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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT Tissue Biomechanics Philippe K. Zysset Institute for Lightweight Design and Structural Biomechanics Vienna University of Technology, Austria http://www.ilsb.tuwien.ac.at Einf¨ uhrung in die Biomedizinische Technik, Wien den 9. Oktober 2009 TU Wien Ph. Zysset

Biomechanik Gewebe

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Page 1: Biomechanik Gewebe

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Tissue Biomechanics

Philippe K. Zysset

Institute for Lightweight Design and Structural BiomechanicsVienna University of Technology, Austriahttp://www.ilsb.tuwien.ac.at

Einfuhrung in die Biomedizinische Technik, Wien den 9. Oktober 2009

TU Wien Ph. Zysset

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Outline

1 Introduction

2 MCF, Lamella & BSU

3 Tissue

4 µCT

5 pQCT

6 HR-QCT

TU Wien Ph. Zysset

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Outline

1 Introduction

2 MCF, Lamella & BSU

3 Tissue

4 µCT

5 pQCT

6 HR-QCT

TU Wien Ph. Zysset

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

The Bone Syndrome

TU Wien Ph. Zysset

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Motivation

Metabolic bone diseases

Fractures

Implant fixation

The three ages of a woman (G. Klimt)

TU Wien Ph. Zysset

I d i MCF L ll & BSU Ti CT QCT HR QCT

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Osteoporosis

FACTS IN AUSTRIA

750’000 patients

1 out of 3 women

1 out of 7 men12’000 hip fx a year

Chronic pain and impair.

20% mortality after 70

12’000 Euros per hip fxKoeck et al., Wiener Klin Wochen,

2001.

Hip fracture

TU Wien Ph. Zysset

I t d ti MCF L ll & BSU Ti CT QCT HR QCT

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Osteoporosis

FACTS IN AUSTRIA

750’000 patients

1 out of 3 women

1 out of 7 men12’000 hip fx a year

Chronic pain and impair.

20% mortality after 70

12’000 Euros per hip fxKoeck et al., Wiener Klin Wochen,

2001.

Bone mass as a function of age

TU Wien Ph. Zysset

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Introduction MCF Lamella & BSU Tissue µCT pQCT HR QCT

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Bone Hierarchical Organisation

The Bench Top

The mineralized collagen fibril (MCF, 200nm)

The lamella (2-7µm)The bone structural unit (BSU, 60µm)

Bone tissue, cortical shell or trabeculae (100-3000µm)

Trabecular bone (TB, mm)

Organ (cm)

The Bedside

TU Wien Ph. Zysset

Introduction MCF Lamella & BSU Tissue µCT pQCT HR QCT

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Outline

1 Introduction

2 MCF, Lamella & BSU

3 Tissue

4 µCT

5 pQCT

6 HR-QCT

TU Wien Ph. Zysset

Introduction MCF Lamella & BSU Tissue µCT pQCT HR-QCT

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Mineralized Collagen Fibril

Type I collagenApatite platelets

Water

Non-collagenous proteins

Currey, Princeton Press, 2002.

TU Wien Ph. Zysset

Introduction MCF Lamella & BSU Tissue µCT pQCT HR-QCT

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR QCT

Mineralized Collagen Fibril Array

Reisinger et al., work in progress.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR QCT

Lamellar Organization

Giraud-Guille, Calcif Tissue Int, 1988.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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, µ pQ Q

Bone Structural Unit

Eriksen et al., Raven Press, 1994.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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µ p

Mineralization and Orientation

Mean degree of mineralization

Polarized light microscopy (Paul Kasili)

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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µ

Outline

1 Introduction

2 MCF, Lamella & BSU

3 Tissue

4 µCT

5 pQCT

6 HR-QCT

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

I d i P i i l

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

I d i P i i l

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

I d t ti P i i l

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

I d t ti P i i l

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

I d t ti P i i l

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Indentation Principle

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Indentation Principle

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Indentation Principle

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Indentation Principle

t

P

h

P

t

t

h

t

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Indentation of Isotropic Materials

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Indentation of Isotropic Materials

dP

dh

hmax

Pmax

0.5 1.0 1.5h

2

4

6

8

10P

Oliver and Pharr (1992)

R E  =

√π dP 

dh(hmax )

2 A(hmax )

=E s 

1− ν 2s +

E t 

1− ν 2t 

I E  =

E s 

1

−ν 2s 

Oliver & Pharr, J Mater Res, 1992.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Indentation in Anisotropic Materials

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Indentation in Anisotropic Materials

I E (S, a3) =

4π 2π

0

B−1(t(γ ), S) : [a3 ⊗ a3]

 (a1/a2) cos2 γ + (a2/a1) sin2 γ dγ 

Swadener & Pharr, Phil Mag, 2001.

