The osteocytes are the most abundant and longest living bone cells, embedded in the bone matrix. They are interconnected with each other through dendrites, located in slender canals called canaliculi. The osteocyte lacunae, cavities in which the cells are located, together with the canaliculi form a communication network throughout the bone matrix, permitting transport of nutrients, waste and signals. These cells were firstly considered passive, but lately it has become increasingly clear their role as mechanosensory cells and orchestrators of bone remodeling. Despite recent advances in imaging techniques, none of the available methods can provide an adequate 3D assessment of the lacuno-canalicular network (LCN). The aims of this thesis were to achieve 3D imaging of the LCN with synchrotron radiation X-ray computed tomography (SR-CT) and to develop tools for 3D detection and segmentation of this cell network, leading towards automatic quantification of this structure. We demonstrate the feasibility of parallel beam SR-CT to image in 3D the LCN (voxel~300 nm). This technique can provide data on both the morphology of the cell network and the composition of the bone matrix. Compared to the other 3D imaging methods, this enables imaging of tissue covering a number of cell lacunae three orders of magnitude greater, in a simpler and faster way. This makes possible the study of sets of specimens in order to reach biomedical conclusions. Furthermore, we propose the use of divergent holotomography, to image the ultrastructure of bone tissue (voxel~60 nm). The image reconstruction provides phase maps, obtained after the application of a suitable phase retrieval algorithm. This technique permits assessment of the cell network with higher accuracy and it enables the 3D organization of collagen fibres organization in the bone matrix, to be visualized for the first time. In order to obtain quantitative parameters on the geometry of the cell network, this has to be segmented. Due to the limitations in spatial resolution, canaliculi appear as 3D tube-like structures measuring only 1-3 voxels in diameter. This, combined with the noise, the low contrast and the large size of each image (8 GB), makes the segmentation a difficult task. We propose an image enhancement method, based on a 3D line filter combined with bilateral filtering. This enables improvement in canaliculi detection, reduction of the background noise and cell lacunae preservation. For the image segmentation we developed a method based on variational region growing. We propose two expressions for energy functionals to minimize in order to detect the desired structure, based on the 3D line filter map and the original image. Preliminary quantitative results on human femoral samples are obtained based on connected components analysis and a few observations related to the bone cell network and its relation with the bone matrix are presented.

Hip fracture is a global and a growing public health problem. More women than men sustain hip fractures, the incidence increases exponentially with age and mean age is above 80. About one third of hip-fracture patients suffer from dementia and are prone to develop acute confusional state (delirium). Delirium is one of the most common complications after hip-fracture surgery, and seriously impacts on morbidity and mortality. Malnutrition is also common in hip-fracture patients and is associated with postoperative complications, such as delayed healing of the wound, infections and decubitus ulcers. Arthroplasty is usually preferred procedure in displaced femoral neck fractures but is, however, controversial in patients with dementia due to the fear of dislocation of the prosthesis. The aims of this thesis are to identify risk factors for delirium and the impact of delirium on rehabilitation outcome, to evaluate whether a postoperative multi-factorial intervention program could reduce delirium, to investigate the effect of a nutritional intervention and to evaluate complications, functional outcome and mortality regarding two surgical methods, hemiarthroplasty (HAP) and internal fixation (IF), in old patients with femoral neck fracture. Thirty-eight out of 61 consecutive patients (62%) were delirious on admission to hospital or developed postoperative delirium. An increased risk of postoperative delirium was found among hip-fracture patients with dementia and/or depression. Delirious patients were hospitalized longer, were more dependent in their activities of daily living, had poorer psychological well-being and suffered more complications than non-delirious patients. A postoperative multi-factorial and multidisciplinary intervention program reduced the incidence, at 55% vs 75% (p=0.003), and number of days with delirium, 5 vs 10 days (p=0.009). Postoperative complications were also reduced; decubitus ulcers 9% vs 22% (p= 0.010), urinary tract infections 31% vs 51% (p=0.005), falls 12% vs 27% (p=0.007), and the mean hospitalization period was 10 days shorter in the intervention group (p=0.030). Malnutrition was common among all these patients (53 %) and associated with postoperative complications such as decubitus ulcers and delirium. However, the nutritional intervention had no effect on nutritional parameters at four months, nevertheless men had better nutritional outcomes than women. A higher proportion of patients with dementia operated on using HAP had regained their pre-fracture ability to walk independently at the one-year follow up compared with those operated on using IF. Six of 83 patients dislocated their HAP during hospitalization and during an episode of delirium, none had dementia. No difference in mortality between the surgical methods was seen. Dementia per se should not be a reason to disqualify patients from being treated with the most appropriate surgical method. It is clinically important to discriminate between dementia and delirium, since delirium can be prevented and treated even in patients with dementia. Old patients undergoing surgery have special needs that are not always catered for in ordinary orthopaedic or surgical wards. The special care for these patients should include: a combined nursing and medical care based on comprehensive geriatric assessments, systematic prevention, detection and treatment of postoperative complications such as delirium, hypoxemia, urinary tract infections, pain, malnutrition and an active rehabilitation. It is obvious that improved quality of care reduces patient suffering and seemingly the costs for society.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser.

