L’os est un matériau dont les propriétés évoluent tout au long de la vie en fonction des contraintes environnementales. Aujourd’hui, les modalités d’imagerie permettent aux cliniciens d’évaluer la qualité osseuse chez l’adulte. Malheureusement, ces outils diagnostics ne sont pas adaptés pour l’enfant (nocivité des radiations, anesthésie ou sédation nécessaire), et le développement d’un outil clinique nécessite une bonne connaissance des propriétés du tissu osseux pédiatrique.Peu d’études ont analysé les propriétés du tissu osseux au cours de la croissance. Cette pénurie de données de référence s’explique par la faible quantité d’échantillons disponible pour les essais en laboratoire et par la qualité même de ces échantillons pour la plupart «prélevés» et associés à une pathologie de l’enfant.Les objectifs de ce travail de thèse s’inscrivent dans une logique de compréhension des mécanismes et des propriétés de l’os en croissance. L’intérêt majeur de ce travail est donc d’apporter de nouvelles connaissances sur l’os cortical pédiatrique. Les propriétés mécaniques et tissulaires ont été étudiées via l’utilisation de diverses techniques: la microtomographie, la microradiographie, la FTIRM, la biochimie, la compression, la caractérisation ultrasonore et la nanoindentation. Ce travail a permis de mettre en avant l’évolution de l’os cortical pédiatrique vers un état mature: la structure des fibres de collagène se hiérarchise, le tissu se minéralise. Ces changements dans la structure du tissu osseux lui permettent de se rigidifier. Ces travaux de thèse ont permis de mieux comprendre cette évolution, et vont permettre d’avoir une 1ère base de données sur la fibula infantile. / Bone is a material whose properties change throughout life depending on environmental constraints. Today, imaging modalities allow clinicians to assess bone quality in adults. Unfortunately, these diagnostic tools are not suitable for children (harmful radiation, anesthesia or sedation required). Development of a clinical tool requires a good knowledge of pediatric bone tissue properties.Few studies have analyzed the properties of bone tissue during growth. This lack of reference data is due to the small amount of samples available for laboratory testings and the quality of these samples for the most taken and associated with a child's illness.The aims of this thesis are to understand the growing bone. The major interest of this work is to provide new knowledge on pediatric cortical bone. Mechanical, structural and chemical properties have been studied by the use of various techniques: tomography, microradiography, FTIRM, biochemistry, compression, ultrasonic characterization and nanoindentation.This work allowed to highlight that pediatric cortical bone evolves into a mature state: maturation of collagen cross-links, mineralization of bone tissue. These changes in the structure of the bone allows it to stiffen. This work allows to understand this evolution and will enable to have a first database on child fibula.

L’ostéoporose est définie par une diminution de la masse osseuse et une altération de la structure osseuse. L’évaluation de l’architecture de l’os trabéculaire vertébral est un des enjeux majeurs de recherche actuels visant à la caractérisation des modifications du tissu osseux liées au vieillissement. Par ailleurs, le traitement de la fracture vertébrale ostéoporotique par vertébroplastie a démontré son efficacité. Le ciment actuel utilisé pour la vertébroplastie est le polyméthylméthacrylate. Ce ciment est efficace pour stabiliser la vertèbre et diminuer la douleur mais il existe une toxicité pour les tissus mous avoisinant, notamment la moelle en cas de fuite, et des inquiétudes quant au risque de fracture des vertèbres adjacentes. De nouveaux ciments biointégrables du type ciments phosphocalciques supplémentés en bisphosphonates pourraient avoir leur place à l’avenir dans le