L’opération morphologique de squelettisation transforme chaque objet d’une image en une forme linéique qui préserve la topologie de ce dernier (propriété d’homotopie). Elle est largement utilisée en biométrie mais aussi dans la reconnaissance des caractères ainsi que pour l’extraction de la microarchitecture osseuse. L’objectif de cette thèse est de développer une méthode de squelettisation appliquée directement sur les niveaux de gris de l’image, ce qui a pour large avantage de s’affranchir de prétraitement comme la binarisation. Une revue des méthodes de squelettisation en niveaux de gris permet de constater que l’amincissement est l’une des approches les plus usitées de par sa propriété d’homotopie. Cependant, cette approche est sensible au bruit de l’image et produit des squelettes sur-connectés. Un premier paramétrage de l’amincissement a été proposé dans la littérature afin d’abaisser des configurations de pixels liées au bruit. La première contribution de ce travail est de proposer un ajustement de ce paramètre basé sur une décision statistique. Il s’agit d’identifier les tests d’hypothèses correspondants aux différentes configurations d’abaissement en vue de fixer ce paramètre de façon locale. Ceci conduit à la mise en place d’une squelettisation appelée Self Contrast Controlled Thinning (SCCT) puisque robuste au bruit tout en s’adaptant automatiquement au contraste de l’image. La squelettisation SCCT est rendue accessible aux domaines d’application grâce à son implantation optimisée basée sur les files d’attente hiérarchiques. Ayant noté le peu d’efforts consacrés à l’évaluation de la squelettisation en niveaux de gris, la deuxième contribution de ce travail est de proposer un protocole visant à évaluer l’opération de squelettisation sur la base des propriétés requises à savoir la préservation de la topologie et de la géométrie. Ce protocole est déroulé sur une base d’images synthétiques et nous permet de comparer notre approche à celles de la littérature. La troisième contribution est de proposer une structuration du squelette en graphe donnant accès aux descripteurs structurels et morphométriques des objets étudiés en vue d’une exploitation du squelette par les experts des domaines d’applications. Dans le cadre du projet Voxelo coordonné par le laboratoire B2OA de l’Université Paris Diderot, cette structuration est exploitée pour extraire les descripteurs de la qualité de la microarchitecture osseuse à partir d’images RX haute résolution. / Skeletonization is an image transformation that aims to represent objects by their medial axis while preserving their topological characteristics (homotopy). It is widely used in biometrics, character recognition and also in the extraction of bone microarchitecture. The objective of this thesis is to develop a skeletonization method applied directly on image gray levels. This has the large advantage of freeing the operation from preprocessing techniques such as binarization. A review of grayscale skeletonization methods shows that the morphological thinning is one of the most used approaches for its topology preservation property. However, this approach is sensitive to image noise and produces inexploitable skeletons. A first parameterization of the thinning process has been proposed in the literature to reduce noise-related information. The first contribution of this work is to propose an adjustment of this parameter based on a statistical decision. To this end, a hypothesis test is identified for each lowering criterion in order to set the thinning parameter locally. This leads us to propose the Self Contrast Controlled Thinning method SCCT that is robust to noise and is automatically adjusted to image contrast. The SCCT is made available to application domains through its optimized implementation based on hierarchical queues. Noticing the lack of efforts to assess grayscale skeletonization, the second contribution of this work is to propose a quantitative evaluation protocol assessing skeletonization with regard to its fundamental properties that are namely the preservation of topology and geometry. This protocol is conducted over a synthetic images database and allows us to compare SCCT to approaches from the literature. The third contribution consists in structuring the skeleton into a graph that gives access to objects structural and morphometric descriptors and enables the exploitation of the skeleton by experts from various fields of application. This structuring is applied in the context of Voxelo project which is coordinated by B2OA laboratory of the University Paris Diderot. In this context, descriptors of bone microarchitecture quality are extracted from X-ray high resolution images.

