Mechanical and morphometric characterization of cancellous bone

[EN] Bone fracture is a social health problem of increasing magnitude because of its prevalence in aged population due to osteoporosis. Bone quality is often characterized by bone mineral density (BMD) measured at cancellous bone regions using dual-energy X-ray absorptiometry (DXA). However, BMD alone cannot predict several cases because not only density is important, but also microstructure plays an important role in cancellous bone strength. The mechanical properties can be used as indicators of bone integrity as a function of age, disease or treatment. Therefore, cancellous bone fracture characterization and its relationship to microstructure has not been completely solved in the literature and is relevant to improve fracture prediction. In this thesis, we aim at characterizing cancellous bone morphometry and mechanical behavior. Morphometry is estimated through the analysis of micro-computed tomography (micro-CT) images of vertebral cancellous bone specimens. With regards to the mechanical behavior, we calculate elastic, yield and failure properties at the apparent and tissue levels. To determine them, we followed different approaches: compression tests, finite element models and micro-CT phantoms. We have developed finite element models that reproduce the elastic and failure response of cancellous bone under compression conditions. We modeled failure as a combination of continuum damage mechanics and the element deletion technique. The numerical models permitted to estimate elastic and failure properties. Failure properties were consistent with results reported in the literature. Specifically, our results revealed that yield strain is relatively constant (0.7 %) over a range of apparent densities, while failure strain presents a wider range of variation. A single strain parameter (equivalent strain) was found as an accurate descriptor of cancellous bone compression failure. Image-based numerical models usually need for the action of a technician to segment the images. Therefore, we studied the sensitivity to variations of the segmentation threshold on the morphometry and the elastic properties of vertebral cancellous bone specimens of different bone volume fractions. The apparent modulus is highly sensitive to the segmentation threshold. We report variations between 45 and 120 % for a ± 15 % threshold variation. Other parameters, such as BS/BV, BS/TV, Tb.Sp, Tb.N, Conn.D and fractal dimension were influenced significantly. Digital image correlation (DIC) was applied to images taken during compression testing to analyze displacement fields at failure and characterize them. Some variables were explored to describe failure and a study is done about how DIC parameters influence the strain field obtained. Facet and step sizes have a relevant effect on the failure strain estimation, and an increment of both parameters reduces the strain estimation up to 40 %. Besides, several parameters combination led to correct failure pattern detection, so values reported in the literature should be referred to the parameters used. Furthermore, we explored if cancellous bone microstructure acts (non-speckle/texture approach) as a proper pattern to calculate displacements using DIC technique. As regards relationships between microstructure and mechanics, single and multiple parameter analysis were performed to assess the morphometric variables that control the explanation of mechanical properties variation. Bone volume fraction (BV/TV), bone surface to volume ratio (BS/BV), mean trabecular thickness (Tb.Th) and fractal dimension (D) presented the best linear correlations to the elastic properties, while both the yield and failure strains did not show correlation to any morphometric parameter. The regressions obtained permit to estimate those mechanical properties that describe the state of a specimen.[ES] Las fracturas óseas constituyen un problema social de salud con magnitud creciente por su prevalencia en la población de edad avanzada debido a la osteoporosis. La calidad del hueso suele caracterizarse mediante la estimación de la densidad mineral ósea (DMO) en regiones de hueso trabecular, utilizando absorciometría de rayos X de energía dual (DXA). No obstante, la DMO por si sola no es capaz de predecir numerosos casos de fractura porque no solo importa la pérdida de densidad, sino que la microestructura también tiene un papel principal en la resistencia del hueso. Las propiedades mecánicas del hueso pueden usarse como indicadores de su integridad en función de la edad, enfermedad o tratamiento. Por lo tanto, la caracterización de la fractura de hueso trabecular y su relación con la microestructura no se ha resuelto de forma completa en la literatura y es relevante para mejorar las predicciones de fractura. En esta tesis, nuestro principal objetivo es caracterizar la morfometría y el comportamiento mecánico del hueso trabecular. Estimamos la morfometría a través del análisis de imágenes obtenidas por micro tomografía computerizada (micro-CT) de muestras de hueso trabecular vertebral de cerdo. Respecto al comportamiento mecánico, calculamos propiedades elásticas, de plasticidad y fractura a escala aparente y de tejido. Para determinar esas propiedades, hemos seguido diferentes procedimientos: ensayos a compresión, modelos de elementos finitos y fantomas de calibración micro-CT. Los modelos de elementos finitos desarrollados reproducen la respuesta elástica y de fallo bajo condiciones de compresión en hueso trabecular, modelando el fallo como combinación de mecánica del daño contínuo y la técnica de eliminación de elementos. Los modelos numéricos desarrollados han permitido estimar propiedades elásticas y de fallo. En concreto, las deformaciones de inicio de fallo estimadas son relativamente constantes para las muestras analizadas (0.7 %), mientras que las deformaciones últimas de fallo presentan