Dans le cadre de ce travail de thèse nous nous sommes intéressés à deux pathologies fémoro-acétabulaires dont la pathogénie semble liée aux « conditions biomécaniques » locales. La première partie de cette thèse était consacrée à l’analyse de l’influence de l’anatomie osseuse sur l’apparition de l’ostéonécrose aseptique de la tête fémorale. Nous avons réalisé des analyses analytique de l’anatomie des patients souffrant d’ONA (notre hypothèse était que nous retrouverions un profil anatomique particulier chez les patients souffrant d’ONA par rapport à la population générale.Nos résultats démontrent que les patients souffrant d’ONA présentent fréquemment une anatomie particulière. Notre modèle en éléments finis de la hanche de dix patients souffrant d’ONAi, a permis de valider notre hypothèse puisqu’il existe un recouvrement quasi-parfait, entre la zone de nécrose osseuse et celle supportant les contraintes fémoro-acétabulaires. L’hypothèse selon laquelle une pathogénie mécanique puisse être responsable du développement l’ostéonécrose aseptique de la tête fémorale est vérifiée par nos travaux.Dans la seconde partie de cette thèse nous avons décrit le rôle mécanique du LA par une évaluation multimodale combinant analyse cinématique,de contraintes fémoro-labrales et enfin analyse en éléments finis. Les résultats de ces études ont permis de constater que le LA se déforme lors du mouvement reflétant une transmission de contraintes fémoro-labrales lors du mouvement d’abduction. Ces contraintes ont pu être enregistrées à l’aide de capteurs piezo-resistifs, elles augmentent lors du mouvement d’abduction. Ces éléments ont été confirmés par notre modèle en éléments finis. / As parts of this thesis we focused on two femoro-acetabular diseases whose pathogenesis appears to be related to "biomechanical local conditions". The first part of this thesis was devoted to analyze the influence of bony anatomy on the development of aseptic osteonecrosis of the femoral head. We thus aimed to analyze ONA patients’ anatomy in a matched-controlled fashioned study. Our results demonstrate that patients with ONA often present a particular anatomy. A finite element model of ten iONA hips validated our hypothesis since we found an overlap between bone necrosis area and femoro-acetabular strains bearing area. The assumption that a mechanical pathogenesis may be responsible for ONA development has been confirmed by our results.If the relationship between bony anatomy and bone disease is quite intuitive, acetabular labrum involvement (AL) in the regulation of femoro-acetabular mechanical conditions is unclear. The mechanical role of the AL is widely controversial, though some authors attributed, AL, a key role in hip joint’s mechanics, others advocated its complete resection in case of painful traumatic tears. We tried to demonstrate AL’s mechanical role in a multimodal analysis combining kinematic, strains and finite element analysis. The AL deforms during abduction movement reflecting femoro-labral strains’ transmission. Those strains have been recorded using piezo-resistive sensors, they increase during adduction to abduction movement. These elements were confirmed by our finite element model: labral resection changed the Femoro-acetabular strains to the detriment of cartilage surfaces.

L’état de santé des personnes âgées se dégrade, les niveaux de dépendance s’accroissent, induisant de profondes conséquences sur l’organisation sanitaire en France. Les fractures du col du fémur illustrent ce défi au regard de leur fort impact sur la qualité de vie et sur la morbi-mortalité des patients. Notre étude quantitative et qualitative, (Jan. 2012 - Jan. 2013) au sein du principal service de chirurgie orthopédique d’Alsace, a permis de retracer le parcours de soin de 107 patients âgés de 75 ans et plus. Notre principale conclusion est que le patient n’a que très peu de place dans le processus décisionnel de son parcours de soin. Cela est d’autant plus dommageable que cette fracture revêt une double signification: physique (besoin d’assistance accrue) et symbolique (dépendance anticipée). Notre étude interactionniste permet de dégager des pistes d’actions opérationnelles dans les domaines sanitaires, politiques et éthiques afin de limiter les effets délétères de cette pathologie. / In a context of depressed health-conditions for elderly people, the levels of dependency are rising. It induces deep consequences for the entire health care organisation. For instance, the fractures of the femoral neck (FFN) represent a healthcare challenge regarding their strong impact on patients’ quality of life and on their morbity-mortality. We conducted a qualitative and quantitative study (Jan. 2012- Jan. 2013) within the main department of orthopedic surgery in Alsace in order to track the healthcare paths of 107 patients of 75 years-old or more. Our main conclusion is that patients are poorly involved in the decisions for their care. This is all the more harmful because the FFN is in fact dual. It is both a physical (higher assistance needed) and a symbolic (earlier dependency) breakage. Our interactionist study identifies areas for pragmatic actions in health-care, public policies and ethic that could contribute to absorb / reduce the pernicious effects of this pathology.

La physiopathologie et l'évolution structurale de l'ostéonécrose de tête fémorale (ONTF) sont des processus encore largement méconnus. Les objectifs de cette thèse ont été de rechercher des modifications de composition et de structure de l'os trabéculaire et de l'os sous-chondral dans l'ONTF. Un travail préliminaire s'est intéressé aux modifications de composition osseuse en spectrométrie Raman induites par l'embaumement afin de déterminer les témoins les plus appropriés pour comparer les os pathologiques. Des tissus osseux fémoraux issus de 5 sujets anatomiques embaumés ont ainsi été comparés à ceux de 5 sujets anatomiques frais. Le premier travail sur l'ONTF a consisté à rechercher des modifications des paramètres physico-chimiques minéraux et organiques en spectrométrie Raman de l'os trabéculaire de tête fémorale chez 11 patients ayant une ONTF versus 11 sujets frais. Le second travail concernant l'ONTF a porté sur l'étude de l'os sous-chondral. Cette recherche a prévu l'inclusion de 15 patients ayant une ONTF à 15 patients ayant une coxarthrose nécessitant un remplacement prothétique. Une évaluation IRM avec séquences usuelles, séquences de perfusion et séquences DIXON était réalisée préalablement à la chirurgie. Après la chirurgie, l'ensemble de la tête fémorale était ensuite analysé en nano-scanner (nano-CT), puis des biopsies en zones d'intérêt ont été réalisées et analysées par histologie, nano-CT avec amplificateur de contraste et spectrométrie Raman.RésultatsLa composition des tissus osseux fémoraux des sujets anatomiques frais et embaumés différaient de manière significative sur les paramètres minéraux et organiques. La composition de l'os trabéculaire sur les zones d’intérêt ne différait pas entre les patients ayant une ONTF et le groupe de sujets anatomiques frais après ajustement sur l'âge. Le volume de nécrose définie en IRM par la zone en hyposignal T1 est corrélé au volume de nécrose incluant la zone sclérotique en nano-CT. Concernant l'os sous-chondral, les résultats préliminaires mettent en évidence des différences de composition minérale et organique en spectrométrie Raman au niveau de la plaque souschondrale entre les zones d’intérêt du groupe ONTF et avec le groupe coxarthrose. Les résultats préliminaires qualitatifs des biopsies en nano-CT et en histologie suggèrent que l'atteinte de la plaque sous-chondrale est prédominante sur celle de l'os trabéculaire souschondral. L’évaluation IRM (séquence DIXON) et en nano-CT de la richesse adipeuse suggère une relative pauvreté adipeuse de la tête fémorale mais une richesse excessive du col fémoral.Ce travail apporte des éléments supplémentaires suggérant que la désorganisation de l'os trabéculaire au cours de l'ONTF est une conséquence d'une atteinte massive de l'os sous-chondral. / IntroductionThe pathophysiology and structural evolution of the osteonecrosis of the femoral head (ONFH) are poorly understood. The objectives of this thesis were to search for modifications of composition and structure of both the trabecular and the subchondral bone occurring during ONFH.MethodsA preliminary study looked into the potential modifications of bone composition induced by embalmment procedures using Raman spectroscopy in order to determine which controls are the most appropriate for comparisons with pathological bones. Femoral bones from 5 embalmed anatomical subjects were compared to femoral bones from 5 subjects that did not undergo any preservation procedure. The first work on ONFH addressed the potential modifications of trabecular bone mineral and organic physico-chemical parameters using Raman spectroscopy. The study included bone samples from femoral heads of 11 patients affected with ONFH and compared them to samples from 11 fresh anatomical subjects. The second study on ONFH addressed modifications of the subchondral bone. The study included 15 patients suffering from ONFH and 15 patients affected with hip osteoarthritis (OA) requiring joint prosthetic replacement. MRI examination that included standard medical sequences as well as experimental perfusion and DIXON sequences was performed prior to surgery. Once removed, the femoral heads were scanned using a nano-CT and samples of regions of interest were performed and analysed using histology, nano-CT with contrastenhancer marking and Raman spectroscopy.ResultsBone femoral mineral and organic composition was significantly altered in embalmed samples. Trabecular bone composition did not differ in any of the regions of interest inside the group of patients with ONFH nor in comparison with the control group of embalmed subjects after adjustment on age. The volume of the necrotic zone defined by the hypo-T1 MRI signal correlates to the volume including the sclerotic zone measured by nano-CT. Regarding the subchondral bone, preliminary results found differences of mineral and organic composition of the subchondral plate between zones of the ONFH group and with the OA group. Qualitative preliminary results from the study of biopsies analysed with the nano-CT and histology suggest that there are alterations of the subchondral plate and of the subchondral trabecular bone to a lesser extent. MRI examination with the DIXON sequence and nano-CT scans suggest that there is a decrease of the adipose content in the femoral head but an increase in the femoral neck in the ONFH group compared to the OA group.ConclusionThis work adds further evidence advocating that trabecular disorganization during ONFH is a consequence of massive alterations of the subchondral bone.