M min max

m1

-10

0

10m2

-20

-10

0

10

20

m3

-10

0

10

m1

m1

m2

m3

m1

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Human Vertebral Shell

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Human Vertebral Shell

0

10

10

0

10

20

0

20

32.6

50.2

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Human Vertebral Endplate

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Human Vertebral Endplate

20

10

0

10

20

20

10

0

10

20

10

0

10

31.8

39.5

Mazza et al., unpublished.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Trabecular tissue

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Trabecular tissue

10

0

10

10

0

10

20

10

0

10

20

39.

43.5

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Outline

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Outline

1 Introduction

2 MCF, Lamella & BSU

3 Tissue

4 µCT

5 pQCT

6 HR-QCT

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Trabecular Bone Morphometry

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Trabecular Bone Morphometry

Volume fraction BV/TVArea density BS/TV

Trabecular thickness TbTh

Trabecular separation TbSp

Trabecular number TbNbConnectivity density Conn.Dens.

Structure Model Index SMI

Individual plates and rods

Odgaard & Gundersen, Bone, 1993.Hildebrand & Ruegsegger, Comput Method Biomech, 1997.Hildebrand et al., J Bone Miner Res, 1999.Stauber et al., J Bone Miner Res, 2006.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Fabric

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Fabric

M =

3i =1

mi Mi  =

3i =1

mi (mi ⊗mi )

Harrigan & Mann, J Mater Sci, 1984.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Fabric-based Elasticity

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y

C(ρ, M) =3

i =1

1

ǫ0ρk m2l i 

Mi ⊗Mi 

−3

i < j =1

ν 0ǫ0ρk ml 

i ml  j 

(Mi ⊗M j  + M j ⊗Mi )

+

3i < j =1

1

2µ0ρk ml i m

l  j 

(Mi ⊗M j  + M j ⊗Mi )

ǫ0, µ0 and ν 0 are elastic constants of an asymptotic cubic material withρ = 1,m1 = m2 = m3 = 1 and k , l  are exponents.

Zysset & Curnier, Mech Mater, 1995.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Fabric-based Elasticity

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y

S

S

SS

SS

S

SSS

S

SS

S S

S S

S

S

S

S

SS

S

RRR

R RRRR

RR

RR

R

RR

T

T

TT

TTT

T

T T

TTTT

TT

TT

T

T

TT

T

T

TTTT

TT

TT

T T

T

TTT

TT T

T

T

T

T

TT

F

FF

FF

F

F F

FFF F

FF

FF

F

F

F

FFFFF

FFadj. R2

0.942

10 20 50 100 200 500 1000 200010

20

50

100

200

500

1000

2000

Experimental stiffness MPa

    P   r   e    d    i   c    t   e    d   s    t    i    f    f   n

   e   s   s

                  M    P   a              

O Multiaxial

O Torsion

O Tension

O Compression

Rincon-Kohli and Zysset, Biomech Model Mechan, 2009.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

FE Models: Voxel versus Smooth Surface

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Voxel

Segmentation

Cubic elements (voxels)

Smooth Surface

Segmentation + surface

Tetrahedral elements

Pahr, unpublished.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Validation Experiment

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p

MicroCT at 20 µm

Mechanical testing

NanoindentationVoxel-based FEA

Sub-region FEA

Chevalier et al., J Biomech, 2007.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Mechanical Test & FE

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TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Results

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Nanoindentation (dry)

MeanSD21.11.0 GPa

0 1 2 3 4 5 6 70

5

10

15

20

25

30

Samples

    T    i   s   s   u   e    M   o    d   u    l   u   s                  G    P

   a              

FE versus Experiments (dry)

 R20.978

BVTV: 932

0 500 1000 1500 2000 2500 3000 35000

500

1000

1500

2000

2500

3000

3500

Experimental Modulus MPa

    F    E    M   o    d   u    l   u   s                  M

    P   a              

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Sensitivity Analysis

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TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Outline

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1 Introduction

2 MCF, Lamella & BSU

3 Tissue

4 µCT

5 pQCT

6 HR-QCT

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

pQCT Resolution

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TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Experimental Colles’ Fracture

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Varga et al., J Biomech, in press.

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Experimental Colles’ Fracture

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TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Experimental Colles’ Fracture

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TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

pQCT of a 9mm Slice

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TU Wien Ph. Zysset

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FE Model of a 9mm Slice

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Results

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adj.R20.689

0 50 100 150 200 250 3000

2000

4000

6000

8000

10000

vBMD mgcc

    U    l    t    i   m   a    t   e    f   o   r   c   e

                  N              

adj.R20.219

0.0 0.1 0.2 0.3 0.4 0.50

2000

4000

6000

8000

10000

CtTh mm

    U    l    t    i   m   a    t   e    f   o   r   c   e

                  N              

adj.R20.946

0 50 100 150 200 250 3000

2000

4000

6000

8000

10000

microFE stiffness kNmm

    U    l    t    i   m   a    t   e    f   o   r   c   e

                  N              

adj.R20.935

0 2000 4000 6000 8000 10 0000

2000

4000

6000

8000

10000

FE ultimate force N

    U    l    t    i   m   a    t   e    f   o   r   c   e

                  N              

Varga et al., unpublished

TU Wien Ph. Zysset

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

QCT Resolution

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Sub-study of the EUROFORS Clinical Trial

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Multicenter

44 post-menopausal women(68±6.7 y.o.)