un rango de variación mayor. Por otro lado, encontramos que la deformación equivalente es el descriptor más preciso del fallo a compresión del hueso trabecular. Normalmente, los modelos numéricos basados en imágenes suelen necesitar la acción de un técnico para segmentar las imágenes. En este sentido, estudiamos la sensibilidad de la morfometría y la estimación de propiedades elásticas ante variaciones en el umbral de segmentación en muestras con distinta fracción en volumen. Hemos obtenido que la rigidez aparente es muy sensible a cambios en el umbral de segmentación, con variaciones entre 45 y 120 % para una variación de ± 15 % del umbral de segmentación. Otros parámetros, como BS/BV, BS/TV, Tb.Sp, Tb.N, Conn.D y la dimensión fractal se ven afectados significativamente. Por otro lado, hemos aplicado la técnica correlación digital por imagen (DIC) para caracterizar campos de desplazamientos en el fallo a compresión del hueso trabecular, a partir del análisis de imágenes tomadas durante el ensayo de las muestras. Además, estudiamos la influencia de algunos parámetros de la técnica DIC en el campo de deformaciones obtenido. También, hemos explorado la aplicación DIC sin el uso de moteado, utilizando como patrón de reconocimiento la propia microestructura trabecular. En relación al estudio de la influencia de la microestructura en la respuesta mecánica, hemos calculado correlaciones de uno y varios parámetros para analizar qué variables morfométricas explican la variación de las propiedades mecánicas. La fracción en volumen de hueso (BV/TV), la relación entre el área y el volumen de hueso (BS/BV), el espesor trabecular medio (Tb.Th) y la dimensión fractal (D) presentan las mejores correlaciones lineales respecto a las propiedades elásticas, mientras que las deformaciones de inicio de plasticidad y fractura no mostraron correlación con ningún parámetro morfométrico.[CA] Les fractures òssies constitueixen un problema social de salut amb magnitud creixent per la seua prevalença en la població d'edat avançada a causa de l'osteoporosi. La qualitat de l'os sol caracteritzar-se mitjançant l'estimació de la densitat mineral òssia (DMO) en regions d'os trabecular, utilitzant absorciometria de raigs X d'energia dual (DXA). No obstant això, la DMO per si sola no és capaç de predir nombrosos casos de fractura perquè no sols importa la pèrdua de densitat, sinó que la microestructura també té un paper principal en la resistència de l'os. Les propietats mecàniques de l'os poden usar-se com a indicadors de la seua integritat en funció de l'edat, malaltia o tractament. Per tant, la caracterització de la fractura d'os trabecular i la seua relació amb la microestructura no s'ha resolt de manera completa en la literatura i és rellevant per a millorar les prediccions de fractura. En aquesta tesi, el nostre principal objectiu és caracteritzar la morfometria i el comportament mecànic de l'os trabecular. Estimem la morfometria a través de l'anàlisi d'imatges obtingudes per micro tomografia automatitzada (micro-CT) de mostres d'os trabecular vertebral de porc. Respecte al comportament mecànic, calculem propietats elàstiques, de plasticitat i fractura a escala aparent i de teixit. Per a determinar aqueixes propietats, hem seguit diferents procediments: assajos a compressió, models d'elements finits i fantomas de calibratge micro-CT. Hem desenvolupat models d'elements finits que reprodueixen la resposta elàstica i de fallada sota condicions de compressió en os trabecular, modelant la fallada com a combinació de mecànica del dany continu i la tècnica d'eliminació d'elements. Els models numèrics desenvolupats han permés estimar propietats elàstiques i de fallada. Les nostres estimacions respecte a propietats de fallada són consistents amb valors reportats en la literatura. En concret, les deformacions d'inici de fallada estimades són relativament constants per a les mostres analitzades (0.7 %), mentre que les deformacions últimes de fallada presenten un rang de variació major. D'altra banda, trobem que la deformació equivalent és el descriptor més precís de la fallada a compressió de l'os trabecular. Els models numèrics basats en imatges solen necessitar l'acció d'un tècnic per a segmentar les imatges. En aquest sentit, estudiem la sensibilitat de la morfometria i l'estimació de propietats elàstiques davant variacions en el llindar de segmentació en mostres amb diferent fracció en volum. Hem obtingut que la rigidesa aparent és molt sensible a canvis en el llindar de segmentació, amb variacions entre 45 i 120 % per a una variació de ± 15 % del llindar de segmentació. Altres paràmetres, com BS/BV, BS/TV, Tb.Sp, Tb.N, Conn.D i la dimensió fractal es veuen afectats significativament. D'altra banda, hem aplicat la tècnica correlació digital per imatge (DIC) per a caracteritzar camps de desplaçaments en la fallada a compressió de l'os trabecular, a partir de l'anàlisi d'imatges preses durant l'assaig de les mostres. A més, estudiem la influència d'alguns paràmetres de la tècnica DIC en el camp de deformacions obtingut. També, hem explorat l'aplicació DIC sense l'ús de clapejat, utilitzant com a patró de reconeixement la pròpia microestructura trabecular. En relació a l'estudi de la influència de la microestructura en la resposta mecànica, hem calculat correlacions d'un i diversos paràmetres per a analitzar quines variables morfomètriques expliquen la variació de les propietats mecàniques. La fracció en volum d'os (BV/TV), la relació entre l'àrea i el volum d'os (BS/BV), la espessor trabecular mitjà (Tb.th) i la dimensió fractal (D) presenten les millors correlacions lineals respecte a les propietats elàstiques, mentre que les deformacions d'inici de plasticitat i fractura no van mostrar correlació amb cap paràmetre morfomètric.Belda González, R. (2020). Mechanical and morphometric characterization of cancellous bone [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/149376TESI

