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

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

TU Wien Ph. Zysset

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

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

What is Biomechanics?

”Biomechanics is the science of ...

motion,
forces,
equilibrium
...and
the behavior of living matter.”

TU Wien Ph. Zysset

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

The Bone Syndrome

TU Wien Ph. Zysset

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

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 men
12’000 hip fx a year
Chronic pain and impair.
20% mortality after 70
12’000 Euros per hip fx
Koeck et al., Wiener Klin Wochen, Hip fracture
2001.

TU Wien Ph. Zysset

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 men
12’000 hip fx a year
Chronic pain and impair.
20% mortality after 70
12’000 Euros per hip fx
Koeck et al., Wiener Klin Wochen, Bone mass as a function of age
2001.

TU Wien Ph. Zysset

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

Bone Mechanics

Residual stresses
Elasticity
Viscoelasticity Poroelasticity

Damage
Initiation Accumulation

Strength
Impact Toughness Fatigue

Growth Remodeling Aging Disease Treatment

TU Wien Ph. Zysset

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

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

Mineralized Collagen Fibril

Type I collagen
Apatite platelets
Water
Non-collagenous proteins

Currey, Princeton Press, 2002.

TU Wien Ph. Zysset

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

Lamellar Organization

Giraud-Guille, Calcif Tissue Int, 1988.

TU Wien Ph. Zysset

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

Bone Structural Unit

Eriksen et al., Raven Press, 1994.

TU Wien Ph. Zysset

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

Mineralization and Orientation

Polarized light microscopy (Paul Kasili)

Mean degree of mineralization

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation Principle

P P

t h
t t

t h

TU Wien Ph. Zysset

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

Indentation of Isotropic Materials

Oliver and Pharr (1992)

P
10 √ dP
R π (hmax )
Pmax E = pdh
8
2 A(hmax )
Es Et
6
= +
1 − νs2 1 − νt2
dP
4
dh I Es
E =
2
1 − νs2
hmax
0.5 1.0 1.5
h Oliver & Pharr, J Mater Res, 1992.

TU Wien Ph. Zysset

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

Indentation in Anisotropic Materials

I 4π
E (S, a3 ) = Z 2π
B (t(γ), S) : [a3 ⊗ a3 ]
−1
p dγ
0 (a1 /a2 ) cos2 γ + (a2 /a1) sin2 γ

Swadener & Pharr, Phil Mag, 2001.

M min max

20

10

m3
0
m3

-10

-20
-10
-10
m1
0
0
m1 m2
m2 10 10

TU Wien Ph. Zysset

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

Human Vertebral Shell

-10
10 0
10
0

-10

50.2
20

32.6

-20

TU Wien Ph. Zysset

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

Human Vertebral Endplate

20
10

-10

-20
39.5

10

-10
31.8

-20
-10
0
10

20

Mazza et al., unpublished.

TU Wien Ph. Zysset

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

Trabecular tissue

10

-10

20
43.5

10

-10
39.

-20

-10
0
10

TU Wien Ph. Zysset

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

Trabecular Bone Morphometry

Volume fraction BV/TV

Area density BS/TV
Trabecular thickness TbTh
Trabecular separation TbSp
Trabecular number TbNb
Connectivity density Conn.Dens.
Structure Model Index SMI
Individual plates and rods

Odgaard & Gundersen, Bone, 1993.

Hildebrand & Rüegsegger, 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

3
X 3
X
i
M= mi M = mi (mi ⊗ mi )
i =1 i =1

Harrigan & Mann, J Mater Sci, 1984.

TU Wien Ph. Zysset
Introduction MCF, Lamella & BSU Tissue µCT pQCT HR-QCT

Fabric-based Elasticity

3
X 1
C(ρ, M) = Mi ⊗ Mi
ǫ ρk mi2l
i =1 0
3
X ν0
− (Mi ⊗ Mj + Mj ⊗ Mi )
i <j=1 0
ǫ ρ mil mjl
k

3
X 1
+ (Mi ⊗Mj + Mj ⊗Mi )
i <j=1
2µ0 ρk mil mjl

ǫ0 , µ0 and ν0 are elastic constants of an asymptotic cubic material with

ρ = 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

2000
FF
F F
adj. R2 =0.942 FT FF
T FTFF F T
1000 FTTFFT
F
T F FT
RRFTTRT
T
T
RTTT TR
500 TTTRTTRTT

Predicted stiffness @MPaD

TRT T S
R
S
R R R
TTTR
STS ST
SSS F STF
F SS T
200 T SFSSSFT F
T
T S
S
T TSS S
ST O Compression
100 S
T T
T
RR O Tension
50
S
O Torsion

20
O Multiaxial

10
10 20 50 100 200 500 1000 2000
Experimental stiffness @MPaD

Rincón-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

Voxel Smooth Surface

Segmentation Segmentation + surface
Cubic elements (voxels) Tetrahedral elements
Pahr, unpublished.

