MECHANICAL METRICS OF THE PROXIMAL FEMUR ARE PRECISE AND ASSOCIATED WITH HIP MUSCLE PROPERTIES: A MAGNETIC RESONANCE BASED FINITE ELEMENT STUDY

Proximal femoral (hip) fractures are a life-threatening injury which affects 30,000 Canadians annually. Improved muscle and bone strength assessment methods may reduce fracture occurrence rates in the future. Magnetic resonance (MR) imaging has potential to assess proximal femoral bone strength in vivo through usage of finite element (FE) modeling. Though, to precisely assess bone strength, knowledge of a technique’s measurement error is needed. Hip muscle properties (e.g., lean muscle and fat area) are intrinsically linked to proximal femoral bone strength; however, it is unclear which muscles and properties are most closely associated with bone strength. This thesis is focused on MR-based FE modeling (MR-FE) of the proximal femur and surrounding muscle properties (e.g., hip abductor fat area, hip extensor muscle area). The specific objectives of this research were 1) to characterize the short-term in vivo measurement precision of MR-FE outcomes (e.g., failure load) of the proximal femur for configurations simulating fall and stance loading, and 2) explore associations between upper thigh muscle and fat properties (e.g., hip abductor fat area, knee extensor muscle area) with MR-FE failure loads of the proximal femur. In vivo precision errors (assessed via root mean square coefficient of variation, CV%RMS from repeated measures) of MR-FE outcomes ranged from 3.3-11.8% for stress and strain outcomes, and 6.0-9.5% for failure loads. Hip adductor muscle area and total muscle area correlated with failure load of the fracture-prone neck and intertrochanteric region under both fall and stance loading (correlation coefficients ranged from 0.416-0.671). This is the first study to report the in vivo short-term precision errors of MR-FE outcomes at the proximal femur. Also, this is the first study to relate upper-thigh muscle and fat properties with MR-FE derived failure loads. Results indicate that MR-FE outcomes have comparable precision to computed tomography (CT) based FE outcomes and are related to hip muscle area

Finite Element Analysis of Bone and Experimental Validation

This chapter describes the application of the finite element (FE) method to bone tissues. The aspects that differ the most between bone and other materials’ FE analysis are the type of elements used, constitutive models, and experimental validation. These aspects are looked at from a historical evolution stand point. Several types of elements can be used to simulate similar bone structures and within the same analysis many types of elements may be needed to realistically simulate an anatomical part. Special attention is made to constitutive models, including the use of density-elasticity relationships made possible through CT-scanned images. Other more complex models are also described that include viscoelasticity and anisotropy. The importance of experimental validation is discussed, describing several methods used by different authors in this challenging field. The use of cadaveric human bones is not always possible or desirable and other options are described, as the use of animal or artificial bones. Strain and strain rate measuring methods are also discussed, such as rosette strain gauges and optical devices.publishe

A shape analysis approach to prediction of bone stiffness using FEXI

The preferred method of assessing the risk of an osteoporosis related fracture is currently a measure of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA). However, other factors contribute to the overall risk of fracture, including anatomical geometry and the spatial distribution of bone. Finite element analysis can be performed in both two and three dimensions, and predicts the deformation or induced stress when a load is applied to a structure (such as a bone) of defined material composition and shape. The simulation of a mechanical compression test provides a measure of whole bone stiffness (N mm−1). A simulation system was developed to study the sensitivity of BMD, 3D and 2D finite element analysis to variations in geometric parameters of a virtual proximal femur model. This study demonstrated that 3D FE and 2D FE (FEXI) were significantly more sensitive to the anatomical shape and composition of the proximal femur than conventional BMD. The simulation approach helped to analyse and understand how variations in geometric parameters affect the stiffness and hence strength of a bone susceptible to osteoporotic fracture. Originally, the FEXI technique modelled the femur as a thin plate model of an assumed constant depth for finite element analysis (FEA). A better prediction of tissue depth across the bone, based on its geometry, was required to provide a more accurate model for FEA. A shape template was developed for the proximal femur to provide this information for the 3D FE analysis. Geometric morphometric techniques were used to procure and analyse shape information from a set of CT scans of excised human femora. Generalized Procrustes Analysis and Thin Plate Splines were employed to analyse the data and generate a shape template for the proximal femur. 2D Offset and Depth maps generated from the training set data were then combined to model the three-dimensional shape of the bone. The template was used to predict the three-dimensional bone shape from a 2D image of the proximal femur procured through a DXA scan. The error in the predicted 3D shape was measured as the difference in predicted and actual depths at each pixel. The mean error in predicted depths was found to be 1.7mm compared to an average bone depth of 34mm. 3D FEXI analysis on the predicted 3D bone along with 2D FEXI for a stance loading condition and BMD measurement were performed based on 2D radiographic projections of the CT scans and compared to bone stiffness results obtained from finite element analysis of the original 3D CT scans. 3D FEXI provided a significantly higher correlation (R2 = 0.85) with conventional CT derived 3D finite element analysis than achieved with both BMD (R2 = 0.52) and 2D FEXI (R2 = 0.44)