traitement des vertèbres.Notre travail de thèse s’est inscrit dans un projet pluridisciplinaire de recherche sur les altérations de la structure de l’os trabéculaire vertébral, reposant sur une analyse en imagerie médicale et une étude biomécanique, et sur le développement d’un nouveau ciment phosphocalcique supplémenté en bisphosphonates.L’ensemble de nos résultats pourra nous permettre :-D’améliorer la prédiction du risque de fracture vertébrale ostéoporotique-D’optimiser les nouveaux ciments biointégrables / The current definition of osteoporosis is a low bone mass associated with a microarchitecture deterioration. Vertebral trabecular bone microarchitecture assessment is an important research topic aiming at the characterization of the modifications of the bone tissue bound to ageing. On the other hand, the vertebral fracture treatment by vertebroplasty is known to be effective. Currently the cement used in vertebroplasty is the polymethylmetacrylate (PMMA). This cement stabilizes the vertebral fracture and decreases the pain, but there are a toxicity for nearby soft tissues, in particular spinal marrow in case of leakage, and concerns as for the risk of fracture of the neighboring vertebrae. In the future, new biointegrable calcium phosphate cement supplemented in bisphosphonate could be used in the vertrebrae treatment.Our work was based on a multidisciplinary project which aimed firstly at evaluating trabecular vertebral bone microarchitecture using medical imaging and biomechanical testing in this crucial anatomical region, secondly at developing a new calcium phosphate cement supplemented in bisphosphonate. Our results may lead to:- improve the fracture risk prediction in osteoporotic vertebra- improve the new biointegrable cements

Ratas adultas foram tratadas com 2.5, 5, 10, 20 e 40x a dose fisiológica de triiodotironina (T3) por 10 semanas. Houve redução, dose-dependente, da massa óssea, volume e espessura trabecular (Tb.Th), e espessura de osso cortical. Até a dose de 10xT3, houve aumento na taxa de formação óssea (BFR). Doses maiores de T3 reduziram a BFR, e a reabsorção óssea. Esses dados mostram que, até um certo grau de tireotoxicose, a osteopenia é resultado de aumento da formação e reabsorção ósseas, com predomínio da última. Em graus mais elevados, a osteopenia é causada por redução no remodelamento ósseo, com predomínio da atividade reabsortiva. Em seguida, comparamos os efeitos do T3 e GC-1, um tireomimético seletivo pelo receptor b de T3 (TRb), no osso de camundongos fêmeas adultas. Na tíbia, o T3 reduziu a resistência, rigidez e resiliência, enquanto o GC-1 aumentou esses parâmetros e a Tb.Th, o que mostra que o GC-1 melhora a qualidade óssea. Considerando-se a seletividade do GC-1 pelo TRb, esses achados sugerem que o TRb medeia predominantemente ações positivas do T3 no osso. / Adult rats were treated with 2.5, 5, 10, 20 and 40x the physiological dose of triiodothyronine (T3) for 10 weeks. There was a dose-dependent reduction in bone mass, trabecular volume and thickness (Tb.Th), and cortical thickness. Up to 10xT3, there was an increase in the bone formation rate (BFR). Higher doses of T3 decreased BFR and bone resorption. These data show that, up to a certain degree of thyrotoxicosis, osteopenia is the result of an increase in bone formation and resorption, with a prevalence of resorption. In more severe thyrotoxicosis, the osteopenia is caused by a reduction in bone remodeling, with a predominance of bone resorption. Then, we compared the effects of T3 and GC-1, a thyromimetic that is selective for T3 receptor b (TRb), on bone of adult female mice. T3 treatment decreased tibial resistance, stiffness and resilience, while GC-1 increase these parameters and Tb.Th, showing that GC-1 improves bone quality. Considering the selectiveness of GC-1 for TRb, these findings suggest that TRb mediates mainly positive actions of T3 in the bone.