Teriparatide 20µg/day

DXA L1-L4

HRQCT T12

0,6,12,24 months

Graeff et al., J Bone Mineral Res, online.

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Voxel-Based Finite Element Modeling

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Model parameters:

Cubic elements of 1.3mm

Top and bottom PMMA layers

Density-based mat. properties

Homogeneous I-S architectureAxial loading

Output variables:

Stiffness:=load/displacementStrength:=maximum load

Distribution of damage Chevalier et al., ComputMethod Biomech, 2007.

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Introduction MCF, Lamella & BSU Tissueµ

CT pQCT HR-QCT

Results

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0.0 0.2 0.4 0.6 0.8 1.0

0

500

1000

1500

2000

2500

3000

3500

Displacement mm

    F   o   r   c

   e                  N              

Baseline

6 Mo

12 Mo

24 Mo

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Introduction MCF, Lamella & BSU Tissueµ

CT pQCT HR-QCT

Results

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Increase of strength in %

6 12 2450

0

50

100

MONTHS

    I    N    C    R    E    A    S    E

                                 

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Results

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0.0 0.2 0.4 0.6 0.8 1.00

500

1000

1500

2000

Displacement mm

    F   o   r   c   e                  N

              

Baseline

24 Months

24Mo

Base

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Results

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0.0 0.2 0.4 0.6 0.8 1.00

500

1000

1500

2000

Displacement mm

    F   o   r   c   e                  N

              

Baseline

24 Months

24Mo

Base

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Results

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0.0 0.2 0.4 0.6 0.8 1.00

500

1000

1500

2000

Displacement mm

    F   o   r   c   e                  N

              

Baseline

24 Months

24Mo

Base

TU Wien Ph. Zysset

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Results

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0.0 0.2 0.4 0.6 0.8 1.00

500

1000

1500

2000

Displacement mm

    F   o   r   c   e                  N

              

Baseline

24 Months

24Mo

Base

TU Wien Ph. Zysset

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Results

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0.0 0.2 0.4 0.6 0.8 1.00

500

1000

1500

2000

Displacement mm

    F   o   r   c   e                  N

              

Baseline

24 Months

24Mo

Base

TU Wien Ph. Zysset

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Results

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0.0 0.2 0.4 0.6 0.8 1.00

500

1000

1500

2000

Displacement mm

    F   o   r   c   e                  N

              

Baseline

24 Months

24Mo

Base

TU Wien Ph. Zysset

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Results

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0.0 0.2 0.4 0.6 0.8 1.00

500

1000

1500

2000

Displacement mm

    F   o   r   c   e              

    N

              

Baseline

24 Months

24Mo

Base

TU Wien Ph. Zysset

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Results

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0.0 0.2 0.4 0.6 0.8 1.00

500

1000

1500

2000

Displacement mm

    F   o   r   c   e              

    N

              

Baseline

24 Months

24Mo

Base

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Results

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0.0 0.2 0.4 0.6 0.8 1.00

500

1000

1500

2000

Displacement mm

    F   o   r   c   e                  N              

Baseline

24 Months

24Mo

Base

TU Wien Ph. Zysset

Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Acknowledgments

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Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Acknowledgments

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AO Foundation, Switzerland - AO Research Institute, Switzerland - CAE, Austria -

Celtis, Austria - Eli Lilly & Company, Europe - ESRF, France - ETH Lausanne,Switzerland - ETHZurich, Switzerland - FWF, Austria - Inselspital Bern, Switzerland -

Institut fur Unfallchirurgische Forschung und Biomechanik, Germany - Kuros

Biosurgery, Switzerland - Laboratoire d’Imagerie Parametrique, France - Ludwig

Boltzmann Institut fur Experimentelle und Klinische Traumatologie, Austria - Ludwig

Boltzmann Institut fur Osteologie, Austria - Ludwig-Maximilians Universitat Munchen,

Germany - Max-Planck-Institut fur Kolloid und Grenzflachen Forschung, Germany -

Med Uni Wien, Austria - Paracelsus Medizinische Universitat, Austria - Politecnico di

Milano, Italy - Sanofi-Aventis, USA - Technical University Prague, Czech Republic -

Technische Universitat Hamburg-Harburg, Germany - Universitat Bern, Switzerland -

Universitatsklinik Schleswig-Holstein, Germany - Universitatsmedizin Berlin, Germany

- University of Leeds, Great Britain, Veterinarmedizinische Universitat Wien, Austria -

VINforce, Austria

TU Wien Ph. Zysset