Fragility Fractures - Pathogenesis-Biomechanical View
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Transcript of Fragility Fractures - Pathogenesis-Biomechanical View
11
Pathogenesis of Fragility Fractures:
A Biomechanical View
A.Arputha Selvaraj-APMP – IIM C
2
Outline
• Pathogenesis of fractures and determinants of bone
strength
• Age-related changes that contribute to skeletal fragility
• Interaction between skeletal loading and bone strength
• Non-invasive assessment of bone strength
3
Design of a structure
• Consider what loads it must sustain
• Design options to achieve desired function
– Overall geometry
– Building materials
– Architectural details
4
Determinants of whole bone strength
• Geometry
– Gross morphology (size & shape)
– Microarchitecture
• Properties of Bone Material / Bone Matrix
– Mineralization
– Collagen characteristics
– Microdamage
5
Hierarchical nature of bone structure
Seeman & Delmas N Engl J Med 2006; 354:2250-61
Macrostructure
Microstructure
Matrix Properties
Cellular Composition and Activity
6
FRACTURE?
Loads applied to the bone
Bone strength
Hayes et al. Radiol Clin N Amer. 1991; 29:85-96
Bouxsein et al. J Bone Miner Res. 2006; 21:1475-82
Applied load
Bone strength> 1 fracture
Factor ofrisk
Bone MassGeometry
Material properties
Fall traitsProtective responses
Bending, lifting
Biomechanical approach to fractures
7
Pathogenesis of fragility fractures
Age-related changes that contribute to fragility fractures:
1) Decreased bone strength
2) Increased propensity to fall
8
Assessing bone biomechanical properties
Deformation
Force
StructuralProperties
MaterialProperties
Biomechanical testing
Key properties
Displacement
Force
Failure load
Energy absorbed
Stiffness
10Review of the relevant material & geometric properties vs loading mode
compression
bending
Cross-sect area, A r2
Axial rigidity, E•A
Moment of inertia, I r4
Section modulus, Z r3
Bending rigidity, E•I
Material: Elastic modulus E (density)a Ultimate strength S (density)b
11
Effect of cross-sectional geometry on long bone strength
aBMD (by DXA) = =
Compressive strength
Bending strength
=
=
Bouxsein, Osteoporos Int, 2001
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Bone strength
SIZE & SHAPE macroarchitecturemicroarchitecture
MATERIAL tissue compositionmatrix properties
BONE REMODELINGformation / resorption
OSTEOPOROSIS DRUGS
Bouxsein. Best Practice Res Clin Rheumatol, 2005; 19:897-911
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Outline
• Determinants of bone strength
• Age-related changes that contribute to skeletal fragility
14
Age-related changes in mechanical properties of bone tissue
Cortical bone % loss 30-80 yrs
-8%
-11%
-34%
Elastic modulus, E
Ultimate strength, S
Toughness
Cancellous bone % loss 30-80 yrs
-64%
-68%
-70%
Bouxsein & Jepsen, Atlas of Osteoporosis, 2003
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Whole bone strength declines dramatically with age
0
2000
4000
6000
8000
10000 Femoral neck(sideways fall)
young
old
Courtney et al. J Bone Joint Surg Am. 1995; 77:387-95 Mosekilde. Technology and Health Care 1998; 6:287-97
Lumbar vertebrae(compression)
Wh
ole
bo
ne
str
en
gth
(N
ewto
ns
)
0
2000
4000
6000
8000
10000
youngold
16
Age-related changes in geometry Adaptation to maintain whole bone strength
17
Age-related changes in femoral neck vBMD, geometry, and strength indices
Trabecular vBMDCortical vBMD
Total areaMOIap
Axial rigidityBending rigidity
WomenF vs M
(P-value)Men% Change, ages 20-90 yrs
For age regressions: *P<0.05, **P<0.005
- 56** - 24**
13** - 1 - 39** - 25**
- 45** - 13**
7* - 21** - 31**- 24**
<0.001<0.001
ns ns ns ns
Riggs et al. J Bone Miner Res. 2004; 19:1945-54Riggs et al. J Bone Miner Res. 2006; 21(2):315-23
368 women, 320 men, aged 20-97
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Age-related changes in trabecular microarchitecture
• Decreased bone volume, trabecular thickness and number
• Decreased connectivity
• Decreased mechanical strength
Image courtesy of David Dempster
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Microarchitectural changes that influence bone strength
Force required to cause a slender column to buckle:
• Directly proportional to
– Column material
– Cross-sectional geometry
• Inversely proportional to– (Length of column)2 www.du.edu/~jcalvert/tech/machines/buckling.htm
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Theoretical effect of cross-struts on buckling strength
# Horizontal Effective Buckling Trabeculae Length Strength
0 L S
1 1/2 L 4 x S
Bouxsein. Best Practice Res Clin Rheumatol, 2005; 19:897-911
21
Cortical porosity increases with age(41 iliac biopsies, age 19-90)
Age (years)
0
3
6
9
12
15
0 20 40 60 80
r = 0.78 P < 0.001
(%)
Brockstedt et al. Bone 1993; 14:681-91
4-fold increase incortical porosity from
age 20 to 80
Increased heterogeneity with age
22
20-year-old 80-year-old
Age-related changes in femoral neck cortex and association with hip fracture
Those with hip fractures have:
• Preferential thinning of the inferior anterior cortex• Increased cortical porosity
Bell et al. Osteoporos Int 1999; 10:248-57 Jordan et al. Bone, 2000; 6:305-13
Mayhew et al, Lancet 2005
23
Age-related changes in bone properties associated with fracture risk
• Decreased bone mass and BMD
• Altered geometry
• Altered architecture
– Cortical thinning
– Cortical porosity
– Trabecular deterioration
Images from L. Mosekilde, Technology and Health Care. 1998
young
elderly
24
Outline
• Determinants of bone strength
• Age-related changes that contribute to femoral fragility
• Interaction between skeletal loading and bone strength
25
Etiology of age-related fractures
FRACTURE?
Loads applied to the bone
Bone strength
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Frx
no Frx
Applied load
Bone strength
The factor of risk concept
• Identify activities associated with fracture
• Use biomechanical models to determine loads applied to bone for
those activities
• Estimate bone failure load for those activities
=
Hayes et al. Radiol Clin N Amer. 1991; 29:85-96 Bouxsein et al. J Bone Miner Res. 2006; 21:1475-82
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Falls and hip fracture
• Over 90% of hip fx’s associated with a fall
• Less than 2% of falls result in hip fracture
• Fall is necessary but not sufficient condition
• Sideways falls are most dangerous
• What factors dominate fracture risk?
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Factor Adjusted Odds Ratio
Fall to side 5.7 (2.3 - 14)
Femoral BMD 2.7 (1.6 - 4.6)*
Fall energy 2.8 (1.5 - 5.2)**
Body mass index 2.2 (1.2 - 3.8)*
* calculated for a decrease of 1 SD** calculated for an increase of 1 SD
Greenspan et al, JAMA, 1994; 271(2):128-33
Independent risk factors for hip fracture
29
Estimating loads applied to the hip during a sideways fall
Human cadavers
Human volunteers
Crash dummy
Mathematical models and simulations
Peak impact forces applied to greater trochanter:
270 - 730 kg (2400 - 6400 N)(for 5th to 95th percentile woman)
Robinovitch et al. 1991; Biomech Eng. 1991; 113:366-74
Robinovitch et al.1997; Ann Biomed Eng. 1997; 25:499-508
van den Kroonenberg et al J Biomechanic Engl.1995; 117:309-18 van den Kroonenberg et al J Biomech. 1996; 29:807-11
30
Femur is strongest in habitual loading conditions
Keyak et al. J Biomech. 1998; 31:125-33
0123456789
Stance Sideways fall
Fa
ilure
loa
d (
kN
)
P < 0.001
2318 ± 300 N7978 ± 700 N
31
Femur is strongest in habitual loading conditions
Keyak et al. J Biomech. 1998; 31:125-33 van den Kroonenberg et al. J Biomech. 1996; 29:807-11
0123456789
Stance Sideways fall
Fa
ilure
loa
d (
kN
)
P < 0.001
2318 ± 300 N7978 ± 700 N
= Applied load
Failure load
Thus, > 1 for sideways fall in elderly persons
Fall load
32
Vertebral fractures
• Difficult to study– Definition is controversial
– Many do not come to clinical attention
– Slow vs. acute onset
– The event that causes the fracture is often unknown
• Poor understanding of the relationship between spinal loading and vertebral fragility
33
Estimating loads on the lumbar spine
Schultz et al.1991; Spine. 1991; 16:1211-6 Wilson et al.1994; Radiology. 1994 ; 193:419-22 Bouxsein et al. J Bone Miner Res. 2006; 21:1475-82
34
Factor of risk for vertebral fracture (L2)Bending forwards 90o with 10 kg weight in hands
Age