La microarchitecture osseuse est un des déterminants de la qualité osseuse qui peut maintenant être évaluée in vivo au radius et au tibia distaux avec une résolution isotropique de 82μm par un nouveau scanner à haute résolution (XtremeCT, SCANCO Medical AG). Par ailleurs, l'utilisation d'analyse en éléments finis sur les volumes 3D obtenus permet d'évaluer les propriétés biomécaniques de l'os comme la résistance osseuse. Nous avons montré qu'il s'agissait d'une technique prometteuse pour évaluer la densité, la microarchitecture et les propriétés biomécaniques osseuses au niveau des sites périphériques, notamment parce que ces mesures étaient associées chez la femme avec des fractures ostéoporotiques de toutes sortes. Nous avons également montré que les mêmes mesures étaient tout aussi pertinentes chez l'homme, alors qu'il est moins sujet à l'ostéoporose. Les résultats étaient associés aux fractures ostéoporotiques de toutes sortes, notamment les fractures vertébrales. L'analyse en éléments finis permet donc la mesure in vivo de la résistance osseuse, ce qui pourrait fournir des informations sur la fragilité osseuse et le risque de fracture non accessible par les seules mesures de densité ou de microarchitecture osseuse.

L’ostéoporose est une maladie fréquente et généralisée du squelette qui se caractérise par une perte de masse osseuse et des altérations de la structure des os. Ces variations des propriétés osseuses, observées à diverses échelles et associées à une augmentation du contenu adipeux de la moelle, témoignent d’une plus grande fragilité du squelette. Ces modifications sont cependant différentes en fonction du site. Cette variation du contenu adipeux médullaire, rapportée notamment dans les os longs du squelette appendiculaire, semble jouer un rôle crucial dans la survenue de l’ostéoporose. Néanmoins, ces altérations ostéo-médullaires, aussi bien quantitatives que qualitatives, sont controversées et peu documentées au niveau des maxillaires, la mandibule en particulier. Le but de notre étude est d’évaluer, au cours du vieillissement et dans un modèle d’ostéoporose (ratte adulte ovariectomisée), les relations entre les variations du contenu adipeux médullaire et la microarchitecture osseuse en site mandibulaire en comparaison avec un site de référence, le tibia. La microarchitecture osseuse, la quantité et la répartition du contenu adipeux médullaire après marquage au tétroxyde d’osmium ont été analysées par microtomographie à rayons X dans la mandibule dentée (os alvéolaire) et non dentée (condyle). Au cours du vieillissement, aucune altération des paramètres osseux et médullaires n’a été mise en évidence. En revanche, le déficit hormonal en oestrogènes induit par ovariectomie conduit à une perte osseuse plus marquée (+35%) dans le tibia que dans la mandibule, associée à des modifications microarchitecturales et adipeuses médullaires site-spécifiques. En effet, en comparaison avec le tibia, un faible contenu adipeux (<10% de moelle) est retrouvé dans le secteur denté (alvéolaire) ainsi que non denté (condyle). A la différence du tibia, au sein duquel un effet de « clustering » des adipocytes est observé à la surface osseuse trabéculaire, le contenu adipeux mandibulaire est réparti de manière homogène dans les espaces médullaires avec très peu de contact avec la surface osseuse trabéculaire. En conclusion, nos résultats indiquent une perte osseuse modérée dans la mandibule par rapport au tibia associée à une augmentation du contenu adipeux médullaire tardive dont la répartition au sein des espaces médullaires n’est pas modifiée à la différence du tibia. Nous émettons l’hypothèse qu’une activité de remodelage et des sollicitations biomécaniques différentes puissent expliquer les spécificités physiopathologiques observées en site mandibulaire. D’autres études seront nécessaires pour préciser l’impact