Induced Changes in Bone Mass, Structure, and Tissue Material on Vertebral Strength in a Rat Model

Emerzian

Vaidya

et al. 2023

J of Bone & Mineral Res

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“…Mouse micro-CT scans (Figure 1 ) were provided as a courtesy of Dr. Tony Keaveny of the University of California Berkeley, College of Engineering [ 13 ]. These scans were collected at the NASA Ames Research Center, and the collection was approved by the Institutional Animal Care and Use Committee under protocol #NAS‐13‐004‐Y3.…”

Section: Methodsmentioning

confidence: 99%

Rule and Neural Network-Based Image Segmentation of Mice Vertebrae Images

Madireddy¹,

Wu²

2022

Cureus

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BackgroundImage segmentation is a fundamental technique that allows researchers to process images from various sources into individual components for certain applications, such as visual or numerical evaluations. Image segmentation is beneficial when studying medical images for healthcare purposes. However, existing semantic image segmentation models like the U-net are computationally intensive. This work aimed to develop less complicated models that could still accurately segment images. MethodologyRule-based and linear layer neural network models were developed in Mathematica and trained on mouse vertebrae micro-computed tomography scans. These models were tasked with segmenting the cortical shell from the whole bone image. A U-net model was also set up for comparison. ResultsIt was found that the linear layer neural network had comparable accuracy to the U-net model in segmenting the mice vertebrae scans. ConclusionsThis work provides two separate models that allow for automated segmentation of mouse vertebral scans, which could be potentially valuable in applications such as pre-processing the murine vertebral scans for further evaluations of the effect of drug treatment on bone micro-architecture.

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Dose-dependent effects of gamma radiation sterilization on the collagen matrix of human cortical bone allograft and its influence on fatigue crack propagation resistance

Crocker,

Hering,

Akkus

et al. 2024

Cell Tissue Bank

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Fatigue crack propagation resistance and high-cycle S–N fatigue life of cortical bone allograft tissue are both negatively impacted in a radiation dose-dependent manner from 0 to 25 kGy. The standard radiation sterilization dose of 25–35 kGy has been shown to induce cleavage of collagen molecules into smaller peptides and accumulation of stable crosslinks within the collagen matrix, suggesting that these mechanisms may influence radiation-induced losses in cyclic fracture resistance. The objective of this study was to determine the radiation dose-dependency of collagen chain fragmentation and crosslink accumulation within the dose range of 0–25 kGy. Previously, cortical bone compact tension specimens from two donor femoral pairs were divided into four treatment groups (0 kGy, 10 kGy, 17.5 kGy, and 25 kGy) and underwent cyclic loading fatigue crack propagation testing. Following fatigue testing, collagen was isolated from one compact tension specimen in each treatment group from both donors. Radiation-induced collagen chain fragmentation was assessed using SDS-PAGE (n = 5), and accumulation of pentosidine, pyridinoline, and non-specific advanced glycation end products were assessed using a fluorometric assay (n = 4). Collagen chain fragmentation increased progressively in a dose-dependent manner (p < 0.001). Crosslink accumulation at all radiation dose levels increased relative to the 0 kGy control but did not demonstrate dose-dependency (p < 0.001). Taken together with our previous findings on fatigue crack propagation behavior, these data suggest that while collagen crosslink accumulation may contribute to reduced notched fatigue behavior with irradiation, dose-dependent losses in fatigue crack propagation resistance are mainly influenced by radiation-induced chain fragmentation.

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Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 6 publications

References 88 publications

Relative Effects of Radiation‐Induced Changes in Bone Mass, Structure, and Tissue Material on Vertebral Strength in a Rat Model

Relative Effects of Radiation‐Induced Changes in Bone Mass, Structure, and Tissue Material on Vertebral Strength in a Rat Model

Rule and Neural Network-Based Image Segmentation of Mice Vertebrae Images

Dose-dependent effects of gamma radiation sterilization on the collagen matrix of human cortical bone allograft and its influence on fatigue crack propagation resistance

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