Animal experiment (rabbit) to demonstrate changes in trabecular bone mechanical properties over time using finite element analysis.

Decreased strength of trabecular bone is a direct effect of osteoporosis, which can be evaluated by finite element analysis. However, computational limitations have restricted previous trabecular bone analyses primarily to the linear domain. In addition, previous work was largely invasive and the corresponding finite element models were typically homogeneous. Nonlinear heterogeneous finite element analysis was used to calculate trabecular bone apparent strength directly from in vivo micro computational tomography (micro-CT) scans. Through a series of validation experiments, it was shown that this nonlinear modeling is more accurate in evaluating trabecular bone mechanics in osteoporosis than previous work. A parameter driven set of material properties was employed in the finite element models using gray levels in the form of Hounsfield units as the independent variable. This enabled the finite element models to capture the variations of material properties of trabecular bone. The methods and techniques for converting the micro-CT scans into finite element models, defining the finite element models (element type, material properties characteristics) and solving the models are discussed in detail. In addition, the techniques developed for image preprocessing, such as image registration and image degradation, are also provided in this dissertation. The scanning, image processing and modeling methods and techniques were applied to two groups of rabbits, an ovariectomy group and a control group, to evaluate the time-course of trabecular bone osteoporosis. Our experiment showed that ovariectomy significantly slows the normal bone strength increase over time observed in the control group. The strength increase over time was due to a combination of increased bone architecture indices such as volume fraction and trabecular thickness as well as increased material properties due to greater bone tissue density. Compared to heterogeneous models, the homogeneous models reflected less strength increase over time because they lack the capability to capture tissue level material property variations. Volume fraction analysis alone resulted in even lower predicted increases in bone strength because it could only monitor the bone apparent level density variation. Thus the nonlinear heterogeneous models, with parameter driven material definitions, are more accurate than other types of models or methods

Simulation of fracture strength improvements of a human proximal femur using finite element analysis.

The most common hip fracture in the elderly occurs as a result of a fall to the side with impact over the greater trochanter resulting in a fracture of the proximal femur. The fracture usually involves the femoral neck or the intertrochanteric region. It has recently been determined that the fracture crack of a hip fracture typically initiates on the superior-lateral cortex of the femoral neck and then propagates across the femoral neck, resulting in a complete fracture. The strength of the superior-lateral cortex of the femoral neck is likely determined by the combined properties of the generally thin cortex (outer layer) and the underlying trabecular bone in this region. The objective of this study was to determine the relative effects of increasing or decreasing the thickness of these bone tissues on the overall failure strength of the proximal femur. The clinical significance of this work relates to hip fracture risk with various potential treatment options to improve either cortical or trabecular bone quality. A human femur obtained from a 68 year old female donor was scanned using computed tomography at 60-micron voxel resolution and a series of high-resolution finite element models were generated. The models were constructed with a base-element dimension of 120 microns and models included a basic model with cortical and trabecular thicknesses representative of the cadaver specimen from the original scan. Other models used a standardized algorithm to either dilate or erode the trabecular and cortical bone compartments of the femoral neck so that a total of nine models were created including the basic model. Each model was used to simulate a fall-to-the-side loading condition with appropriate boundary and loading conditions as used in previous models and experiments. An experimental test of the cadaver femur was also performed with three strain gauges placed on the proximal femur: on the superior-lateral cortex, on the inferior-medial cortex, and on the medial cortex positioned distal to the lesser trochanter. This femur was loaded at a rate of 100 mm/s until fracture of the femoral neck using a standard fall-to-the-side setup and the applied load and gauge strains were recorded. The femur neck fractured at a load of 2140 N. To validate the basic finite element model, the strain gauge strains at the load levels of 1000 N and 2000 N were compared to the calculated strains from the basic model at the same loads and same location as the gauge on the cadaver femur. After the basic model was validated, a failure criterion was determined as the volume percentage of the elements in the model that had exceeded 7000 µε at the failure load corresponding to the load at which the cadaver femur failed. Subsequently, this failure criterion was applied to the other eight models as a parametric analysis to estimate the increase or decrease in failure strength caused by the changes in cortical and trabecular thickness. The validation test results showed that the basic finite element model calculated strain on the superolateral cortex was within 2.1% of the experimentally measured strain at 1000 N loading. The validated basic model was then used to determine that the percentage of finite elements (by volume of the model) in excess of 7000 µε at the failure load was 4.2%. This failure criterion was then used to estimate the failure load for the other eight models with different combinations of either thicker (+120 µm) or thinner (-120 µm) cortex and trabeculae in the femoral neck. The calculated failure loads ranged from 324 N for the model with thinned cortex and thinned trabeculae to 3336 N for the model with thickened cortex and thickened trabeculae. The model with normal cortex and thickened trabeculae had a failure load of 3242 N, which is only 2.8% less than the strongest case. The largest single parameter effect on proximal femoral strength is realized by an increase in trabecular thickness. This is somewhat surprising considering that cortical bone is typically stronger than cancellous bone. However, the spatial arrangement of trabecular bone and the buttress support it provides to the thin cortex apparently plays an important role in the ability of a global increase in thickness to have a significant beneficial effect

3-D visualization and prediction of spine fractures under axial loading

Thesis (Ph.D.)--Boston UniversityVertebral fractures are the hallmark of osteoporosis, yet the failure mechanisms involved in these fractures are not well understood. Current approaches to predicting fracture risk rely on average measures of bone mineral density in the vertebra, which are imperfect predictors of vertebral strength and poor predictors of fracture risk. Prior research has established that substantial regional variations in density exist throughout the vertebra and has suggested several biomechanical consequences of these variations. The overall goal of this dissertation was to characterize failure mechanisms in human vertebrae, with specific emphasis on the role of intra-vertebral heterogeneity in density and microstructure and on identifying clinically feasible techniques for predicting fracture risk. Using images obtained from micro-computed tomography (μCT) and quantitative computed tomography (QCT), the intra-vertebral heterogeneity in bone density was quantified in cadaveric specimens. Quantitative measures of this heterogeneity improved predictions of vertebral strength as compared to predictions based only on mean density. Subsequently, the intra-vertebral heterogeneity in density was measured via QCT in a cohort of post-menopausal women and was found to be lower in those who had sustained a vertebral fracture vs. in age-matched individuals without fracture. The next set of studies focused on assessing the accuracy of finite element (FE) models for predicting vertebral failure. Digital volume correlation (DVC) was used to measure the deformations sustained throughout the vertebra during compression tests. These results were compared against deformation patterns predicted using FE models created from QCT images of the vertebrae. Good agreement was found between predicted and measured deformations when the boundary conditions were accurately defined, despite simplifications made in representing material properties. The outcomes from this dissertation demonstrate that the intra-vertebral heterogeneity in density contributes to bone strength and has promise as a clinically feasible indicator of fracture risk. OCT-based FE models, which by definition account for this heterogeneity, are another promising technique, yet will likely require non-invasive techniques for estimating vertebral loading to provide the requisite accuracy in failure predictions. These two engineering approaches that account for the spatial heterogeneity in density within the vertebra may lead to more sensitive and specific indicators of fracture risk

Design and development of a multiscale model for the osteoporotic fracture prevention: a preclinical tool