de telles modifications sur la qualité osseuse à l’échelle moléculaire et élémentaire, ainsi que pour préciser les mécanismes de dialogues entre les ostéoblastes et les adipocytes. / Osteoporosis is a common disease of the skeleton characterized by a loss of bone mass and changes in bone structure. These variations in bone properties, observed at various scales and associated with an increase in the bone marrow adipose tissue (BMAT) content, indicate a greater fragility of the skeleton in a site-specific manner. This variation in the BMAT content, reported in some skeletal sites, seems to play a crucial role in the occurrence of osteoporosis. Nevertheless, these bone and marrow alterations, both quantitative and qualitative, are controversial and still poorly documented in the jaw bones, the mandible in particular.The aim of our study was to investigate, during aging and in a rodent model of osteoporosis (adult ovariectomized rat), the relationships between the changes in the bone microstructure, the marrow fat content and its distribution in the mandibular site in comparison with a reference site, the tibia. The bone microstructure, the bone marrow fat content and its distribution after osmium tetroxide staining were analyzed by a specific X-ray microfocus tomography approach in the mandible in the teeth-bearing area (alveolar bone) and in the condyle. During aging, neither bone nor bone marrow alterations have been observed. In contrast, estrogen deficiency did lead to more important bone loss (+35%) in the tibia than in the mandible associated with site-specific microstructural and BMAT modifications. Indeed, in comparison with the tibia, a low BMAT content (<10% of marrow volume) was found in the alveolar bone as well as in the condyle. Compared to tibia which reveals a clustering of the marrow adipocytes at the trabecular bone surface, the mandibular BMAT content was homogeneously distributed and located further away with almost no contact with the trabecular bone surface. In conclusion, our results indicate a moderate bone loss in the mandible compared to the tibia associated with an increase in the BMAT content whose distribution within the marrow spaces is not modified in contrast to tibia. We hypothesize that a differential bone turn-over rate, biomechanical stress may explain in part the mandibular physiopathological specificities reported. Further studies will be needed to precise the impact of such alterations on bone quality at the molecular and elemental level, as well as to depict the mechanisms of dialog between osteoblasts and adipocytes.

L'ostéoporose est une maladie du squelette caractérisée par une dégradation de la qualité osseuse conduisant à une majoration du risque fracturaire. Le seul examen permettant actuellement de prédire ce risque est l'ostéodensitométrie à double rayonnement X (DXA) par la mesure de la densité minérale osseuse (DMO). Cependant, la DMO seule ne rend compte que de 40 à 70% de la variation de la résistance mécanique osseuse. Les 3 buts ce travail étaient : 1/ d'évaluer les rôles respectifs de la microarchitecture corticale et trabéculaire dans le comportement mécanique vertébral, 2/ d'évaluer le rôle propre de l'hétérogénéité de la microarchitecture trabéculaire et 3/ de décrire le comportement mécanique vertébral post-fracturaire et d'en identifier les déterminants. Nous montrons que la mesure de l'épaisseur de la corticale antérieure et de son rayon de courbure ainsi que la détermination de la variation régionale de la microarchitecture trabéculaire améliorent significativement la prédiction du risque fracturaire. Il existe une variation marquée du comportement mécanique vertébral après une fracture de grade 1 de Genant. La microarchitecture osseuse, et non la masse osseuse, explique les propriétés mécaniques vertébrales plastiques et élastiques post-fracturaires.