Made available in DSpace on 2016-06-02T20:18:09Z (GMT). No. of bitstreams: 1 TeseFVS.pdf: 3401633 bytes, checksum: b22a99a2e3db18dc60852a024a747b7f (MD5) Previous issue date: 2004-02-05 / Universidade Federal de Minas Gerais / studies about muscle regeneration and injury used invasive methods in animals. Although the muscle regeneration process in many mammals is similar to the one found in humans, it is necessary to improve the application of non-invasive procedures used in the evaluation of the muscle regeneration and injury in humans. Non-invasive techniques such as surface electromyography, isokinetic dynamometry and nuclear magnetic resonance (NMR) for imaging have been used in studies in humans for the evaluation of the skeletal muscle. However, studies in which all these procedures are used together, allowing a more detailed evaluation of the muscle morphology and function, are rare.Thus, the aim of this study was to evaluate the behaviour of the medium maximal isometric torque, the electrical activity and the muscle pain before the injury, during the 7 days after the injury and also between the 21st and 30th days after the injury, when the muscle has already regenerated. For this, a injury was induced in the quadriceps femoris muscle through intense eccentric exercise. To confirm if the model utilized was effective to produce the muscle injury, the plasma activity of the creatine kinase (CK) was also evaluated and the NMR for imaging of the quadriceps femoris muscle was realized. Ten university student volunteers (21,9±1,5), sedentary and without musculoskeletal dysfunction in the lower right limb participated in this study. The extensor medium maximal isometric torque was evaluated through maximal isometric contraction with the knee joint at 90º of flexion, in the isokinetic dynamometer (Biodex Multi-joint System 2 da BIODEX MEDICAL SYSTEM Inc). The electrical activity (Root Mean Square-RMS and Median Frequency) of the vastus medialis oblique (VMO), vastus lateralis (VL) and rectus femoris (RF) muscles was analysed simultaneously to mensuration of the isometric torque, utilizing a Digital Analogue Conversor A/D (LYNX) and single differential active electrodes of surface (LYNX). The quantitative and qualitative analysis of the pain were realized by Visual Analogue Scale (VAS) and by Brazilian Version of Short-Form McGill Pain Questionnaire. The activity of CK was measured utilizing the Kit CK-NAC UV unitest (Wiener lab) and the NMR was realized in the ToRM 0.5 equipment. For the induction of quadriceps femoris muscle injury, the volunteers were submitted to 4 series of 15 maximal eccentric isokinetic contractions, at angle velocity 5º.s-1. The results of this study demonstrated that the medium maximal isometric torque reduced significantly until the 4th day after the eccentric exercise (immediately after and 1st - 4th days after, p<0.01; 4th day after, p<0.05). The RMS of the VMO, VL and RF muscles reduced significantly the 2nd day after (p<0.01, p<0.01 e p<0.05, respectively). However, the RMS of the VL and RF muscles between the 21st and 30th days was significantly greater than before the exercise (p<0.01). There wasn t alteration in the median frequency after tthe eccentric exercise (VMO, p= 0.90; VL, p= 0.55 e RF, p= 0.89). The intensity of pain was greater until the 3rd day, and the peak occurred in the 2nd day after (p<0.01). The McGill Pain Questionnaire demonstrated that the word heavy was the most used to describe the pain after the induced injury by eccentric exercise. The peak of activity of the CK occurred in the 2nd day after the eccentric exercise(p<0.05). The evaluation by NMR demonstrated that the greatest extension of injury occurred in the 2nd and 7th days after, and some voluteers still showed injury sign between the 21st and 30th days. In conclusion, the eccentric exercise reduced the medium maximal isometric torque, increased the activity of the CK, changed the RMS and resulted in pain, which were gradually recovered in one week, despite the presence of muscle injury. / A maioria dos estudos sobre a lesão e regeneração muscular utilizou métodos invasivos em animais. Embora o processo de regeneração muscular em muitos mamíferos seja similar ao encontrado em humanos, é necessário melhorar a aplicação de procedimentos não-invasivos usados na avaliação da lesão e regeneração muscular em humanos. Técnicas não-invasivas tais como a eletromiografia de superfície, a dinamometria isocinética e a ressonância magnética nuclear (RMN) por imagem têm sido utilizadas em estudos em humanos para a avaliação do músculo-esquelético. No entanto, raros são os estudos em que todos esses procedimentos são utilizados conjuntamente, permitindo uma avaliação mais detalhada da função e da morfologia muscular. Assim, o objetivo desse estudo foi avaliar o comportamento do torque isométrico máximo médio, a atividade elétrica e a dor muscular antes da lesão, durante os 7 primeiros dias pós-lesão e também entre o 21º e 30º dias pós-lesão, quando o músculo já se regenerou. Para isso, foi induzida lesão no músculo quadríceps femoral através de exercício excêntrico intenso. Para comprovar se o modelo utilizado foi efetivo para produzir a lesão muscular, foi também avaliada a atividade plasmática da creatina-quinase (CK) e foi realizada a RMN por imagem do músculo quadríceps femoral. Participaram deste estudo 10 universitárias voluntárias (21,9±1,5), sedentárias e sem qualquer patologia osteomioarticular no membro inferior direito. O torque isométrico máximo médio extensor foi avaliado através de contrações isométricas máximas com a articulação do joelho à 90º de flexão, num Dinamômetro Isocinético (Biodex Multi-joint System 2). A atividade elétrica (Root Mean Square-RMS - Raiz Quadrada da Média dos Quadrados e a Freqüência Mediana) dos músculos vasto medial oblíquo (VMO), vasto lateral (VL) e reto femoral (RF) foi analisada simultaneamente à mensuração do torque isométrico, utilizando-se um Conversor Analógico Digital A/D (LYNX) e eletrodos ativos diferenciais simples de superfície (LYNX). As análises quantitativas e qualitativas da dor foram realizadas pela Escala Visual Analógica Visual Analog Scales (VAS) e pela Versão Brasileira Resumida do Questionário McGill de Dor. A atividade da CK foi mensurada utilizando-se o Kit CK-NAC UV unitest e a RMN foi realizada no equipamento ToRM 0.5. Para a indução da lesão no músculo quadríceps femoral, as voluntárias foram submetidas a 4 séries de 15 contrações isocinéticas excêntricas máximas, à velocidade angular de movimento de 5º/s. Os resultados deste estudo demonstraram que o torque isométrico máximo médio diminuiu significativamente até o 4º dia após o exercício excêntrico (imediatamente após e do 1º ao 3º dias após, p<0,01; 4º dia após, p<0,05) . O RMS dos músculos VMO, VL e RF diminuiu no 2º dia após o exercício (p<0,01, p<0,01 e p<0,05, respectivamente). Entretanto, o RMS dos músculos VL e RF entre o 21º e 30 º dias foi maior ao antes do exercício (p<0,01). Não houve alteração na freqüência mediana após o exercício excêntrico (VMO, p= 0,90; VL, p= 0,55 e RF, p= 0,89). A intensidade da dor foi maior até o 3º dia após o exercício excêntrico, com o pico ocorrendo no 2º dia após (p<0,01). O questionário McGill demonstrou que a palavra pesada foi a mais utilizada para caracterizar a dor após a lesão induzida pelo exercício excêntrico. O pico da atividade da CK ocorreu no 2º dia após o exercício excêntrico (p<0,05). A avaliação pela RMN demonstrou que a maior extensão da lesão ocorreu no 2º e 7º dias após, com algumas voluntárias ainda apresentando sinais de lesão entre o 21º e 30º dias. Em conclusão, o exercício excêntrico diminuiu o torque isométrico máximo médio, aumentou a atividade da CK, alterou o RMS e resultou em dor, os quais se recuperaram gradualmente na primeira semana, apesar da presença de lesão muscular.