Se espera que la osteoporosis sea partícipe de más de 9 millones de nuevas fracturas en todo el mundo en un futuro no muy lejano, ya que es una de las enfermedades con mayor índice de impacto entre la población de los países desarrollados. Se define como una enfermedad sistémica caracterizada por la pérdida de masa ósea y una alteración de su microestructura interna con la consiguiente susceptibilidad a la fractura. Actualmente, la estimación del riesgo de fractura se lleva a cabo mediante tomografía axial computerizada (TAC), Rayos X o densitometrías. Sin embargo, las simulaciones por elementos finitos para un paciente determinado, pueden contener una gran cantidad de información que permitirían unas predicciones más precisas. Una metodología multiescala ayudaría al desarrollo y caracterización de modelos de fractura más robustos que permitirían conocer de una manera más detallada el comportamiento del hueso. Además, dichos modelos podrían incorporar parámetros relacionados con la edad, el grado de osteoporosis o el tratamiento mediante fármacos. De hecho, debido a que el hueso trabecular interviene, en gran medida, en las fracturas de cadera osteoporóticas, un tratamiento preventivo alternativo para reducir el riesgo de fractura osteoporótica consistiría en la inyección de cemento óseo (PMMA) en el fémur osteoporótico.Por lo tanto, el principal objetivo de esta tesis doctoral es el desarrollo de un modelo multiescala para la prevención de la fractura ósea osteoporótica. Este modelo nos permitirá conocer más acerca de los mecanismos de fallo asociados a la osteoporosis desde el nivel tisular hasta el nivel macroscópico a fin de evaluar la factibilidad de la femoroplastia. Para alcanzar este objetivo, en primer lugar, se ha llevado a cabo una caracterización in vitro e in silico de estructuras artificiales de hueso artificial, denominadas open-cell (Sawbones, Malmö, Sweden), con propiedades próximas al hueso sano y osteoporótico, de manera que permita elucidar mecanismos de fractura asociados a la osteoporosis desde el nivel tisular. De esta manera, se han empleado métodos experimentales y computacionales basados en el procesado de imagen con el fin de estimar el módulo elástico y las porosidades de las diferentes estructuras open-cell. Las resultados computacionales y experimentales fueron comparados con los datos aportados por el fabricante. Se apreciaron importantes diferencias no sólo en términos del módulo de Young sino también en las porosidades. Posteriormente, se desarrolló un modelo discreto de partículas basado en la Teoría del Movimiento Aleatorio para simular la infiltración de cemento a través de las estructuras open-cell, previamente caracterizadas. Los parámetros del modelo incluyeron no sólo la viscosidad del cemento (alta o baja) sino la dirección de inyección (vertical o diagonal). De nuevo, se llevó a cabo una caracterización in vitro e in silico de las estructuras cementadas, validando el modelo computacional mediante ensayos experimentales. Dichos resultados mostraron que el modelo discreto de partículas era suficientemente robusto para su aplicación en la escala macroscópica. También, se inyectó cemento in vivo en fémures de conejo a fin de evaluar la factibilidad de la femoroplastia. Finalmente, se utilizaron fémures sanos y osteoporóticos para la predicción computacional del grado de mejora de las propiedades mecánicas cuando se inyectaba cemento de alta o baja viscosidad. El cemento de baja viscosidad mejoraba notablemente las cargas de fractura con respecto a los fémures no cementados. Los resultados finales mostraron que el cemento óseo mejora definitivamente las propiedades del hueso osteoporótico y la metodología propuesta puede llegar a utilizarse como una herramienta preclínica para un diagnóstico más preciso.<br /

RELATIONSHIPS OF LONG-TERM BISPHOSPHONATE TREATMENT WITH MEASURES OF BONE MICROARCHITECTURE AND MECHANICAL COMPETENCE

Oral bisphosphonate drug therapy is a common and effective treatment for osteoporosis. Little is known about the long-term effects of bisphosphonates on bone quality. This study examined the structural and mechanical properties of trabecular bone following 0-16 years of bisphosphonate treatment. Fifty-three iliac crest bone samples of Caucasian women diagnosed with low turnover osteoporosis were identified from the Kentucky Bone Registry. Forty-five were treated with oral bisphosphonates for 1 to 16 years while eight were treatment naive. A section of trabecular bone was chosen from a micro-computed tomography (Scanco µCT 40) scan of each sample for a uniaxial linearly elastic compression simulation using finite element analysis (ANSYS 14.0). Morphometric parameters (BV/TV, SMI, Tb.Sp., etc.) were computed using µCT. Apparent modulus, effective modulus and estimated failure stress were calculated. Biomechanical and morphometric parameters improved with treatment duration, peaked around 7 years, and then declined independently of age. The findings suggest a limit to the benefits associated with bisphosphonate treatment and that extended continuous bisphosphonate treatment does not continue to improve bone quality. Bone quality, and subsequently bone strength, may eventually regress to a state poorer than at the onset of treatment. Treatment duration limited to less than 7 years is recommended

