<p>The risk of fracture is higher in adults with type 2 diabetes compared to controls without type 2 diabetes, despite normal or higher than normal bone mineral density (BMD). In addition to BMD, bone strength depends on other factors such as structural and material <em>bone qualities</em>, which are not accounted for in BMD measurements. The objective was to determine whether structural and material <em>bone qualities</em> are different in adults with type 2 diabetes compared to controls without type 2 diabetes. First, a cross-sectional study was undertaken using MRI to investigate distal radius trabecular bone microarchitecture, a structural <em>bone quality.</em> In women with type 2 diabetes, trabecular bone holes were larger compared to controls, which is important because greater trabecular bone hole size is related to reduced bone strength. Next, a two year prospective study was conducted with the participants involved in the cross-sectional study to determine whether changes in trabecular bone microarchitecture are different in women with type 2 diabetes compared to controls. There was a greater increase in the number of trabecular bone holes in women with type 2 diabetes compared to controls, which provides early evidence of trabecularization of cortical bone in women with type 2 diabetes. In the third study, quantitative backscattered electron imaging (qBEI) was used to derive bone mineralization density distribution (BMDD) outcomes for bone samples from adults with and without type 2 diabetes to compare material <em>bone quality. </em>There was evidence of elevated bone calcium concentration and reduced mineralization heterogeneity in bone samples from adults with type 2 diabetes compared to controls, which may contribute to bone brittleness. In summary, differences in structural and material <em>bone qualities </em>identified in this body of work provide explanations for elevated fracture risk in adults with type 2 diabetes.</p> / Doctor of Science (PhD)

This work deals with issue of human wrist and appropriate total wrist implant allowing a restoration of hand mobility approaching physiological condition after traumatic and degenerative diseases. Treating these diseases are very complex. These issues including a biological and medical issues. To determine the appropriate treatment method and select right total wrist implant is important to know the behavior the human wrist at all stages in terms of medical and biomechanical. For this reason, it was developed a biomechanical study including computation model of human wrist allowing solution of strain and stress of hand in physiological and pathological conditions and condition after total wrist implant. The frost remodeling of bone tissue was used for analysis of human wrist bone tissues and bone tissues after application of total wrist implant RE-MOTION™ Total Wrist.

Le système ostéocytaire soulève un intérêt croissant depuis quelques années car il est joue un rôle important dans l'adaptation de l'os. Le système ostéocytaire est inclus dans un réseau poreux dénommé le réseau lacuno-canaliculaire (LCN). L’observation du système ostéocytaire est difficile car les ostéocytes sont profondément enfouies dans la matrice osseuse et difficilement accessible par les techniques optiques. Récemment l’équipe de Creatis a montré la faisabilité d’imager le LCN en 3D grâce à la micro tomographie par rayonnement synchrotron. Toutefois, il n’existe actuellement pas de méthodes d’analyse permettant de quantifier, de façon automatique, le réseau lacuno-canaliculaire en 3D. L’objectif de cette thèse était de développer des méthodes d’analyse d’images permettant d’extraire des paramètres quantitatifs sur le réseau lacuno-canaliculaire. La première partie, consacrée à l’état de l’art. Le chapitre 1 présente les objectifs de ce travail. Le chapitre 2 rappelle les éléments de base sur le tissu osseux et présente les caractéristiques du réseau lacuno-canaliculaire. Le chapitre 3 présente les différentes méthodes d’imagerie utilisées jusqu’à présent pour étudier le réseau lacuno-canaliculaire. Le chapitre 4 présente l’état de l’art sur les paramètres qui sont classiquement utilisés pour caractériser le réseau lacuno-canaliculaire. La seconde partie est consacrée aux contributions de ce travail. Le chapitre 5 présente les deux systèmes expérimentaux de l’ESRF sur lesquels des images d’échantillons osseux ont été acquises. Le chapitre 6 décrit la méthode développée pour la quantification des lacunes ostéocytaires à partir d’images à l’échelle micrométrique. Elle propose de calculer des paramètres issus des moments géométriques ainsi que des paramètres basés sur la notion de volumes intrinsèques. Les méthodes sont appliquées à une série de 13 échantillons acquis en collaboration avec le Laboratoire d’Imagerie Paramétrique, Paris. Les résultats obtenus sont comparés et discutés par rapport à ceux de la littérature. Le chapitre 7 décrit la quantification des canalicules reliant les ostéocytes à partir d’images à l’échelle sous-micrométrique. En particulier, nous nous sommes intéressées à estimer le nombre de canalicules issues d’une lacune ostéocytaire, paramètre encore jamais mesuré en 3D. L’évolution de ce paramètre en fonction de la distance au centre de la lacune a permis de mettre en évidence et de quantifier la ramification des canalicules. Le chapitre 8 propose l’application des méthodes développées à une série d’échantillons acquis en collaboration le groupe de Sharmila Majumdar à l’université de San Francisco. Dans ce chapitre, nous avons travaillé sur une nouvelle méthode de segmentation du réseau lacuno-canaliculaire basée sur une méthode de chemins géodésiques. Les premiers résultats acquis sur 8 échantillons humains d’âges différents sont présentés. Finalement, le chapitre 9 conclut ce travail et présente des perspectives. / The osteocyte system has raised increasing interest in the recent years, since it is hypothesized to play an important role in orchestrating bone adaptation through mechanosensation and bone mechanotransduction mechanism. The osteocytes are deeply buried within the bone matrix, where their bodies are encysted in cavities called lacunae and their stellular processes are enclosed in tunnels called canaliculi. Together, they formed the lacuno-canalicular network (LCN). The geometry of the LCN is of importance since it is supposed to potentially affect and reflect the viability of the osteocyte and is supposed to be related to biomechanical constraints at the cell level. However, studying the LCN is quite challenging, due to limitations in an ideal imaging modality and the lack of quantitative analysis tools. In this thesis, we propose computational efficient and automated methods to quantify the 3D morphological properties of the LCN from synchrotron radiation (SR) micro / nano-CT images. For image acquisition, we used the SR micro/nano-CT setups installed on beamlines ID19 and ID22 at ESRF. A series of human cortical samples were imaged with spatial resolutions ranging between 3.5 µm to 60 nm. For the 3D assessment of lacunae, we used an image moment-based approach to calculate the volume, length, width, height and anisotropy of each osteocyte lacuna. We employed a fast algorithm to further calculate the surface area, the Euler number and the SMI of each lacuna. Validation of segmentation and experimental results on 13 bone samples are presented. For the 3D assessment of canaliculi, we propose a method to quantify the canalicular ramification around each lacuna. After segmentation, our method first labels each lacuna from the LCN. Then, a signature of the numbers of canaliculi at different distances from the lacunar surface is estimated through the calculation of topological parameters. Validation of this method and statistical results a large 3D SR micro-CT image of a human femoral bone sample are reported. We also improved the segmentation of the canaliculi and illustrated the feasibility of the application on a series of bone samples. We investigated a segmentation approach based on minimum cost paths and geodesic voting. A parallel computation scheme was implemented to reduce the computation times. The LCN was characterized by using the previous methods. Besides, we introduced the parameters from the Voronoi tessellation. Statistical results are reported on 8 large 3D micro-CT images, including around a hundred lacunae and the canaliculi. Future works will concern the improvement of canaliculi segmentation of from images at 300 nm as well as its evaluation and further characterization of LCN from SR CT images at both 300 nm and 50 nm. This work opens many perspectives for a better knowledge of the physiopathology of bone at the cellular scale.

