Bone has a specific density and structure
Bone remodeling
Experiments
Bert van Rietbergen
Wollf’s Law: mass and orientation of trabecular
structure are adapted to its mechanical load
But density and structure can change as a
result of changes in loading
• Disuse will lead to loss of bone
Graphical Statics
• wheelchair
• micro-gravity
• bedridden
• Overuse leads to formation of bone
• exercise
• tennis player
Wolff,1892
von Meyer &
Culmann,1866/67
Mechanism: osteoclast/osteoblast
Mechanism: osteoclast/osteoblast
Trabecular bone
Remodeling
1
Mechanism: osteocytes
Osteocytes as mechanosensor
OCy
• Generally accepted that ostecytes are
mechanosensors and regulate the remodeling
process because they:
•
•
•
•
lining cell
are sensitive to mechanical load
are sensitive to fluid flow
are the most abundant cell type in bone
can regulate OCl and OBl activity
Cyclic loading: fluid flow
Transport of nutrients and
waste products
Unloading: no fluid flow
Apoptosis of OCy
Attracts OCl
Osteocytes as mechanosensor
OCy
But...
• How is this process regulated?
lining cell
• How can this process leads to mechanically
‘optimized’ structures?
Microcracks: no fluid flow
Apoptosis of OCy
Attracts OCl
Experimental bone adaptation strategies
• 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?
Turkey ulna loading
• Overloading strategies @ normal strain-rates
• Turkey ulna loading
• Rat ulna loading
• Rat tail loading
• Rat exercise
• Sheep ulnar osteotomy
• Hypergravity
• Unloading strategies
• Rat tail suspension
• External fixation
• Rat hindlimb neurectomy/botox treatment
• Rat microgravity
• Human bed-rest
• High-frequency strategies
•
Rat ulna
• Sheep vibration platforms
• Human
2
Turkey ulna loading
Turkey ulna loading
Torsion versus axial
Change in total area
normal
Loaded
dynamically
Mean pore size
unloaded
Loaded
statically
Rubin et al., JBJSA, 1998
Rat ulna loading
Fatigue test
Rat ulna/tibia loading
Fatigue loading:
• 13 N @ 2Hz
• -2400/+1700 strain
• stop when reaching 60% increase in displacement
Turner et al., Bone, 1999
Rat ulna loading
Fatigue test
Sheep ulnar osteotomy
3-point bending
extrinsic
intrinsic
Lanyon et al., J.Biomech., 1982
3
Sheep ulnar osteotomy
Rat tail loading
BV/TV vs. loading
Change in bone structure vs. time @ 8N
Lambers et al., 2011
Rat exercise
backpack
Rat exercise
backpack
Histology
microCT
• Backpack: 20% BW
• Running 15 min/day
•19 weeks
Tromp et al., Calc.Tiss., 2006
Tail suspension
• Overloading strategies @ normal strain-rates
• Turkey ulna loading
• Rat ulna loading
• Rat tail loading
• Rat exercise
• Sheep ulnar osteotomy
• Hypergravity
• Unloading strategies
• Tail suspension
• external fixation
• Hindlimb neurectomy/botox treatment
• microgravity
• bed-rest
• High-frequency strategies
•
Rat ulna
• Sheep vibration platforms
• Human
4
Tail suspension
Tail suspension:
control
skull
humerus
23 days
femur
tibia
David et al., 2003; Barou et al., 2002
Tail suspension
Vico et al., 1995
Rat neurectomy
unilateral sciatic neurectomy
Aguirre et al., JBMR, 2006
Rat neurectomy
Brouwers et al., 2009
Microgravity
Long-term spaceflight: bone loss
Model:
• Bedrest studies
• Head 6o tilt down
• ~ several weeks
Brouwers et al., 2009
5
Human Bed-rest
Bedrest study
• 60 days bedrest
• Head 6o tilt down
Radius
Spaceflight
Tibia
Bedrest
Ambrecht et al., 2009
Countermeasures
Tibia
• Exercise group: every 3rd day
Change in strength over time
• Resistance training on ergometer
• Aerobics training: running on a
vertical treadmill
4%
4%
2%
2%
2%
0%
0%
0%
-2%
-2%
2%
-2%
2%
-4%
-4%
-4%
-6%
-6%
-6%
420
240
150
60
420
0
240
150
Radius
0
day
Bedrest period
• Additional amounts of protein and
free-leucine
60
420
240
150
0
60
day
• Nutrition group:
BR+Nu
BR+Ex
BR
4%
day
Individual subjects
Group average
Anova: change in strength since baseline
Tibia
Change in strength over time
Radius
BR+Ex
BR
BR+Nu
8%
8%
4%
8%
4%
4%
0%
0%
0%
-4%
-4%
-4%
-8%
-8%
-8%
day
420
240
150
60
Individual subjects
Group average
420
day
0
240
60
150
0
Bedrest period
420
240
60
150
0
day
*
* *
* Significantly different from baseline (p<0.05)
No significant differences between groups
6
Bone loss/gain analysis: tibia other subjects
Unloading due to placement of implants
BR period
BR
BR+Ex
BR+Nu
Unloading due to placement of implants
Cemented
Unloading due to placement of implants
Non-cemented
Unloading due to placement of implants
Unloading due to placement of implants
effect of implant
stiffness
'stress shielding'
Bobyn et al., 1990
7
Turkey ulna high frequency loading
• Overloading strategies @ normal strain-rates
• Turkey ulna loading
• Rat ulna loading
• Rat tail loading
• Rat exercise
• Sheep ulnar osteotomy
• Hypergravity
30 Hz
Neutral
axis
• Unloading strategies
• Tail suspension
• external fixation
• Hindlimb neurectomy/botox treatment
• microgravity
• bed-rest
• High-frequency strategies
•
Rat ulna
• Sheep vibration platforms
• Human
Turkey ulna high frequency loading
Qin et al., JOR, 1998
Turkey ulna high frequency loading
Strain threshold required to maintain bone mass
Control
Unloaded
100 strain
@30Hz
Rubin et al., 2001
Turkey whole-body vibration
Sheep whole-body vibration
• 12 months / 5days / week
• 20 min/day
• 30Hz
• 0.3g
femur
Rubin et al., 2001
Rubin et al., 2002
8
Sheep whole-body vibration
Rat whole-body vibration
vibration treatment
control
control
loaded
loaded
• 20 min/day, 5 days/week
• 6 weeks
• 0.3g, 90 Hz
Brouwers et al., 2009
Rat whole-body vibration
Rat whole-body vibration
Brouwers et al., 2009
Brouwers et al., 2009
Human whole-body vibration
Human whole-body vibration
control
vibration
• 48 young women (15-20y)
• 12 months
• 0.3g @ 30Hz
Gilsanz et al., 2006
Gilsanz et al., 2006
9
But...
• Overloading strategies @ normal strain-rates
• Turkey ulna loading
• Rat ulna loading
• Rat tail loading
• Rat exercise
• Sheep ulnar osteotomy
• Hypergravity
• Unloading strategies
• Tail suspension
• external fixation
• Hindlimb neurectomy/botox treatment
• microgravity
• bed-rest
• How is this process regulated?
• 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?
• High-frequency strategies
•
Rat ulna
• Sheep vibration platforms
• Human
10