Fragility Fractures - Pathogenesis-Biomechanical View

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Fragility Fractures - Pathogenesis-Biomechanical View

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  • Engineering theory predicts that the strength of a column to resist buckling under a load (or force) is related to three things: column materials, the cross-sectional geometry of the column, and the length of the column. The theory that explains these relationships is the “Euler Buckling Theory”. The next slide provides more perspective, with an emphasis on the role of column length .
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  • Now for looking at trabecular bone, one must realize that MRI only sees mobile protons, as in soft tissue. So … Can be a confounding problem for in-vitro work, as air gaps or bubbles will give 0 signal, and thus be classified as bone.
  • Fragility Fractures - Pathogenesis-Biomechanical View

    1. 1. 1 Pathogenesis of Fragility Fractures: A Biomechanical View A.Arputha Selvaraj-APMP – IIM C
    2. 2. 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. 3. 3 Design of a structure • Consider what loads it must sustain • Design options to achieve desired function – Overall geometry – Building materials – Architectural details
    4. 4. 4 Determinants of whole bone strength • Geometry – Gross morphology (size & shape) – Microarchitecture • Properties of Bone Material / Bone Matrix – Mineralization – Collagen characteristics – Microdamage
    5. 5. 5 Hierarchical nature of bone structure Macrostructure Microstructure Matrix Properties Cellular Composition and Activity Seeman & Delmas N Engl J Med 2006; 354:2250-61
    6. 6. 6 Biomechanical approach to fractures Fall traits Protective responses Bending, lifting Loads applied to the bone FRACTURE? Bone Mass Geometry Material properties Factor of risk Bone strength Applied load Bone strength Hayes et al. Radiol Clin N Amer. 1991; 29:85-96 Bouxsein et al. J Bone Miner Res. 2006; 21:1475-82 >1 fracture
    7. 7. 7 Pathogenesis of fragility fractures Age-related changes that contribute to fragility fractures: 1) Decreased bone strength 2) Increased propensity to fall
    8. 8. 8 Assessing bone biomechanical properties Structural Properties Material Properties Force Deformation
    9. 9. Biomechanical testing Key properties Failure load Force Stiffness Energy absorbed Displacement
    10. 10. Review of the relevant material & geometric properties vs loading mode Material: Elastic modulus Ultimate strength compression bending E ∝ (density)a S ∝ (density)b Cross-sect area, A ∝ r2 Axial rigidity, E•A Moment of inertia, I ∝ r4 Section modulus, Z ∝ r3 Bending rigidity, E•I 10
    11. 11. 11 Effect of cross-sectional geometry on long bone strength aBMD (by DXA) = = ↓ Compressive strength = ↑ ↑ Bending strength = ↑↑ ↑↑↑ Bouxsein, Osteoporos Int, 2001
    12. 12. 12 Bone strength SIZE & SHAPE macroarchitecture microarchitecture MATERIAL tissue composition matrix properties BONE REMODELING formation / resorption OSTEOPOROSIS DRUGS Bouxsein. Best Practice Res Clin Rheumatol, 2005; 19:897-911
    13. 13. 13 Outline • Determinants of bone strength • Age-related changes that contribute to skeletal fragility
    14. 14. 14 Age-related changes in mechanical properties of bone tissue Cortical bone % loss 30-80 yrs Cancellous bone % loss 30-80 yrs Elastic modulus, E -8% -64% Ultimate strength, S -11% -68% Toughness -34% -70% Bouxsein & Jepsen, Atlas of Osteoporosis, 2003
    15. 15. 15 Whole bone strength (Newtons) Whole bone strength declines dramatically with age 10000 Femoral neck (sideways fall) 8000 6000 4000 10000 Lumbar vertebrae (compression) 8000 young 6000 old 2000 0 Courtney et al. J Bone Joint Surg Am. 1995; 77:387-95 Mosekilde. Technology and Health Care 1998; 6:287-97 4000 2000 0 young old
    16. 16. Age-related changes in geometry Adaptation to maintain whole bone strength 16
    17. 17. Age-related changes in femoral neck vBMD, geometry, and strength indices % Change, ages 20-90 yrs Men Women F vs M (P-value) Trabecular vBMD Cortical vBMD - 56** - 24** - 45** - 13** <0.001 <0.001 Total area MOIap Axial rigidity Bending rigidity 13** -1 - 39** - 25** 7* - 21** - 31** - 24** ns ns ns ns For age regressions: *P<0.05, **P<0.005 368 women, 320 men, aged 20-97 Riggs et al. J Bone Miner Res. 2004; 19:1945-54 Riggs et al. J Bone Miner Res. 2006; 21(2):315-23 17
    18. 18. 18 Age-related changes in trabecular microarchitecture • Decreased bone volume, trabecular thickness and number • Decreased connectivity • Decreased mechanical strength Image courtesy of David Dempster
    19. 19. 19 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
    20. 20. Theoretical effect of crossstruts on buckling strength # Horizontal Trabeculae Effective Length Buckling Strength 0 L S 1 1/2 L 4xS Bouxsein. Best Practice Res Clin Rheumatol, 2005; 19:897-911 20
    21. 21. 21 Cortical porosity increases with age 15 (41 iliac biopsies, age 19-90) r = 0.78 P < 0.001 12 (%) 4-fold increase in cortical porosity from age 20 to 80 9 6 Increased heterogeneity with age 3 0 0 20 40 60 Age (years) Brockstedt et al. Bone 1993; 14:681-91 80
    22. 22. 22 Age-related changes in femoral neck cortex and association with hip fracture Mayhew et al, Lancet 2005 20-year-old 80-year-old 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
    23. 23. 23 Age-related changes in bone properties associated with fracture risk • Decreased bone mass and BMD • Altered geometry • Altered architecture young – Cortical thinning – Cortical porosity – Trabecular deterioration elderly Images from L. Mosekilde, Technology and Health Care. 1998
    24. 24. 24 Outline • Determinants of bone strength • Age-related changes that contribute to femoral fragility • Interaction between skeletal loading and bone strength
    25. 25. Etiology of age-related fractures Loads applied to the bone FRACTURE? Bone strength 25
    26. 26. 26 The factor of risk concept Φ= Applied load Bone strength Φ > 1, Frx Φ < 1, no Frx • 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
    27. 27. 27 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?
    28. 28. 28 Independent risk factors for hip fracture 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
    29. 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 29
    30. 30. 30 Failure load (kN) Femur is strongest in habitual loading conditions 9 8 7 6 5 4 3 2 1 0 P < 0.001 7978 ± 700 N 2318 ± 300 N Stance Sideways fall Keyak et al. J Biomech. 1998; 31:125-33
    31. 31. 31 Failure load (kN) Femur is strongest in habitual loading conditions 9 8 7 6 5 4 3 2 1 0 Applied load Φ= Failure load Fall load P < 0.001 7978 ± 700 N 2318 ± 300 N Stance Sideways fall Keyak et al. J Biomech. 1998; 31:125-33 van den Kroonenberg et al. J Biomech. 1996; 29:807-11 Thus, Φ > 1 for sideways fall in elderly persons
    32. 32. 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. 33. 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. 34. 34 Factor of risk for vertebral fracture (L2) Bending forwards 90o with 10 kg weight in hands 1.8 Men 1.8 1.6 11.9% 1.4 1.6 1.4 1.2 1.0 0.8 0.8 0.6 0.6 0.4 0.4 0.2 0.0 +28% over life** 10 20 30 40 50 60 70 80 90 100 Age ** P<0.005 for age-regressions † 30.1% 1.2 1.0 Women p<0.01 for comparison of age-related change in M and W Bouxsein et al. J Bone Miner Res. 2006; 21:1475-82 0.2 +92% over life** † 0.0 10 20 30 40 50 60 70 80 90 100 Age
    35. 35. 35 Proportion of individuals with Φ > 1, per decade (Bending forwards 90 lifting 10 kg weight) o Incidence / 100,000 person-years 1400 1200 1000 800 600 400 200 0 30 40 50 60 70 60 90 53% 50 % 80 42% 40 27% 30 20 4% 10 0 20-29 30-39 40-49 Bouxsein et al. J Bone Miner Res. 2006; 21:1475-82 Age 11% 4% 11% 12% 50-59 60-69 70-79 21% 80+
    36. 36. 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. 37. 37 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 • Does not distinguish – – – – Specific attributes of 3D geometry Cortical vs cancellous density Trabecular architecture Intrinsic properties of bone matrix Bouxsein et al, 1999
    38. 38. 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. 39. 39 QCT assessment of bone density and geometry Images courtesy of Dr. Thomas Lang, UCSF
    40. 40. 40 Multi-detector computed tomography Non-Fx 62 yr Fx 62 yr Potential to show trabecular architecture… Higher resolution, but higher radiation dose Ito et al. J Bone Miner Res. 2005; 20:1828-36
    41. 41. 41 Trabecular architecture in vivo with high resolution pQCT ~ 80 µm3 voxel size Xtreme CT, Scanco ~ 3 min scan time, < 4 µSv Distal radius and tibia only Reproducibility: density: 0.7 - 1.5% * µ-architecture: 1.5 - 4.4% * * Boutroy et al. J Clin Endocrinol Metab. 2005; 90:6508-15
    42. 42. Tibia 42 Radius Premenopausal Postmenopausal Osteopaenia Postmenopausal Osteoporosis Postmenopausal Severe Osteoporosis Boutroy et al. J Clin Endocrinol Metab. 2005; 90:6508-15
    43. 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) % Difference 30% 26%* 20% 10% Spine BMD Fem Neck BMD 13%* BV/TV TbN TbTh 0% TbSp -0.3% 0.4% TbSpSD -5% -10% -9%* -12%* * p < 0.05 vs fracture free controls Boutroy et al. J Clin Endocrinol Metab. 2005; 90:6508-15 43
    44. 44. MRI for architecture assessment in vivo • Features of MRI – Non-invasive – No x-rays – True 3D – Oblique scanning plane Image courtesy of Dr. Felix Wehrli, UPenn – Clinical scanners – Image time: 12 - 15 minutes ~ 150 x 150 x 300 µm, 60 x 60 x 100 µm Image courtesy of Dr. Sharmila Majumdar, UCSF 44
    45. 45. 45 MRI assessment of trabecular structure Images from two women with similar BMD www.micromri.com
    46. 46. 46 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 Faulkner et al, Radiology 1991; Keyak et al, J Biomechanics 1998; Pistoia, Bone 2002; van Rietbergen JBMR 2003; Crawford et al, Bone 2003 Image courtesy of T. Keaveny Crawford et al, Bone 2003; 33: 744-750
    47. 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 47

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