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Introductionmetastatic pathological fractures

Up to 27% of all cancers

Variable histology

Osteolytic & osteoblastic mix

Affected by bisphosphonate Rx

(not uniform)

Unknown biomechanics

Variable stereology

Bone mineral density

Bone volume fraction

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Aim

Quantify the comparative structural impactof..

Osteolytic lesions

Mixed osteolysis/osteoblastic lesions Bisphosphonate treatment

..on metastatic femoral lesions

Assess the reliability of clinical fracture risk

assessment.

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Controls

MT-1 humanbreast cancer

genes

MT-1 humanbreast cancer

genes

Canine Ace-1prostate cancer

genes

Healthy

N=6

Osteolytic

lesions

N=8

+ systemic

bisphosphonates

Osteolytic lesions

N=9

Mixed osteolytic/osteoblastic

lesions, N=9

5-6 week old

Nude athymic rats

N=32

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Stereology

CT imaging

Region of interest

600 slices distal physis

proximal CT slices per 0.01 mm

Each scan reconstructed

continuous tone (.ct) format greyscale bitmap (.bmp)

Amira Dev 5.2.2 imaging software

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Cortical destruction

>2/31/3-2/3

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0.5

0.55

0.6

0.65

0.7

0.75

0.8

0.85

Osteolytic BP-Osteolytic Mixed Control

TMD

gHA/cm3

ResultsTissue Mineral Density

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0.4

0.45

0.5

0.55

0.6

0.65

0.7

0.75

Osteolytic BP-Osteolytic Mixed Control

BV/TV

ResultsBone Volume Fraction, BV/TV

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0

20

40

60

80

100

120

140

160180

200

uc(MPa)

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

E

(GPa)

0

1

2

3

4

5

6

7

EA

(kN)

Ultimate Compressive Stress,

UC (Mpa)

Axial Rigidity,

EA, kN

Youngs Modulus,

E, GPa

ResultsMechanical Testing

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0

50

100

150

200

250

0.35 0.55 0.75 0.95

uc

(MPa)

TMD (gHA/cm3)

ResultsUC stress vs Tissue Mineral Density

R2=0.72

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Discussion

Bisphosphonate treatment increases

BV/TV by 19% (p

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Discussion

Mirels size correlates with bone volume fraction

Not with tissue mineral density

Ultimate compressive stress correlates Tissue mineral density

Not with bone volume

Mirels size does not correlate ultimate

compressive stress

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Discussion

CT improves

definition of cortical involvement

enhances reliability of Mirels score

Previous published inter-observer correlation

Size..0.48 0.56

Type.0.35 0.61

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Thank You