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Bone density and shape adapt to loading
Turkey Ulna experiments
(Rubin et al)
Sheep ulnar osteotomy
(McNamara)
Bone remodeling simulation models
Bert van Rietbergen
• Bone is deposited in regions of high loading
• Load-dependent response
• Only dynamic loading results in bone apposition
Bone remodeling
But...
• Generally accepted that ostecytes are
mechanosensors and regulate the remodeling
process because they:
• How is this process regulated?
•
•
•
•
are sensitive to mechanical load
are sensitive to fluid flow
are the most abundant cell type in bone
can regulate OCl and OBl activity
Frost: mechanostat theory
• How can this process leads to mechanically
‘optimized’ structures?
• H
How can cells
ll att the
th scale
l off 10 microns
i
produce
d
'optimal' structures at a scale 100-1000 times larger?
Bone remodeling theory
Cowin et al., “Theory of Adaptive Elasticity” (1974)
Carter et al., Huiskes et al., Beaupre et al., .....
o e adapts its
ts mass
ass to mechanical
ec a ca demands
de a ds
Bone
Bone mass
Sref mechanical signal: S
Frost, 1960
'lazy zone'
1
Mechanical signal S ?
Mechanostat theory
something that can be measured by osteocytes
• Stress/strain parameters
• peak/average strain 
• strain-rate 
• Can it explain bone shape adaptation?
• strain energy density U or U/
• ‘energy stress’ 2 EU
• von Mises stress 
• Physiological loading
•
•
•
•
accumulated microdamage
fluid flow
cell wall shear stress
.....
Analysis of stress/strain distribution:
FE-method
Simulation of bone remodeling process
bone geometry
t=t+t
Update Geometry
FE-model
Change in bone mass
dM
 A  S  Sref
dt
?

mechanical signal: S
Brown et al., 1990
Simulation of bone remodeling process:
Turkey ulna
Martinez and Cerrolaza, 2005
Beaupre et al., 1990, Huiskes et al., 1991
Simulation of bone remodeling process:
Bone straightening
Roberts and Hart, 2005
2
Mechanostat theory
Simulation of bone remodeling process

Stiffness distribution
• Can it explain bone shape adaptation?
• Can it explain bone density distribution?
t=t+t
Update Stiffness
E=c
Change in bone mass
d
 A  S  S ref
dt

mechanical signal: S
Beaupre et al., 1990, Huiskes et al., 1991
Wolff's law can explain density distribution
Bone remodeling simulation models
• as a pre-clinical tool to evaluate implants
initial density
final
Weinans et al., 1995
Application: prediction of adverse bone
resorption
Bone loss around implants:
result of "Stress shielding"
3
Simulation of bone remodeling process
Bone remodeling simulation: cemented stems
Stiffness distribution
t=t+t
Change in bone Stiffness
E=c
Change in bone mass
d
 A  S  S ref
dt

mechanical signal: S
Beaupre et al., 1990, Huiskes et al., 1991
Weinans et al, 1992
Bone remodeling simulation: uncemented
stems
Weinans et al, 1992
Effect of stem fixation and material on normal
stress
Weinans et al, 1992
3D Simulation of bone remodeling process
site specific remodeling required
Stiffness distribution
Site-specific vs. non-site specific
• Non-site specific Sref= constant
• Site specific:
t=t+t
• Sref= dependent on the location
• Usually large 'lazy zone' required
Change in bone Stiffness
E=c
Change in bone mass
d
 A  S  S ref
dt

Bone mass
Sref mechanical signal: S
mechanical signal: S
reference signal: Sref
'lazy zone'
4
Bone remodeling / interface stress analysis
as a pre-clinical tool
Bone remodeling simulation: 3D
g/cm-3
MPa
-2.0
0
gcm-3
0.0
0.0
2.0
1.8
1.8
pre-remodeling
post-remodeling
Remodeling simulation validation
Comparison with DEXA
pre-remodeling
post-remodeling
Normal stresses
pre-remodeling
post-remodeling
Shear stresses
Mechanostat theory

• Can it explain bone shape adaptation?
• Can it also explain bone density distribution?
• Can it explain bone morphology?

Kerner et al. 1999
Predicted density not smooth
Weinans et al., J.Biomech, 1992
"Plate model"
Weinans et al., J.Biomech, 1992
5
"Plate model"
Problem
• Results will be mesh dependent
• Solution: decouple biology from FE-mesh
.
.
.
.
.
.
.
.
.
.
.
.
Weinans et al., J.Biomech, 1992
Spatial decay osteocyte stimulus
Simulation of bone morphogenesis
1
f
f (d )  e

2
d
D
2 mm
d
80x80 elements
Mullender and Huiskes, JOR, 1995
Simulation of bone morphogenesis
Mullender and Huiskes, JOR, 1995
Simulation morphogenesis
2 Mpa external stress,
cycling at 1.0 Hz
(1.5 mm)
Mullender and Huiskes, JOR, 1995
3
Ruimerman et al, J of Biomechanics, 2005
6
Simulation of adaptation


Tanck et al, Bone 28, 2001
Computer Simulation
Ruimerman et al, J of Biomechanics, 2005
Ruimerman et al, J of Biomechanics, 2005
Mechanostat theory
•
•
•
•

Can it explain bone shape adaptation?
Can it also explain bone density distribution?
Can it explain bone morphology?
Can it explain remodeling at the tissue level

• osteoblasts and osteoclasts always go together

Hypothesis: Strain as the coupling factor in
remodeling
Quiescence
Resorption
cavity
Mechanically regulated
formation
Development trabecular BMU
Quiescence
stress
LC
Ocy
Oc
e-Ob
Ob
elevated
strain
Huiskes et al., Nature, 2000
n-Ocy
recruitment
stimulus
3x3 mm2
7
Development trabecular BMU
Development trabecular BMU
Eriksen, Endocr. Rev. 1986
Can the theory also explain remodeling in
cortical bone?
Development cortical BMU
Haversian system
Osteon
2x2 mm2
Development cortical BMU
30 degrees rotated load
no load
2x2 mm2
8
A unified theory for osteonal and hemiosteonal remodeling
Clinical application
• Major problem: physiological loading conditions are
not know
?
van Oers et al., Bone, 2008
Other hypotheses
Mechanostat theory
•
•
•
•
This afternoon

Can it explain bone shape adaptation?
Can it also explain bone density distribution?
Can it explain bone morphology?
Can it explain remodeling at the tissue level

• Use a matlab code to simulate bone remodeling


9