The Role of Architecture and Tissue Properties in the Structural Integrity of Human Vertebral Cancellous Bone

Age-related disorders of bone metabolism like osteoporosis may compromise structural integrity of bone and result in fragility fractures, particularly at cancellous bone sites. Several factors contribute to cancellous bone strength, including bone density, architecture, and material properties. Clinical assessment of bone density using dual-energy X-ray absorptiometry (DXA), which is somewhat distorted by the fan-shaped X-ray beam, does not fully account for fracture incidence and only partially correlates with bone strength. Spatial variations in trabecular architecture captured by micro-computed tomography (microCT) have been related to structural behavior using microstructure-based models. However, the impact of material variations is not well understood and should be investigated. DXA fan-beam magnification was quantified by scanning aluminum rods at several distances above the X-ray source. Projected area and bone mineral content decreased by 1.6-1.8% per centimeter distance above the source, indicating that changes in girth over time would artificially reduce DXA measurements and obscure actual gains associated with growth or interventions. The ability of DXA to predict bone architecture and material properties was assessed in thoracolumbar specimens from 21 cadavers. T11-L4 was scanned using DXA, and cancellous bone cores drilled from the center of T12 and L2 were scanned at 17 microns using microCT and then compressed uniaxially to failure. DXA and microCT bone mass correlated similarly with cancellous bone stiffness and strength in females but not males. DXA could not account for variations in architecture detected by microCT, particularly in the thoracic spine, for either males or females. MicroCT scans may better assess bone strength in the thoracic spine and could replace DXA scans altogether if measurements could be made non-invasively, accurately, and affordably. Spatial variations in architecture and material properties were examined with architecture- and material-based finite element (FE) models developed from microCT scans. Homogeneous and heterogeneous material models were examined. FE models were improved by heterogeneity, whether between subjects using specimen-specific uniform properties or within subjects using spatially varying properties. Apparent stiffness was the same for specimen-specific models, regardless of variations in tissue modulus. The mean tissue modulus, rather than its distribution, appears to drive the overall mechanical behavior for vertebral cancellous bone

On prediction of the compressive strength and failure patterns of human vertebrae using a quasi-brittle continuum damage finite element model

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Mapping Trabecular Bone Fabric Tensor by in Vivo Magnetic Resonance Imaging

The mechanical competence of bone depends upon its quantity, structural arrangement, and chemical composition. Assessment of these factors is important for the evaluation of bone integrity, particularly as the skeleton remodels according to external (e.g. mechanical loading) and internal (e.g. hormonal changes) stimuli. Micro magnetic resonance imaging (µMRI) has emerged as a non-invasive and non-ionizing method well-suited for the repeated measurements necessary for monitoring changes in bone integrity. However, in vivo image-based directional dependence of trabecular bone (TB) has not been linked to mechanical competence or fracture risk despite the existence of convincing ex vivo evidence. The objective of this dissertation research was to develop a means of capturing the directional dependence of TB by assessing a fabric tensor on the basis of in vivo µMRI. To accomplish this objective, a novel approach for calculating the TB fabric tensor based on the spatial autocorrelation function was developed and evaluated in the presence of common limitations to in vivo µMRI. Comparisons were made to the standard technique of mean-intercept-length (MIL). Relative to MIL, ACF was identified as computationally faster by over an order of magnitude and more robust within the range of the resolutions and SNRs achievable in vivo. The potential for improved sensitivity afforded by isotropic resolution was also investigated in an improved µMR imaging protocol at 3T. Measures of reproducibility and reliability indicate the potential of images with isotropic resolution to provide enhanced sensitivity to orientation-dependent measures of TB, however overall reproducibility suffered from the sacrifice in SNR. Finally, the image-derived TB fabric tensor was validated through its relationship with TB mechanical competence in specimen and in vivo µMR images. The inclusion of trabecular bone fabric measures significantly improved the bone volume fraction-based prediction of elastic constants calculated by micro-finite element analysis. This research established a method for detecting TB fabric tensor in vivo and identified the directional dependence of TB as an important determinant of TB mechanical competence