The objective of this study was to examine the link between radiographic measures of bone quality and total knee implant migration as measured by radiostereometric analysis (RSA). Two uncemented total knee arthroplasty studies (n=65) with RSA and bone mineral density (BMD) exams up to two years post surgery, and one study with cemented total knees with one year RSA data (n=18) were examined. Radiograph image texture analysis was used to characterize the bone microarchitecture, and a feasibility study was conducted to determine if a given x-ray machine could be used to obtain bone mineral density at the same time as the RSA exams. Random ForestTM ensemble classification tree statistical models classified patients into groups based on implant migration with a range of cut-points. Models based on bone texture parameters measured from the two year radiographs had a sensitivity of 87.5% and specificity of 80% when classifying patients who had more than 0.3mm maximum total point motion (MTPM) at two years using the one year exam as reference. Other cut-points were examined, with models generally having a lower specificity if the acceptable migration was smaller, and lower sensitivity if higher migrations were tolerable. In a predictive model, post-operative bone texture could be used to create a model with a sensitivity of 75% and a specificity of 80% when predicting those subjects with cemented implants who went on to more than 0.4mm total migration by one year. Bone mineral density of the proximal tibia, as determined by clinical scanners, was not found to increase the accuracy of implant migration group classification. An empirical fit to central regions of a purposed-built cross-wedge calibration phantom returned residuals of less than ±1.5% for the bone-equivalent thicknesses. The coefficient of variation of the region greyscale values in three images spread over three days is under 4%, showing the stability of the system to hold a calibration between phantom exams and patient scans. Scatter and dynamic range issues will need to be considered for an accurate calibration across the full range of areal bone mineral densities in the distal femur and proximal tibia.

A microtomografia computadorizada (uCT) é uma técnica de ensaio não destrutivo, frequentemente utilizada no estudo da estrutura interna de ossos, com uma resolução espacial da ordem de mícrons. Neste trabalho, seis pares de amostras ósseas (fêmur de rato) foram estudados através da uCT. Os ensaios foram conduzidos na presença ou não de filtros de alumínio (espessura de 0,25; 0,50 e 0,75 mm), utilizando-se três níveis de resolução (33,3; 15,0 e 9,5 um). Os parâmetros de arquitetura óssea BS (área óssea da amostra), BV (volume ósseo da amostra), TS (área superficial da amostra), TV (volume da amostra), BV/TV (razão entre o volume ósseo e o volume da amostra), BS/BV (razão entre a área óssea da amostra e o volume ósseo da amostra), Tb.N (densidade trabecular), Tb.Th (espaçamento entre as trabéculas), Tb.Sp (separação trabecular), conectividade e anisotropia foram determinados através das análises em duas (2D) e/ou três (3D) dimensões. A comparação entre os valores dos parâmetros obtidos através dessas análises foi realizada através do teste t pareado e da correlação de Pearson. Com base nos resultados, foi possível determinar a influência da resolução da imagem na qualidade dos parâmetros da arquitetura óssea obtidos através das análises 2D e/ou 3D. Os dados mostram que a presença de filtro de alumínio também afeta a qualidade desses parâmetros. Assim, os melhores resultados são obtidos com resolução máxima e filtro de alumínio com espessura de 0,25 ou 0,50 mm. / X-Ray Computed Microtomography (uCT) is a nondestructive technique used to study the internal structure of bones with a spatial resolution of the order of microns. In this study, six pairs of bone samples (femur mouse) were studied by uCT. The tests were conducted in the absence or presence of aluminum filters (thickness of 0.25, 0.50 and 0.75 mm), using three different resolution levels: 33.3, 15.0 and 9.5 um. The bone architecture parameters BS (surface area of the trabecular bone), BV (bone volume of the sample), TS (surface area of the sample), TV (sample volume), BV/TV (bone volume fraction), BS/BV (ratio bone surface and volume), Tb.N (trabecular density), Tb.Th (trabecular spacing), Tb.Sp (trabecular separation), connectivity and anisotropy were determined by 2D and/or 3D analysis. The comparison between the values of the parameters obtained in these analysis was performed using the t test and Pearson correlation. Based on the results it was possible to determine the influence of image resolution on the quality of the bone architecture parameters obtained in the 2D and/or 3D analysis. The data also show that the presence of aluminum filter affects the quality of these parameters. Thus, the best results are obtained with maximum resolution and aluminum filter with a thickness of 0.25 or 0.50 mm.