Made available in DSpace on 2014-07-29T15:21:57Z (GMT). No. of bitstreams: 1 Dissertacao_AndreaCastroPereira.pdf: 2370466 bytes, checksum: f8365afb8c90d3f08e392b9f49411d3e (MD5) Previous issue date: 2011-03-04 / The study of bone microarchitecture and its molecular aspects may provide new information for better understanding of "bone quality". Histomorphometry is a recommended reference method for bone-dimensional analysis. At the molecular level, possible changes in the process of resorption and bone formation has not been studied in different patterns of bone "normal." Objective: To analyze the correlation between clinical, radiographic and histomorphometric bone-molecular sites for dental implants in humans. Methods: The sample consisted of 44 sites of 32 volunteers implantable. These sites were classified according to three different methods: a classification based only on periapical and panoramic images (PP), the classification of Lekholm and Zarb, based on methods of diagnostic imaging in conjunction with the tactile perception of the surgeon during surgery and classification of Lindh. The bone specimens were removed with the use of trephine during the first drilling site for placement of dental implants. The samples were subjected to staining with hematoxylin-eosin and histomorphometric analysis to obtain the following histomorphometric parameters: trabecular thickness (Tb.Th), trabecular number, bone volume fraction (BV / TV), trabecular bone surface area by bone volume (BS / BV), bone surface fraction and trabecular separation (Tb.Sp). We also made the technique for analysis of proteins immunoistoquímica RANK, RANKL, OPG and osteocalcin (OC) in samples of bone tissue. Results: Rankings PP & L and Z correlated with BV / TV, BS / BV, Tb.Th and Tb.Sp. The classification of Lindh did not correlate with any histomorphometric parameter. L & Z show differences between types when compared to bone BV / TV, BS / BV, Tb.Th and Tb.Sp. We found a weak correlation between ratings PP / L & Z and the expression of regulators of bone metabolism (RANK, RANKL, OPG and OC). Conclusions: It may be that the subjective ratings conculir types of bone are influenced by aspects of histomorphometry and the regulatory molecules of bone remodeling seems not to exert influence in the morphology of the maxilla and mandible. / O estudo da microarquitetura óssea e dos seus aspectos moleculares podem trazer novas informações para a melhor compreensão da qualidade óssea . A histomorfometria é um método de referência recomendado para análise óssea bidimensional. A nível molecular, possíveis alterações das vias de reabsorção e formação óssea ainda não foram estudadas nos diferentes padrões de osso normal . Objetivo: Analisar a correlação entre aspectos clínico-radiográficos e histomorfométrico-moleculares de sítios ósseos para implantes dentários em humanos. Material e métodos: A amostra foi composta por 44 sítios implantáveis de 32 voluntários. Estes sítios foram classificados de acordo com 3 diferentes métodos: uma classificação baseada somente em imagens periapical e panorâmica (PP); a classificação de Lekholm e Zarb, baseada em métodos de diagnóstico por imagens em conjunto com a percepção tátil do cirurgião durante a cirurgia e a classificação de Lindh. Os espécimes ósseos foram removidos com o uso da trefina durante a primeira perfuração do sítio para colocação dos implantes dentários. As amostras foram submetidas à técnica de coloração com hematoxilina-eosina e análise histomorfométrica para obtenção dos seguintes parâmetros histomorfométricos: espessura trabecular (Tb.Th), número de trabéculas, fração de volume ósseo (BV/TV), área de superfície óssea trabecular pelo volume ósseo (BS/BV), fração de superfície óssea e separação trabecular (Tb.Sp). Também foi realizada a técnica da immunoistoquímica para análise das proteínas RANK, RANKL, OPG e Osteocalcina (OC) nas amostras de tecido ósseo. Resultados: As classificações PP e L&Z apresentaram correlação com BV/TV, BS/BV, Tb.Th e Tb.Sp. A classificação de Lindh não apresentou correlação com nenhum parâmetro histomorfométrico. L&Z demonstrou diferença entre os tipos ósseos quando comparado a BV/TV, BS/BV, Tb.Th e Tb.Sp. Foi encontrada uma fraca correlação entre as classificações PP/L&Z e a expressão dos reguladores do metabolismo ósseo (RANK, RANKL, OPG e OC). Conclusões: Pode-se conculir que as classificações subjetivas dos tipos ósseos são influenciadas pelos aspectos histomorfométricos e que as moléculas reguladoras da remodelação óssea parecem não exercer influência nos aspectos morfológicos da maxila e mandíbula.

