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Elevated Microdamage Spatially Correlates with Stress in Metastatic Vertebrae

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Abstract

Metastasis of cancer to the spine impacts bone quality. This study aims to characterize vertebral microdamage secondary to metastatic disease considering the pattern of damage and its relationship to stress and strain under load. Osteolytic and mixed osteolytic/osteoblastic vertebral metastases were produced in athymic rats via HeLa cervical or canine Ace-1 prostate cancer cell inoculation, respectively. After 21 days, excised motion segments (T12–L2) were µCT scanned, stained with BaSO4 and re-imaged. T13–L2 motion segments were loaded in axial compression to induce microdamage, re-stained and re-imaged. L1 (loaded) and T12 (unloaded) vertebrae were fixed, sample blocks cut, polished and BSE imaged. µFE models were generated of all L1 vertebrae with displacement boundary conditions applied based on the loaded µCT images. µCT stereological analysis, BSE analysis and µFE derived von Mises stress and principal strains were quantitatively compared (ANOVA), spatial correlations determined and patterns of microdamage assessed qualitatively. BaSO4 identified microdamage was found to be spatially correlated with regions of high stress in µFEA. Load-induced microdamage was shown to be elevated in the presence of osteolytic and mixed metastatic disease, with diffuse, crossed hatched areas of microdamage present in addition to linear microdamage and microfractures in metastatic tissue, suggesting diminished bone quality.

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Abbreviations

µCT:

Micro computed tomography

T12, L1:

12th thoracic and 1st lumbar vertebrae

N:

Newtons

SREs:

Skeletal related events

BaSO4 :

Barium sulfate

BSE imaging:

Backscatter electron imaging

µFE(A):

Micro finite element (analysis)

ANOVA:

Analysis of variance

RPMI:

Roswell Park Memorial Institute (RPMI) 1640 Medium

DMEM/F-12:

Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12

CO2 :

Carbon dioxide

TBV:

Trabecular bone volume

TMD:

Tissue mineral density

BMD:

Bone mineral density

TbN:

Trabecular number

TbS:

Trabecular spacing

TbTh:

Trabecular thickness

FHWM:

Full width half maximum

GLMax:

Grey level at the max intensity

GLAve:

Average grey level

GPa, MPa:

GigaPascal, MegaPascal

\(\varvec{\varepsilon}_{1}\) and \(\varvec{\varepsilon}_{3}\) :

Maximum and minimum principal strain

\(\varvec{\sigma}_{1}\) and \(\varvec{\sigma}_{3}\) :

Maximum and minimum principal stress

\(\varvec{\sigma}_{vm}\) :

Von Mises stress

SD:

Standard deviation

g(r):

Spatial correlation

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Authors and Affiliations

  1. Orthopaedics Biomechanics Laboratory, Sunnybrook Research Institute, Toronto, ON, Canada

    Ayelet Atkins, Mikhail Burke, Saeid Samiezadeh, Michael Hardisty & Cari M. Whyne

  2. Division of Orthopaedics, Department of Surgery, University of Toronto, Toronto, ON, Canada

    Margarete K. Akens & Cari M. Whyne

  3. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada

    Mikhail Burke & Cari M. Whyne

  4. Techna Institute, University Health Network, Toronto, ON, Canada

    Margarete K. Akens

  5. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    Margarete K. Akens

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  1. Ayelet Atkins
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  2. Mikhail Burke
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  3. Saeid Samiezadeh
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  4. Margarete K. Akens
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Correspondence to Cari M. Whyne.

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Associate Editor Sean S. Kohles oversaw the review of this article.

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Atkins, A., Burke, M., Samiezadeh, S. et al. Elevated Microdamage Spatially Correlates with Stress in Metastatic Vertebrae. Ann Biomed Eng 47, 980–989 (2019). https://doi.org/10.1007/s10439-018-02188-8

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