TU Wien Ph. Zysset

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

Validation Experiment

MicroCT at 20 µm
Mechanical testing
Nanoindentation
Voxel-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

TU Wien Ph. Zysset

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

Results

FE versus Experiments (dry)

3500
Nanoindentation (dry)
3000 BVTV: 9-32%
30
2500

FE Modulus @MPaD
Tissue Modulus @GPaD

25
20 2000
15
10
1500
Mean±SD=21.1±1.0 @GPaD
5 1000
0
0 1 2 3 4 5 6 7
Samples 500 R2=0.978
0
0 500 1000 1500 2000 2500 3000 3500
Experimental Modulus @MPaD

TU Wien Ph. Zysset

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

Sensitivity Analysis

TU Wien Ph. Zysset

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

pQCT Resolution

TU Wien Ph. Zysset

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

Experimental Colles’ Fracture

Varga et al., J Biomech, in press.

TU Wien Ph. Zysset

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

Experimental Colles’ Fracture

TU Wien Ph. Zysset

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

Experimental Colles’ Fracture

TU Wien Ph. Zysset

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

pQCT of a 9mm Slice

TU Wien Ph. Zysset

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

FE Model of a 9mm Slice

TU Wien Ph. Zysset

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

Results
10 000 10 000
Ultimate force @ND

Ultimate force @ND

8000 8000
ææ
æ
æ æ ææ
æ
6000 6000
æ æ
æ æ
4000 ææ 4000 ææ
æ æ æ æ ææ
æ ææææ æ æ ææ æ æææ
2000 æ 2000
æ ææ adj.R 2 =0.689 æ ææ adj.R 2=0.219
0 0
0 50 100 150 200 250 300 0.0 0.1 0.2 0.3 0.4 0.5
vBMD @mgccD CtTh @mmD
10 000 10 000
Ultimate force @ND

Ultimate force @ND

8000 8000
æ æ æ æ
ææ ææ
6000 6000
æ æ
æ æ
4000 æ 4000 ææ æ
ææ
ææ æ
æ ææ æ
ææ æææ æ
2000 æ
ææ
æ adj.R 2 =0.946 2000 ææææ adj.R 2 =0.935

0 0
0 50 100 150 200 250 300 0 2000 4000 6000 8000 10 000
microFE stiffness @kNmmD FE ultimate force @ND

Varga et al., unpublished

TU Wien Ph. Zysset

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

QCT Resolution

TU Wien Ph. Zysset

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

Sub-study of the EUROFORS Clinical Trial

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.

TU Wien Ph. Zysset

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

Voxel-Based Finite Element Modeling

Model parameters:
Cubic elements of 1.3mm
Top and bottom PMMA layers
Density-based mat. properties
Homogeneous I-S architecture
Axial loading

Output variables:
Stiffness:=load/displacement
Strength:=maximum load
Distribution of damage Chevalier et al., Comput
Method Biomech, 2007.

TU Wien Ph. Zysset

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

Results

3500

3000
24 Mo
2500
Force @ND

12 Mo
2000

1500 6 Mo

1000
Baseline
500

0
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

Increase of strength in %

*
*
100 *
*
INCREASE @%D

50

*
-50
6 12 24
MONTHS

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Results

24Mo
2000
Force @ND

1500

1000
24 Months
500
Baseline

0 Base
0.0 0.2 0.4 0.6 0.8 1.0
Displacement @mmD

TU Wien Ph. Zysset

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

Acknowledgments

TU Wien Ph. Zysset

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

Acknowledgments
AO Foundation, Switzerland - AO Research Institute, Switzerland - CAE, Austria -
Celtis, Austria - Eli Lilly & Company, Europe - ESRF, France - ETH Lausanne,
Switzerland - ETHZürich, Switzerland - FWF, Austria - Inselspital Bern, Switzerland -
Institut für Unfallchirurgische Forschung und Biomechanik, Germany - Kuros
Biosurgery, Switzerland - Laboratoire d’Imagerie Paramétrique, France - Ludwig
Boltzmann Institut für Experimentelle und Klinische Traumatologie, Austria - Ludwig
Boltzmann Institut für Osteologie, Austria - Ludwig-Maximilians Universität München,
Germany - Max-Planck-Institut für Kolloid und Grenzflächen Forschung, Germany -
Med Uni Wien, Austria - Paracelsus Medizinische Universität, Austria - Politecnico di
Milano, Italy - Sanofi-Aventis, USA - Technical University Prague, Czech Republic -
Technische Universität Hamburg-Harburg, Germany - Universität Bern, Switzerland -
Universitätsklinik Schleswig-Holstein, Germany - Universitätsmedizin Berlin, Germany
- University of Leeds, Great Britain, Veterinärmedizinische Universität Wien, Austria -
VINforce, Austria

TU Wien Ph. Zysset