Submitted by Jaqueline Silva (jtas29@gmail.com) on 2014-12-12T17:49:23Z No. of bitstreams: 1 Tese-Danilo Rocha Dias-2013.pdf: 12690993 bytes, checksum: 8af178ce9d242439a10d9aafdd18a329 (MD5) / Rejected by Jaqueline Silva (jtas29@gmail.com), reason: on 2014-12-12T17:49:32Z (GMT) / Submitted by Jaqueline Silva (jtas29@gmail.com) on 2014-12-12T19:43:01Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Tese-Danilo Rocha Dias-2013.pdf: 12690993 bytes, checksum: 8af178ce9d242439a10d9aafdd18a329 (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-12-16T09:25:37Z (GMT) No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Tese-Danilo Rocha Dias-2013.pdf: 12690993 bytes, checksum: 8af178ce9d242439a10d9aafdd18a329 (MD5) / Made available in DSpace on 2014-12-16T09:25:37Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Tese-Danilo Rocha Dias-2013.pdf: 12690993 bytes, checksum: 8af178ce9d242439a10d9aafdd18a329 (MD5) Previous issue date: 2013-07-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Bone characteristics influence surgical/prosthetic planning of implant treatment, but it is not clear their influence on longitudinal outcomes. This study aimed to investigate the association between jawbone microstructure and changes on marginal bone level (MBL) and implant stability (IS) after loading, in a 1-year follow-up. Forty-one volunteers received 97 dental implants, installed in bone sites classified from 1 to 4, according to Leckholm & Zarb (1985). Cortical bone thickness was measured on computed tomography images. Histomorphometric and microtomographic analyses were performed in bone specimens obtained by using a trephine bur, at first drilling. Peak insertion torque (PIT) and implant stability quotient (ISQ) measured by resonance frequency analysis (RFA) were registered at implant insertion. Periapical radiographs were standardized to measure the MBL, and were taken at three moments, when the ISQ was also measured: at uncovering stage, at loading and at 1-year follow-up. Agreement analysis between histomorphometry and microcomputed tomography (microCT) showed that these methods are complementary, but not interchangeably. Association tests revealed that ISQ changes were not affected by MBL changes. Bone type 4 (according L&Z) presented higher changes on ISQ, especially during osseointegration. Microstructure parameters (histomorphometric and microCT parameters) and cortical thickness did not influence ISQ changes and MBL changes. These results suggest that bone characteristics influence primary implant stability, but do not predict implant success after osseointegration. / Características do tecido ósseo influenciam o planejamento cirúrgico/protético dos implantes dentários, mas não está clara sua relação com o resultado longitudinal do tratamento com implantes. O objetivo deste estudo foi investigar a associação entre microestrutura óssea de sítios implantares da maxila e mandíbula, as alterações de nível ósseo marginal (MBL) e a estabilidade dos implantes (IS) até o período de 1 ano após a aplicação de carga oclusal. Quarenta e um pacientes receberam 97 implantes dentários, instalados em sítios ósseos classificados como tipos 1 a 4, de acordo com a classificação de Leckholm & Zarb (1985). A espessura de osso cortical foi mensurada em imagens de tomografia computadorizada. Análises microtomográficas e histomorfométricas foram realizadas em espécimes ósseos obtidos com trefina na primeira perfuração para instalação dos implantes. Torque de inserção final (PIT) e quociente de estabilidade do implante (ISQ) medido por análise de freqüência de ressonância (RFA) foram registrados durante a instalação dos implantes. Radiografias periapicais padronizadas para mensuração do MBL foram obtidas em tres momentos, quando novos registros do ISQ foram também realizados: durante a cirurgia de reabertura, na instalação das próteses e 1 ano após aplicação da carga oclusal. A análise de concordância entre os métodos de microtomografia computadorizada (microCT) e histomorfometria, mostrou que estes métodos são complementares, mas não intercambiáveis. Testes de associação mostraram que as alterações na IS não foram afetadas pelas alterações no MBL. Ossos classificados como tipo 4 apresentaram as maiores alterações da IS, principalmente durante a osseointegração. Os parâmetros microestruturais (parâmetros microtomográficos e histomorfométricos) e a espessura de cortical não influenciaram as alterações de IS e do MBL. Estes resultados sugerem que as características do sítio ósseo influenciam a estabilidade primária, mas não são preditores do sucesso dos implantes após a osseointegração.