Image Based Fracture Prediction Diagnostic Tool for Avascular Necrosis of the Femoral Head

Current methods to diagnose bone diseases like avascular necrosis (AVN) are subjective and a reliable assessment of the fracture risk is not available. A diagnostic fracture prediction tool would aid clinical diagnosis, anticipate disease progression and help with the planning of subsequent interventions. The strength of bones, including the femur, can be calculated using structural mechanics with a view to ascertaining fracture risk. The aim of this thesis was to develop and validate a fracture prediction method based tomographic imaging and beam theory. In-vitro disease models were created from additive manufacturing, explanted porcine and human femoral heads. The disease models contained a simulated lesion that was either lateral or medial to the fovea to analyse the effects of different lesion positions and to verify the ability of the developed fracture prediction tool. Current classification methods rely on the identification of the lesion volume and location to quantify the fracture risk, an approach that is purely based on geometrical information. The fracture prediction method based on structural stiffness also considered material properties which potentially added predictive capability. The tool was subsequently validated by predicting the fracture risk of femoral heads from AVN patients to demonstrate the ability to identify necrotic lesions that were likely to progress to fracture. The predicted fracture risk was compared to the current diagnostic gold standard to diagnose AVN. The beam tool was also compared against another novel fracture prediction tool based on FEA to identify possible advantages of beam theory. The verification tests confirmed that samples with a lesion in the weight bearing area were statistically more likely to fracture at a low load. A low fracture load meant a high fracture risk. However the experimental fracture load of porcine and human femoral heads, even among samples with similar lesions, showed variations indicating that lesion volume and location were not good predictors of fracture risk alone. There was a good correlation between the predicted fracture risk and in-vitro fracture loads of the human femoral head disease model indicating that the developed tool was able to objectively predict the fracture risk. The beam tool had similar good predictive capabilities as current diagnostic methods and fracture prediction methods based on FEA. An objective in-vivo analysis of the mechanical fracture risk helps identifying patients whose disease is at risk of progressing, as well as stratifying surgical interventions

Investigating the likelihood of pediatric femur fracture due to falls through finite element analysis.

Bone fracture is the second most common injury of child abuse. Studies have generally reported that femur fractures are more likely due to abuse than accidental causes in cases where the child is non-ambulatory. They have also found that household falls are commonly offered as the cause of injury in cases of abuse. In this study, a finite element (FE) pediatric femur model will be developed and used to evaluate likelihood of fracture in common household fall scenarios (bed falls and feet first falls). This will provide greater biomechanical evidence as to the likelihood of femur fracture due to common fall scenarios which may serve to better inform clinicians when assessing compatibility between stated cause and injury when household falls are reported. The purpose of this study is to determine the likelihood of fracture of a 12-month-old child’s femur due to commonly reported accidental fall scenarios using finite element analysis. Loading conditions in the FE model were derived from femur loads reported in a previously study measured using a 12-month old anthropomorphic test device (ATD) in experimentally simulated household falls. A FE femur model was derived from a CT scan performed on an 11-month old child. Validation of the FE model was conducted through mechanical testing of a bone surrogate printed using selective laser sintering of glass-fiber reinforced nylon. The finite element model used simple support for the constraints and the loads from the ATD study were applied at the corresponding location of the load cells, which bounded the diaphysis of the femur. The FE predicted outcomes including maximum principal stress and strain values were used to evaluate the likelihood of fracture by comparing to three different thresholds: (1) tensile yield strain, (2) ultimate tensile strength, and (3) ultimate flexural strength. Fifty-percent of bed falls exceeded the yield strain and ultimate tensile strength fracture threshold whereas only two (of 12) exceeded the flexural strength fracture threshold. Different bed fall dynamics considered resulted in a significant difference in peak strains while impact surface did not. Peak strains in bed falls were associated with the peak bending moment. No feet-first falls exceeded fracture thresholds. Fall height resulted in a significant difference in peak strains while the impact surface did not. Peak strains in feet-first falls were associated with the peak bending moment or torsional loads