This work deals with issue of human wrist and appropriate total wrist implant allowing a restoration of hand mobility approaching physiological condition after traumatic and degenerative diseases. Treating these diseases are very complex. These issues including a biological and medical issues. To determine the appropriate treatment method and select right total wrist implant is important to know the behavior the human wrist at all stages in terms of medical and biomechanical. For this reason, it was developed a biomechanical study including computation model of human wrist allowing solution of strain and stress of hand in physiological and pathological conditions and condition after total wrist implant. The frost remodeling of bone tissue was used for analysis of human wrist bone tissues and bone tissues after application of total wrist implant RE-MOTION™ Total Wrist.

[ES] El acceso a una atención sanitaria de alta calidad es un marcador importante del desarrollo de las sociedades humanas. Los aportes tecnológicos a la medicina han mostrado un potencial relevante para descubrir procedimientos efectivos a nivel preventivo, diagnóstico y terapéutico. En particular, los métodos computacionales permiten el procesamiento eficaz de datos médicos y, por tanto, pueden modelar sistemas biológicos complejos. Esto ha influido en el desarrollo de la Medicina Personalizada (MP) durante las últimas décadas, donde la obtención de conocimiento específico de cada caso permite realizar intervenciones a medida, todo ello a un coste de recursos accesible. La simulación de remodelación ósea es un campo prometedor en el contexto de la MP. Predecir un proceso de adaptación ósea en un caso concreto puede dar lugar a numerosas aplicaciones en el campo de las enfermedades óseas, tanto a nivel clínico como experimental. Mediante la combinación del Método de Elementos Finitos (FEM) y los algoritmos de remodelación ósea, es posible obtener modelos numéricos de un hueso específico a partir de datos médicos (por ejemplo, una tomografía computarizada). Todo ello puede dar lugar a una revolución en la medicina personalizada. / [CA] L'accés a una atenció sanitària d'alta qualitat és un marcador important del desenvolupament de les societats humanes. Les aportacions tecnològiques a la medicina han mostrat un potencial rellevant per a descobrir procediments efectius a nivell preventiu, diagnòstic i terapèutic. En particular, els mètodes computacionals permeten el processament eficaç de dades mèdiques i, per tant, poden modelar sistemes biològics complexos. Això ha influït en el desenvolupament de la Medicina Personalitzada (MP) durant les últimes dècades, on l'obtenció de coneixement específic de cada cas permet realitzar intervencions a mesura, tot això a un cost de recursos accessible. La simulació de remodelació òssia és un camp prometedor en el context de la MP. Predir un procés d'adaptació òssia en un cas concret pot donar lloc a nombroses aplicacions en el camp de les malalties òssies, tant a nivell clínic com experimental. Mitjançant la combinació del Mètode d'Elements Finits (*FEM) i els algorismes de remodelació òssia, és possible obtindre models numèrics d'un os específic a partir de dades mèdiques (per exemple, una tomografia computada). Tot això pot donar lloc a una revolució en la medicina personalitzada. / [EN] Access to high-quality healthcare is an important marker of the development of human societies. Technological contributions to medicine have shown relevant potential to discover effective procedures at a preventive, diagnostic and therapeutic level. In particular, computational methods enable efficient processing of medical data and can therefore model complex biological systems. This has influenced the development of Personalized Medicine (PM) over recent decades, where obtaining specific knowledge of each case allows for tailored interventions, all at an affordable resource cost. Simulation of bone remodeling is a promising field in the context of PM. Predicting a bone adaptation process in a specific case can lead to numerous applications in the field of bone diseases, both clinically and experimentally. By combining the Finite Element Method (FEM) and bone remodeling algorithms, it is possible to obtain numerical models of a specific bone from medical data (for example, a CT scan). All of this can lead to a revolution in personalized medicine. / Thanks to the Valencian funding programme FDGENT/2018, for providing economic resources to develop this long-term work. / Gutiérrez Gil, J. (2023). Personalization of Bone Remodelling Simulation Models for Clinical Applications [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/202059