La qualité osseuse est un paramètre important à prendre en compte lors des différents types de chirurgie mis en œuvre pour les interventions sur le rachis. Cependant, ce paramètre reste difficile à estimer in vivo du fait notamment de la difficulté à accéder à ce site anatomique. Ce travail porte sur le développement d'une technique ultrasonore permettant d'estimer la qualité osseuse en utilisant la réponse échographique d'une tige métallique insérée dans l'os et utilisée dans le cadre de la chirurgie du rachis. Des travaux expérimentaux montrent la faisabilité de notre approche in vitro. Une tige métallique similaire à celle utilisée en clinique est insérée dans des échantillons d'os trabéculaire perpendiculairement à l'axe du traducteur. Les réponses échographiques de la tige immergée dans l'eau et insérée dans l'os sont comparées, ce qui permet de déterminer la vitesse de propagation dans l'os (SOS, Speed of Sound), ainsi que la pente du coefficient d'atténuation en fonction de la fréquence (BUA, Broadband Ultrasonic Attenuation). Les résultats obtenus pour les 21 échantillons montrent i) une corrélation significative entre SOS et la fraction volumique d'os (BV/TV, R² = 0.6 et p < 0.001); et ii) une non-linéarité de la variation du BUA et BV/TV (R² = 0.22 et p<0.001). Des simulations numériques utilisant des éléments finis spectraux en 2D permettent de mieux comprendre la propagation ultrasonore et d'estimer la sensibilité des mesures à des erreurs de positionnement de la tige et du capteur. De plus, des simulations numériques par différences finies dans le domaine temporel en 3D permettent de mieux comprendre l'interaction entre une onde ultrasonore et le tissu osseux en comparant les résultats expérimentaux et numériques. Ce travail prouve la faisabilité de cette approche de caractérisation ultrasonore pour estimer la qualité osseuse, ce qui ouvre la voie à de possibles études cliniques dans le futur. / Bone quality is an important parameter which should be taken into account during the different types of surgical procedures used in spine surgery. However, this parameter remains difficult to be determined in vivo, mostly due to difficulties of positioning different sensors around this anatomical site. The aim of this work is to develop an ultrasonic technique allowing to assess bone quality using the echographic response of a metallic rod inserted in bone tissue and used in spine surgery. Experimental works show the feasibility of the technique in vitro. A metallic rod similar to the one used in the operating room is inserted in trabecular bone samples perpendicularly to the transducer axis. The echographic responses of the rod immersed in water and in bone tissue are compared, which allows to determine the wave velocity in bone tissue, as well as the slope of the attenuation coefficient as a function of frequency (BUA, broadband ultrasonic attenuation). The results obtained for the 21 samples show i) a significant correlation between SOS and bone volume fraction (BV/TV, R² = 0.6, p < 0.001); and ii) a non linear variation of BUA as a function of BV/TV (R² = 0.22, p<0.001).Numerical simulation using 2D spectral finite element simulation allows to better understand wave propagation and to estimate the sensitivity of the measurements to positioning errors of the rod and of the sensor. Moreover, 3-D finite difference time domain simulation allows to better understand the interaction between an ultrasonic wave and bone tissue by comparing the experimental and numerical results. This work proves the feasibility of this ultrasonic characterization approach to estimate bone quality, which opens the way to future clinical studies.