Finite element modelling of healthy and osteoporotic bone

On a macro-structural level, the bones of the human skeleton is comprised mainly of trabecular (spongy) and cortical bone (dense). Trabecular bone typically occurs at the end points of long bones and has a structure described as a network of plates and rods. Cortical bone forms the hard outer shell and comprised mainly of osteons called Haversian systems. Bone is a composite material consisting mainly of an organic collagenous matrix ad carbonated apatite crystals. The structure of bone material is hierarchically organised and the inhomogeneous nature of bone material results in anisotropic mechanical properties. Bone adapts to its loading history and undergoes hypertrophy as result of increased loading and atrophy when loading is significantly reduced or completely removed. Osteoporosis is a disease of the bone which is characterised by loss of bone material and hence weakening of the bone. As a result of this, osteoporotic bone is more likely to fracture as a result of everyday loading. In this study three-dimensional finite element models of the shaft of the tibia were developed using the ABAQUS (Simula) finite element modelling programme. Models were developed to represent three symptoms of osteoporosis - bone thinning, low density and increased porosity. The models were subjected to compressive and torsional loading, and the stress distribution in response to these loads was analysed to gain an understanding of what areas of the tibia are at greatest risk of fracture and under what loading conditions. A risk of fracture for each of the elements was calculated and the maximum risk of fracture in each model gave an indication of fracture likelihood. This study found that osteoporotic bone showed increased stress and risk of fracture in both compression and torsion. However, torsion of bone with increased porosity was the only combination that produced results that indicate the occurrence of fracture. The aim is for the bone models developed in this study to be used clinically to reduce fracture occurrence in patients with osteoporotic bone loss.On a macro-structural level, the bones of the human skeleton is comprised mainly of trabecular (spongy) and cortical bone (dense). Trabecular bone typically occurs at the end points of long bones and has a structure described as a network of plates and rods. Cortical bone forms the hard outer shell and comprised mainly of osteons called Haversian systems. Bone is a composite material consisting mainly of an organic collagenous matrix ad carbonated apatite crystals. The structure of bone material is hierarchically organised and the inhomogeneous nature of bone material results in anisotropic mechanical properties. Bone adapts to its loading history and undergoes hypertrophy as result of increased loading and atrophy when loading is significantly reduced or completely removed. Osteoporosis is a disease of the bone which is characterised by loss of bone material and hence weakening of the bone. As a result of this, osteoporotic bone is more likely to fracture as a result of everyday loading. In this study three-dimensional finite element models of the shaft of the tibia were developed using the ABAQUS (Simula) finite element modelling programme. Models were developed to represent three symptoms of osteoporosis - bone thinning, low density and increased porosity. The models were subjected to compressive and torsional loading, and the stress distribution in response to these loads was analysed to gain an understanding of what areas of the tibia are at greatest risk of fracture and under what loading conditions. A risk of fracture for each of the elements was calculated and the maximum risk of fracture in each model gave an indication of fracture likelihood. This study found that osteoporotic bone showed increased stress and risk of fracture in both compression and torsion. However, torsion of bone with increased porosity was the only combination that produced results that indicate the occurrence of fracture. The aim is for the bone models developed in this study to be used clinically to reduce fracture occurrence in patients with osteoporotic bone loss

Cortical thickness estimation of the proximal femur from multi-view dual-energy X-ray absorptiometry

Hip fracture is the leading cause of acute orthopaedic hospital admission amongst the elderly, with around a third of patients not surviving one-year post-fracture. Current risk assessment tools ignore cortical bone thinning, a focal structural defect characterizing hip fragility. Cortical thickness can be measured using computed tomography, but this is expensive and involves a significant radiation dose. Dual-energy X-ray absorptiometry (DXA) is the preferred imaging modality for assessing fracture risk, and is used routinely in clinical practice. This thesis proposes two novel methods which measure the cortical thickness of the proximal femur from multi-view DXA scans. First, a data-driven algorithm is designed, implemented and evaluated. It relies on a femoral B-spline template which can be deformed to fit an individual’s scans. In a series of experiments on the trochanteric regions of 120 proximal femurs, the algorithm’s performance limits were established using twenty views in the range 0° – 171°: estimation errors were 0.00 ± 0.50 mm. In a clinically viable protocol using four views in the range −20° to 40°, measurement errors were −0.05 ± 0.54 mm. The second algorithm accomplishes the same task by deforming statistical shape and thickness models, both trained using Principal Component Analysis (PCA). Three training cohorts are used to investigate (a) the estimation efficacy as a function of the diversity in the training set and (b) the possibility of improving performance by building tailored models for different populations. In a series of cross-validation experiments involving 120 femurs, minimum estimation errors were 0.00 ± 0.59 mm and −0.01 ± 0.61 mm for the twenty- and four-view experiments respectively, when fitting the tailored models. Statistical significance tests reveal that the template algorithm is more precise than the statistical, and that both are superior to a blind estimator which naively assumes the population mean, but only in regions of thicker cortex. It is concluded that cortical thickness measured from DXA is unlikely to assist fracture prediction in the femoral neck and trochanters, but might have applicability in the sub-trochanteric region.This work was funded by the W. D. Armstrong Trust Fun

Characterisation of disuse-related osteoporosis in an animal model of spinal cord injury

Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected.Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected