Weak and osteoporotic bones are an increasing cause of mortality and painful physical impairment among the elderly, especially in the Western world. Bone mineral density (BMD, g/cm2) accrual during childhood and adolescence is thought to influence an individual’s risk of osteoporosis and the related fractures. A main aim of this thesis is to investigate the effects that various types of weight-bearing physical activity have on bone accretion in young males during their active sports careers and to study the effects that detraining has on BMD. The results suggest that bone is sensitive to loading after puberty in males, and important gains in BMD stemming from physical activity were observed during the 12-year follow-up period (papers I-III). These gains seem to be site-specific and related to the type and amount of physical activity in which individuals participate (papers I-III). For example, badminton, a sport that is characterized by jumps and rapid versatile moments in multiple directions was associated with greater gains in BMD than ice hockey was. In addition, our results indicate that with reduced training, exercise-induced bone benefits decline, predominantly at trabecular sites (paper II). In contrast, high bone density attained from previous physical loading was partially preserved at cortical bone sites after about eight years of reduced activity (papers I-II). In study IV, the associations between self-perceived health, BMD, and other lifestyle factors were studied in a well-defined group of women and men of varying ages. We found that self-perceived health was related to several lifestyle factors, such as physical activity, which were also related to BMD at the femoral neck. In summary, BMD in young males seem to be especially sensitive to activities associated with supposed high strains in unusual directions at specific bone sites. A high bone density stemming from previous weight-bearing physical activity is largely lost at trabecular bone sites with reduced physical activity levels. Finally, self-perceived health seems to be associated with several lifestyle factors that are also associated with BMD at the femoral neck.

The results of total knee arthroplasty are inferior in younger patients. The challenge today is therefore to develop designs and concepts that will last at least 25 years. This thesis has evaluated the fixation to bone of modern designs of knee prostheses uring RSA analysis. Coating implant surfaces with hydroxy-apatite have proven to enhance fixation to bone. Addition of screws for fixation of the tibial component enhances the fixation, but has negative side effects such as osteolysis around the screws, in turn leading to a higher risk of component loosening. The magnitude and pattern of migration was studied in a randomized study of uncemented tibial implants coated with hydroxy-apatite with and without additional screw fixation in patients younger than 65 years. The uncemented implants migrated initially more than the cemented implants that constituted the control group. Both uncemented groups stabilized at 3 monthes with no further migration, while the cemented implants showed a continuous migration up to the 2 year follow-up, indicating continuous bone resorption at the implant-bone interface, a fact that might lead to an increased risk of late implant loosening. This may not be a problem in older patients, but may have consequences for long-term fixation in younger patients. There was no difference between the two uncemented groups indicating that screws do not improve fixation. Hydroxy-apatite coated knee implants might be well suited for younger patients. Mobile bearing total knee arthroplasty theoretically uncouples the forces at the implant-bone interface, thus improving fixation of the implant to bone. The magnitude and pattern of migration of a cemented mobile bearing knee arthroplasty and a fixed bearing total knee arthroplasty was compared in a randomized study. The results showed that mobile bearings did not improve fixation. Trabecular metal, a new material recently introduced for total knee arthroplasty, has several theoretical advantages. Trabecular metal tibial implants were evaluated in a randomized study in patients younger than 60 years. The implants displayed the typical migration pattern for uncemented implants with greater migration initially followed by early stabilization. The majority of the trabecular metal implants subsided into the bone with no lift-off. Lift-off has the potential of exposing the interface to joint fluid with the potential risk of bone resorption and late loosening, and is commonly seen in metal-backed implants. The finding of absence of lift-off is regarded beneficial for uncemented fixation. Trabecular metal tibial implants might be suited for younger patients. The optimal mode of fixation of the femoral component is yet to be established. Comparing cemented femoral components with uncemented femoral components in a randomized study in patients younger than 60 years revealed no differences of the magnitude or the pattern of migration. Uncemented femoral component seems equally as good as cemented components in younger patients.

Aquaporin proteins significantly increase water permeability across tissues and cell membranes. Ocular tissues, including the trabecular meshwork (TM) and retinal pigment epithelium (RPE), are especially reliant on aquaporin mediated water movement for ocular homeostasis. Even though bulk fluid movement is paracellular through the TM and transcellular through the RPE, both express aquaporin-1 (AQP1). The role and regulation of AQP1 as it relates to homeostasis in different ocular tissues is not well understood. I hypothesized that ocular tissues respond to external mechanical and molecular cues by altering AQP1 expression and function in order to regulate ocular fluid movement and maintain homeostasis.To test how AQP1 function is altered in response to external cues in order to maintain tissue-specific homeostasis, I addressed the following two aims. The first aim was directed at determining how mechanical strain, an external stimulus that routinely affects TM function, influences AQP1 expression and TM homeostasis. Primary cultures of human TM were subjected to static and cyclic stretch and then analyzed for changes in AQP1 expression by western blot and cell damage by activity of lactate dehydrogense (LDH) in conditioned media. The results show AQP1 expression and LDH release significantly increased with static stretch. Analysis of LDH release with respect to AQP1 expression revealed an inverse linear relationship (r² = 0.7780).The second aim was directed at characterizing signaling mechanisms responsible for regulating fluid transport in RPE, previously shown to be dependent upon AQP1. I treated primary cultures of human RPE with either atrial natriuretic peptide (ANP) or 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP) in the presence or absence of Anantin (ANP-receptor inhibitor) or H-8 (Protein Kinase G inhibitor). The results show that ANP and 8-Br-cGMP significantly increased apical to basal net fluid movement (p < 0.05, n = 3). Inhibition of these effects was successful with Anantin treatment but not with application of H-8.The data presented demonstrate a novel role of protection for AQP1 in TM, and also expand upon cGMP dependent regulation of RPE fluid transport. The combined studies indicate tissue specific AQP1 regulation may offer new avenues to target water movement in treatment of ocular pathologies.

In vivo, biomechanical stress plays an important role in tissue physiology and pathology, affecting cell and tissue behavior. Even though conventional outflow tissues in the eye are constantly exposed to dynamic changes in intraocular pressure (IOP), the effects of such biomechanical stressors on outflow tissue function have not been analyzed. In particular, changes in IOP with each heartbeat have been measured in human eyes approximating 2.7 mmHg/sec. The purpose of this dissertation is to determine the effect(s) of ocular pulse on conventional outflow tissue regulation and the effect that contractility plays in this mechanical stress-mediated response. The central hypothesis directing this research is that cyclic intraocular pulsations (i.e. ocular pulse) play a significant role in conventional outflow facility.In order to address our hypothesis we studied the effect of biomechanical stressors on conventional outflow physiology using three different strategies: (1) by comparing conventional outflow endothelial cells to blood and lymphatic capillary endothelia, we gained a better understanding of the effects of biomechanical stress on conventional outflow tissue physiology, (2) by modifying the anterior segment perfusion model, we were able to measure the effect of ocular pulse on conventional outflow facility, and (3) by exposing trabecular meshwork cell monolayers to cyclic biomechanical pressure oscillations in the presence of compounds known to affect trabecular meshwork contractility, we were able to analyze the effect of rho-kinase-mediated contractility on the ocular pulse-associated response.Perfused human and porcine anterior segments showed a significant ocular pulse-mediated decrease in outflow facility; in addition, perfused trabecular meshwork monolayers showed an increase in intra-chamber pressure when exposed to cyclic pressure oscillations. This effect was blocked by Y27632 inhibition of rho-kinase-mediated contraction.In conclusion, the work shown in this dissertation demonstrates for the first time that trabecular outflow tissues are capable of responding to a physiologically-relevant cyclic biomechanical stress. This response can be observed as an increase in outflow resistance that translates to lower baselines in outflow facility of anterior segments and lower hydraulic conductivity of trabecular meshwork monolayers. In addition, we concluded that the observed ocular pulse-mediated response of trabecular meshwork cells is regulated by rho-kinase-induced contractility.

Extended periods of mechanical unloading are known to be detrimental to bone health. Astronauts who spend months in microgravity aboard the International Space Station (ISS) are at particular risk. It is anticipated that NASA will not drastically increase the size of the astronaut corps, and this will mean increased likelihood of repeat missions for more astronauts. Thus, it is important to better understand the effects that prolonged, multiple bouts of unloading have on bone. This study utilized the hindlimb unloaded (HU) rat model to examine bone loss and recovery for single and double unloading bouts. Adult male Sprague-Dawley rats (6 months old) were randomized into the following groups: baseline (sacrificed at 6 months), 1HU7 (unloaded for 1 month, weight-bearing recovery for 3 months), 2HU10 (unloaded for 1 month, recovered for 2 months, unloaded for another month, and then recovered 2 months), 1HU10 (normal cage activity until 1 month HU ending at month 10, 2 month recovery followed), and aging controls (remained ambulatory throughout experiment). Every month (28 days), animals were terminated and the left femurs were excised, resulting in n=15 per group for each time point. Mineral and geometric properties were measured using peripheral quantitative computed tomography (pQCT) at the distal femur metaphysis, and quasi-static reduced platen compression (RPC) was used to estimate the mechanical properties of cancellous bone. Strength indices based on pQCT parameters were calculated as predictors of mechanical properties. Bone mass properties decreased due to HU and recovered within 2-3 months post-HU. A combination of increased periosteal apposition and endocortical resorption also occurred during HU. The initial HU bout suppressed normal age-related increases in mechanical properties and recovered within 1-2 months. Cancellous compressive strength index (CSI) most closely matched changes in mechanical properties. A second HU bout after two months recovery had a less detrimental effect on pQCT parameters but a greater negative impact on mechanical properties, when compared to pre-HU values. The opposite is true for mechanical properties if loss is characterized relative to aging controls. Recovery after the second HU period did not appear to be significantly affected by a previous bout of HU.

Objective: Injuries to the marrow cavity result in rapid bone formation followed by regeneration of the marrow. It is not known whether this process is affected by age, although the quality of marrow is markedly different in young and old animals. To test if marrow restoration differs with age, we used the rat tibial bone marrow ablation model, which has been used to examine calcification, osteointegration of metal implants, and remodeling of bone graft substitutes. Methods: Marrow was ablated in the left tibia of seven rats (rNu/rNu) per time point. At 0,7,14,21,28,35 and 42 days post-surgery, treated tibias and contralateral tibias were harvested and fixed in buffered formalin. Both tibias were scanned using microCT and trabecular and cortical BVF/TV calculated. Mid-sagittal sections of decalcified bones were stained with H&E and BVF/TV calculated. Results: MicroCT analysis of 1-month animals showed increased bone formation on day-7 and on day-21 the marrow was restored. Increased bone was seen in 3-month animals on day-7 and day-14, but it was significantly less than in 1-month rats. By day-21, trabecular bone was reduced by 50%. 10-month animals had less trabecular bone at day-7 and 14, but bone remained in the medullary canal through day-1. Histomorphometry indicated that bone formation peaked at day-7 in 1-month rats with remodeling underway by day-14. Bone formation in 3-month rats also peaked at day-7, but restoration occurred by day-21. However, in 10-month rats, peak bone occurred on day-14, with remodeling on day-28. Conclusions: Aged animals produced less primary bone than younger animals and remodeling was initiated later. Differences in micro-CT and histomorphometric analyses may reflect a reduction in calcification of the osteoid in the 10-month old animals. (Supported by Boston Scientific, Inc.)

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. Elevated intraocular pressure (IOP), resulting from increased aqueous humor outflow resistance, is a major risk factor for the development and progression of POAG. Outflow resistance in the trabecular outflow pathway is mainly (50-75%) generated in the juxtacanalicular connective tissue (JCT), and partially (25-50%) in the portion distal to the inner wall of Schlemm’s canal. The details of how aqueous humor flows through these tissues and how resistance in these tissues is regulated are not fully understood in normal and POAG eyes. Aqueous humor outflow was shown to be “segmental”, with discontinuous active regions of aqueous humor filtration along the trabecular outflow pathway that can be labeled with perfused fluorescent tracers and measured as effective filtration area (EFA). In this study, we investigated the relationship between changes in EFA along the trabecular outflow pathway and outflow facility/IOP under two experimental conditions. The first experiment was designed to increase outflow facility by using netarsudil, a recently approved Rho kinase inhibitor class glaucoma medication, in normal human donor eyes. The second experiment was designed to increase IOP with topical steroid treatment for 5 weeks in mice. The purpose of this study is to verify whether EFA can be modulated by netarsudil or steroid treatment and to demonstrate the morphological changes that may be responsible for the changes of EFA. We analyzed EFA along the trabecular outflow pathway and found that elevated/reduced EFA correlated with increased outflow facility/IOP. Guided by EFA, we performed detailed morphological comparison between the active and inactive portions of aqueous humor filtration tissue to evaluate possible structural changes involved in EFA regulation. We found that increased EFA was associated with a loosened JCT structure and dilated episclearal veins, while decreased EFA was associated with a compacted JCT structure, increased deposition of curly collagen and/or fibrillary structure in the trabecular meshwork, and increased basement membrane continuity. Our data suggest that the netarsudil/steroid-induced morphological changes in the trabecular outflow pathway can result in either an increase or decrease in EFA, which in turn contributes to the regulation of outflow facility/IOP. / 2020-10-24T00:00:00Z

La osteoporosis es una enfermedad ósea que se manifiesta con una menor densidad ósea y el deterioro de la arquitectura del hueso esponjoso. Ambos factores aumentan la fragilidad ósea y el riesgo de sufrir fracturas óseas, especialmente en mujeres, donde existe una alta prevalencia. El diagnóstico actual de la osteoporosis se basa en la cuantificación de la densidad mineral ósea (DMO) mediante la técnica de absorciometría dual de rayos X (DXA). Sin embargo, la DMO no puede considerarse de manera aislada para la evaluación del riesgo de fractura o los efectos terapéuticos. Existen otros factores, tales como la disposición microestructural de las trabéculas y sus características que es necesario tener en cuenta para determinar la calidad del hueso y evaluar de manera más directa el riesgo de fractura. Los avances técnicos de las modalidades de imagen médica, como la tomografía computarizada multidetector (MDCT), la tomografía computarizada periférica cuantitativa (HR-pQCT) y la resonancia magnética (RM) han permitido la adquisición in vivo con resoluciones espaciales elevadas. La estructura del hueso trabecular puede observarse con un buen detalle empleando estas técnicas. En particular, el uso de los equipos de RM de 3 Teslas (T) ha permitido la adquisición con resoluciones espaciales muy altas. Además, el buen contraste entre hueso y médula que proporcionan las imágenes de RM, así como la utilización de radiaciones no ionizantes sitúan a la RM como una técnica muy adecuada para la caracterización in vivo de hueso trabecular en la enfermedad de la osteoporosis. En la presente tesis se proponen nuevos desarrollos metodológicos para la caracterización morfométrica y mecánica del hueso trabecular en tres dimensiones (3D) y se aplican a adquisiciones de RM de 3T con alta resolución espacial. El análisis morfométrico está compuesto por diferentes algoritmos diseñados para cuantificar la morfología, la complejidad, la topología y los parámetros de anisotropía del tejido trabecular. En cuanto a la caracterización mecánica, se desarrollaron nuevos métodos que permiten la simulación automatizada de la estructura del hueso trabecular en condiciones de compresión y el cálculo del módulo de elasticidad. La metodología desarrollada se ha aplicado a una población de sujetos sanos con el fin de obtener los valores de normalidad del hueso esponjoso. Los algoritmos se han aplicado también a una población de pacientes con osteoporosis con el fin de cuantificar las variaciones de los parámetros en la enfermedad y evaluar las diferencias con los resultados obtenidos en un grupo de sujetos sanos con edad similar.Los desarrollos metodológicos propuestos y las aplicaciones clínicas proporcionan resultados satisfactorios, presentando los parámetros una alta sensibilidad a variaciones de la estructura trabecular principalmente influenciadas por el sexo y el estado de enfermedad. Por otra parte, los métodos presentan elevada reproducibilidad y precisión en la cuantificación de los valores morfométricos y mecánicos. Estos resultados refuerzan el uso de los parámetros presentados como posibles biomarcadores de imagen en la enfermedad de la osteoporosis. / Alberich Bayarri, Á. (2010). In vivo morphometric and mechanical characterization of trabecular bone from high resolution magnetic resonance imaging [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/8981 / Palancia

Osteoporosis is a bone disease associated with fracture risk. Accurate assessments of fracture risk, guidelines to initiate preventive intervention, and monitoring treatment response are of paramount importance in public health. Clinically, osteoporosis is defined by low bone mineral density, which explains 65-75% of the variance in bone stiffness. The remaining variability is due to the cumulative and synergistic effects of various factors, including trabecular bone micro-architecture. Osteoporostic imaging is critically important in identifying fracture risks for planning of therapeutic intervention and monitoring response to treatments. In this work, quantitative analysis of trabecular bone micro-architecture using volumetric imaging techniques and computational biomechanical simulation through finite element modeling (FEM) are applied on in vivo imaging for various human studies. The ability of imaging methods in characterizing trabecular bone micro-architecture was experimentally examined using MRI and multi-row detector CT. They were found suitable for cross-sectional and longitudinal studies in monitoring changes of trabecular micro-architectural quality in clinical research. A framework which consists of robust segmentation of in vivo images and quality mesh generator, was constructed for FEM analysis. The framework was experimentally demonstrated effcient and effective to predict bone strength under limited spatial resolution. The ability of distinguishing bone strengths of different groups were evaluated on various human studies. And the relation between FEM and image-based micro-architectural measures was explored. Quantitative analysis supports the hypothesis that trabecular bone have distinct structural properties in different anatomic sites and the osteoporosis related change of the micro-architecture also varies. It highlight the importance of standardizing the definition of bone scan locations and the segmentation of such well-defined regions. A shape modeling method was proposed to solve the problem and its application in human proximal femur using MRI were presented. The method was compared with manual segmentation and found highly accurate. Together with tools developed for quantitative analysis, this work facilitates future researches of trabecular bone micro-architecture in different anatomic sites.

[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/10251/149376 / TESIS