Ossos trabeculares possuem uma microestrutura porosa e podem ser modelados como um sólido elástico linear, heterogêneo e anisotrópico. A microtomografia tridimensional por raios-x (uCT) tem sido mundialmente utilizada para a caracterização de osso trabecular em pesquisas relacionadas à qualidade óssea e à doenças do metabolismo ósseo como a osteoporose. Na literatura há poucas investigações comparando as análises morfométricas 2D e 3D de osso trabecular. Nesta investigação amostras de osso trabeculares cilíndricas extraídas da cabeça femoral bovina foram utilizadas para a comparação dessas análises por \'mü\'CT. O software CT-Analyser foi utilizado para medidas em três direções (crânio-caudal, lateral-medial e anterior-posterior) de diversos parâmetros da microestrutura trabecular tais como espessura trabecular, separação trabecular, número trabecular e os autovalores do tensor de anisotropia (M). A comparação entre os valores dos parâmetros medidos por análises morfométricas 2D e 3D foi realizada pelo teste-t pareado com nível de significância p < 0,05 e por correlação linear de Pearson. Os autovalores da matriz M mostram que a microestrutura trabecular bovina tem uma tendência para a simetria transversalmente isotrópica. Os resultados obtidos mostram que a microtomografia tridimensional por raios-X é uma técnica de grande potencial para caracterização da qualidade óssea gerando bons parâmetros para o diagnóstico de doenças do metabolismo ósseo. / Trebecular bones have a porous microstructure and can be modeled as a linear elastic solid, heterogenous and anisotropic. The x-ray tridimensional microtomography (\'mü\'CT) has been worldwide used for the assessment of trabecular bone in investigations related to bone quality and aimed to the diagnostic of bone metabolic diseases such as osteoporosis. In the literature few investigations have compared the 2D and 3D morphometric analysis of trabecular bone. In this investigation cylindrical trabecular bone samples were harvested from bovine head femur to carry out that comparison by \'mü\'CT. The CT-Analyser software was used to measure in three directions (superior-inferior, lateral-medial and anterior-posterior) several microstructural trabecular parameters such as trabecular thickness, trabecular separation, trabecular number and the eigenvalues of the fabric tensor (M). The comparison between the parameters values measured by 2D and 3D morphometric analysis was performed by the paired-sample t test with a level of significance p < 0,05 and the Pearson\'s linear correlation. The eigenvalues show that the bovine trabecular microstructure has a tendence to transverse isotropy symmetry. The results show that x-ray tridimensional microtomography (\'mü\'CT) is a technique of great potential for characterization of generating good bone quality parameters for the diagnosis of diseases of bone metabolism.

<p> This thesis focuses on an examination of cortical and trabecular bone density and geometry at the radius and tibia in postmenopausal women, primarily women with history of breast carcinoma, while also assessing musculoskeletal changes in postmenopausal breast cancer patients after treatment with the Aromatase Inhibitor, Anastrozole. The first sub-study is an investigation of the reproducibility of the pQCT measurement parameters at the radius and tibia in healthy pre-and postmenopausal women. Results indicated that the reproducibility was good at the radius and even better at the tibia for all parameters measured. The second study is an appraisal of the level of osteoporosis knowledge in a cohort of postmenopausal women. The participants were assessed via the Facts on Osteoporosis Quiz, a well validated questionnaire, and the data revealed significantly lower test scores among the breast cancer subjects in comparison with healthy postmenopausal women. In the remaining group of studies, pQCT technology was utilized to describe trabecular and cortical bone at the radius and tibia in postmenopausal women and women with a history of breast carcinoma whom had been prescribed Anastrozole. The following measurement sites were significantly lower in the breast cancer subjects: TOT_DEN and TOT_CNT at the 4% radius; CRT_DEN, TOT_CNT, and CRT_CNT at the 20% radius; TOT_DEN at the 4% tibia; and CRT_DEN at the 38% tibia. With respect to time on Anastrozole, TOT_CNT at the 4% radius (r=-0.36); TOT_CNT (r=-0.33), CRT_CNT (r=-0.34) and CRT_DEN (r=-0.44) at the 20% radius; and CRT_DEN (r=-0.39) and CRT_CNT (r=-0.27) at the 38% tibia were significantly negatively correlated with days on Anastrozole. Furthermore, after two years of Anastrozole treatment in a small cohort of breast cancer subjects, there was a significant decrease in CRT_DEN (p=0.025) at the 20% diaphyseal radius and also at the 38% diaphyseal tibia (p=0.051). Together, the sub-studies that comprise this thesis demonstrate that there are noteworthy deficiencies in osteoporosis knowledge among postmenopausal women, particularly those with a history of breast carcinoma, and yet, these are the same women that have an increased need to understand the preventative and treatment options regarding this disease as they demonstrate reduced bone density at all measurement sites. It also appears that time on Anastrozole primarily affects cortical bone density in these women. In summary, this thesis provides novel details regarding cortical bone in breast cancer subjects and emphasizes the need for a normative database of bone quality parameters at different skeletal sites in order to gain a better understanding of the utility of each skeletal site with regard to fracture risk prediction. </p> / Thesis / Doctor of Philosophy (PhD)

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