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
10 20 30 40 50 60 70 80 90 100
Men
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
10 20 30 40 50 60 70 80 90 100Age
Women
11.9% 30.1%
+92% over life** †+28% over life**
** P<0.005 for age-regressions
† p<0.01 for comparison of age-related change in M and W
Bouxsein et al. J Bone Miner Res. 2006; 21:1475-82
35
Proportion of individuals with
> 1, per decade
0
10
20
30
40
50
60
20-29 30-39 40-49 50-59 60-69 70-79 80+
%
4%4% 11% 12%
21%11%
27%
42%
53%
Age
(Bending forwards 90o lifting 10 kg weight)
0
200
400
600
800
1000
1200
1400
40 50 60 70 8030 90
Incidence / 100,000 person-years
Bouxsein et al. J Bone Miner Res. 2006; 21:1475-82
36
Outline
• Determinants of bone strength
• Age-related changes that contribute to femoral fragility
• Interaction between skeletal loading and bone strength
• Non-invasive assessment of bone strength
37
Bouxsein et al, 1999
• Does not distinguish– Specific attributes of 3D geometry– Cortical vs cancellous density– Trabecular architecture– Intrinsic properties of bone matrix
Clinical assessment of bone strength by DXA
• Areal BMD by DXA– Bone mineral / projected area (g/cm2)
• Reflects (indirectly)– Geometry / Mass / Size– Mineralization
• Moderate to strong correlation with whole bone strength at spine, radius & femur (r2 = 50 - 90%)
• Strong predictor of fracture risk
38
Estimating hip geometry from 2D DXA “Hip Strength Analysis”
Estimate femoral geometry and strength indices • Use 2D image data to derive 3D geometry• Requires assumptions that have not been tested for all populations and
treatments
Beck et al. 1999, 2001
39
QCT assessment of bone density and geometry
Images courtesy of Dr. Thomas Lang, UCSF
40
Non-Fx
62 yr
Fx
62 yr
Ito et al. J Bone Miner Res. 2005; 20:1828-36
Multi-detector computed tomography
Potential to show trabecular architecture…
Higher resolution, but higher radiation dose
41
Trabecular architecture in vivowith high resolution pQCT
~ 80 µm3 voxel size
~ 3 min scan time, < 4 µSv
Distal radius and tibia only
Reproducibility: density: 0.7 - 1.5% * µ-architecture: 1.5 - 4.4% *
Xtreme CT, Scanco
* Boutroy et al. J Clin Endocrinol Metab. 2005; 90:6508-15
42
Premenopausal
Postmenopausal Osteopaenia
Postmenopausal Osteoporosis
PostmenopausalSevere Osteoporosis
Boutroy et al. J Clin Endocrinol Metab. 2005; 90:6508-15
Tibia Radius
43
Discrimination of osteopaenic women with and without history of fracture by HR-pQCT
(age = 69 yrs, n=35 with prev frx, n=78 without fracture)
* p < 0.05 vs fracture free controls
Boutroy et al. J Clin Endocrinol Metab. 2005; 90:6508-15
0.4%
-12%*-9%*
13%*
26%*
-0.3%
-10%
0%
10%
20%
30%
SpineBMD
Fem NeckBMD BV/TV TbN
TbSp TbSpSD
% D
iffer
en
ce
TbTh
-5%
44
MRI for architecture assessment in vivo
• Features of MRI
– Non-invasive
– No x-rays
– True 3D
– Oblique scanning plane
– Clinical scanners
– Image time: 12 - 15 minutes
~ 150 x 150 x 300 µm,
60 x 60 x 100 µm
Image courtesy of Dr. Felix Wehrli, UPenn
Image courtesy of Dr. Sharmila Majumdar, UCSF
45
Images from two women with similar BMD
www.micromri.com
MRI assessment of trabecular structure
46
Crawford et al, Bone 2003; 33: 744-750
QCT-based finite element analysis
• FEA is a well-established engineering method for analysis of complex structures
• Integrates geometry and density information from QCT scan to provide measures of bone strength
• In some cases, more strongly associated with whole bone strength in cadavers than DXA
• Further clinical validation needed
Image courtesy of T. Keaveny
Faulkner et al, Radiology 1991; Keyak et al, J Biomechanics 1998; Pistoia, Bone 2002; van Rietbergen JBMR 2003; Crawford et al, Bone 2003
47
Conclusions
• Whole bone strength is determined by bone mass, geometry, microarchitecture and characteristics of bone material
• Hip fractures result from an increase in traumatic loading — in particular, falls to the side — coupled with a deterioration in bone strength with increased age
• Biomechanically based assessment of fracture risk may improve diagnosis and understanding of treatment effects
• New tools are being developed for non-invasive assessment of bone strength and fracture risk