Bone%20Quality%20PART%202%20Damage%20Accumulation%20Degree%20of%20Mineralization%20Biomechanics

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Bone QualityPART 2Damage AccumulationDegree
of MineralizationBiomechanics
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Bone Quality
Architecture Turnover Rate Damage
Accumulation Degree of Mineralization Properties
of the Collagen/Mineral Matrix
Adapted from NIH Consensus Development Panel on
Osteoporosis. JAMA 285785-95, 2001
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Dogs Treated with High Doses of Bisphosphonates
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Microcrack Surface Density(?m/mm2) Mean SEM
10
5
0
Placebo
Risedronate
Alendronate
Reproduced with permission from Mashiba T et al.
J Bone Miner Res 15613-620 2000
Plt.05 vs placebo Plt.01 vs placebo
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Microcracks
Risedronate
Alendronate
Microcracks in the third lumbar vertebral body
from an alendronate treated dog
Microcrack in the right femoral neck cortex from
a risedronate treated dog
Reproduced with permission from Mashiba T et al.
Bone 28524-531, 2001
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Effect of Long-Term Bisphosphonate Treatment -
Incadronate
Reproduced with permission from Komatsubara S. J
Bone Miner Res 18 512-520, 2003
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(No Transcript)
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Microdamage in Human Trabecular and Cortical Bone
Reproduced with permission from Seeman E.
Advances in Osteoporotic Fracture Management 2
2-8, 2002 and Fyhrie DP. Bone 15105-109, 1994
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Bone Quality
Architecture Turnover Rate Damage
Accumulation Degree of Mineralization Properties
of the Collagen/Mineral Matrix
Adapted from NIH Consensus Development Panel on
Osteoporosis. JAMA 285785-95, 2001
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Bone Mineralization of the Basic Multicellular
Unit
100 - 50 - 0 -
Degree of Mineralization ()
Time
Secondary mineralization (years)
Primary mineralization (3 months)
Ott S. Advances in Osteoporotic Fracture
Management 2 48-54, 2003
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Homogeneous vs. Heterogeneous Mineralization

• Microdamage progression is prevented by the
  roughness (or heterogeneity) of mineral densities
  and differing directions of mineralized collagen
  present.
• Cracks require energy to progress through bone,
  and when the mineral density is high and
  distribution of the tissue mineral density is
  homogeneous less energy (derived from
  deformation) is required for microdamage
  progression.

Seeman E. Advances in Osteoporotic Fracture
Management 2 2-8, 2002
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Homogeneous vs. Heterogeneous Mineralization
Heterogeneous
Homogeneous
Low mineralization
High mineralization
Adapted with permission from Boivin et al. Bone
27687-694 2000
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Heterogeneous Mineral Distribution in Iliac Bone
Reproduced with permission from Boivin GJ.
Musculoskel Neuron Interact 2 538-543, 2002.
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The Relationship Between Mineralization and Bone
Strength is Complex
Reproduced with permission from Seeman E.
Advances in Osteoporotic Fracture Management 2
2-8 2002 and Currey JD. J Biomechanics 12
459-469 1979
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Effects of Alendronate on Bone Mineralization in
Ovariectomized Monkeys
ALN
OVX
CTRL
Number of Measurements
.2 .4 .6 .8 1.0 1.2 1.4 1.6 1.8
Degree of Mineralization (g mineral/cm3)
Meunier and Boivin. Bone 21373-7, 1997
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Alendronate Increases Bone Mineralization in
Women with Osteoporosis
Two Years
Three Years
.50 .60 .70 .80 .90 1.0 1.2 1.3 1.4 1.5 1.6
Adapted with permission from Boivin et al. Bone
27687-694 2000
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Raloxifene Treatment Induces a Normal Pattern of
Bone Mineralization
Two-year treatment with raloxifene results in a
moderate increase in mineralization and
preservation of heterogeneous mineral
distribution
Boivin G. ECTS Meeting, P190, 2003.
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Biomechanics
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What Contributes to Bone Strength?

• Quantity of bone
• Structural Properties
• Size and shape of bone
• Trabecular connectivity
• Trabecular shape
• Overall Quality
• Microdamage, etc.
• Material Properties
• Collagen/mineral matrix

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Biomechanical Evaluation of Whole Bone
Compression test of femoral neck
Three-point bending of femoral midshaft
Compression test of lumbar vertebral body
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Whole Bone Properties

• Strength
• Stiffness
• Brittleness
• Energy (work to failure)

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A Pharmacological Agent Should Increase Bone
Strength While Also Decreasing Brittleness



Point of Failure
Turner CH et al. Osteoporos Int 1397-104 2002
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Mineralization Affects Brittleness
Turner CH et al. Osteoporos Int 1397-104 2002
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(No Transcript)
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Cross-Sectional Moment of Inertia
CSMI ? A ? d2
y
A
dz
x
dx
z
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Cross-Sectional Moment of Inertia CSMI ?/4
(r4 outer r4 inner)
Area (cm2) 2.77 2.77 2.77 CSMI (cm4) 0.61 1.06 1.5
4 Bending Strength 100 149 193
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Cross-Sectional Moment of Inertia
Adapted from Lee CA, and Einhorn TA. Osteoporosis
2nd Ed. 2001
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Relative Influence of Inner and Outer Diameters
on Bone Strength
Adapted from Lee CA, and Einhorn TA. Osteoporosis
2nd Ed. 2001
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Local Buckling
thickness
radius
Local buckling in hollow tubes becomes likely
when the buckling ratio is gt 10
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Local Buckling
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Reprinted with Permission Beck TJ J Bone Miner
Res 15 2297-2304, 2000 Beck TJ J Bone Miner Res
16 1108-1119, 2001
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Material Properties of Bone

• Material strength
• Elastic modulus (Youngs modulus)
• Toughness

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Biomechanics General
Adapted from, Lee and Einhorn, 2001
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Biomechanics Examples
Taffy
Glass
Bone
Elastic Deformation
Failure
Failure
Plastic Deformation
Force/area (Stress)
Force/area (Stress)
Failure
Force/area (Stress)
Deformation (Strain)
Deformation (Strain)
Deformation (Strain)
Adapted from, Lee and Einhorn, 2001
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Relationship of Mineralization to Toughness
Youngs Modulus (Stiffness)
Toughness
Hypermineralization
Hypomineralization
Mineral Content
Adapted from Wainwright, Biggs, Currey and
Gosline. Mechanical Design in Organisms.
Princeton Press, 1976
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Structural Determinants of Bending Strength
E Youngs modulus of Elasticity (material
property)
I Cross Sectional Moment of Inertia
(geometrical property)
Adapted from, Lee CA, and Einhorn TA.
Osteoporosis 2nd Ed. 2001
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Toughness versus Stiffness
Reproduced with permission from Seeman E Advances
in Osteoporotic Fracture Management 22-8 2002
and Currey JD J Biomechanics 12 459-469 1979
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Bone is Tough and Stiff
Osteomalacia
Osteopetrosis