A microtomografia computadorizada (uCT) é uma técnica de ensaio não destrutivo, frequentemente utilizada no estudo da estrutura interna de ossos, com uma resolução espacial da ordem de mícrons. Neste trabalho, seis pares de amostras ósseas (fêmur de rato) foram estudados através da uCT. Os ensaios foram conduzidos na presença ou não de filtros de alumínio (espessura de 0,25; 0,50 e 0,75 mm), utilizando-se três níveis de resolução (33,3; 15,0 e 9,5 um). Os parâmetros de arquitetura óssea BS (área óssea da amostra), BV (volume ósseo da amostra), TS (área superficial da amostra), TV (volume da amostra), BV/TV (razão entre o volume ósseo e o volume da amostra), BS/BV (razão entre a área óssea da amostra e o volume ósseo da amostra), Tb.N (densidade trabecular), Tb.Th (espaçamento entre as trabéculas), Tb.Sp (separação trabecular), conectividade e anisotropia foram determinados através das análises em duas (2D) e/ou três (3D) dimensões. A comparação entre os valores dos parâmetros obtidos através dessas análises foi realizada através do teste t pareado e da correlação de Pearson. Com base nos resultados, foi possível determinar a influência da resolução da imagem na qualidade dos parâmetros da arquitetura óssea obtidos através das análises 2D e/ou 3D. Os dados mostram que a presença de filtro de alumínio também afeta a qualidade desses parâmetros. Assim, os melhores resultados são obtidos com resolução máxima e filtro de alumínio com espessura de 0,25 ou 0,50 mm. / X-Ray Computed Microtomography (uCT) is a nondestructive technique used to study the internal structure of bones with a spatial resolution of the order of microns. In this study, six pairs of bone samples (femur mouse) were studied by uCT. The tests were conducted in the absence or presence of aluminum filters (thickness of 0.25, 0.50 and 0.75 mm), using three different resolution levels: 33.3, 15.0 and 9.5 um. The bone architecture parameters BS (surface area of the trabecular bone), BV (bone volume of the sample), TS (surface area of the sample), TV (sample volume), BV/TV (bone volume fraction), BS/BV (ratio bone surface and volume), Tb.N (trabecular density), Tb.Th (trabecular spacing), Tb.Sp (trabecular separation), connectivity and anisotropy were determined by 2D and/or 3D analysis. The comparison between the values of the parameters obtained in these analysis was performed using the t test and Pearson correlation. Based on the results it was possible to determine the influence of image resolution on the quality of the bone architecture parameters obtained in the 2D and/or 3D analysis. The data also show that the presence of aluminum filter affects the quality of these parameters. Thus, the best results are obtained with maximum resolution and aluminum filter with a thickness of 0.25 or 0.50 mm.

abstract: Coarse Grain Reconfigurable Arrays (CGRAs) are promising accelerators capable of achieving high performance at low power consumption. While CGRAs can efficiently accelerate loop kernels, accelerating loops with control flow (loops with if-then-else structures) is quite challenging. Techniques that handle control flow execution in CGRAs generally use predication. Such techniques execute both branches of an if-then-else structure and select outcome of either branch to commit based on the result of the conditional. This results in poor utilization of CGRA s computational resources. Dual-issue scheme which is the state of the art technique for control flow fetches instructions from both paths of the branch and selects one to execute at runtime based on the result of the conditional. This technique has an overhead in instruction fetch bandwidth. In this thesis, to improve performance of control flow execution in CGRAs, I propose a solution in which the result of the conditional expression that decides the branch outcome is communicated to the instruction fetch unit to selectively issue instructions from the path taken by the branch at run time. Experimental results show that my solution can achieve 34.6% better performance and 52.1% improvement in energy efficiency on an average compared to state of the art dual issue scheme without imposing any overhead in instruction fetch bandwidth. / Dissertation/Thesis / Masters Thesis Electrical Engineering 2014

Submitted by RICARDO DE PAULA DE ALMEIDA null (ricardo_edfisica@outlook.com) on 2017-09-05T19:40:32Z No. of bitstreams: 1 Dissertação Ricardo de Paula de Almeida_ Corrigida.pdf: 1537601 bytes, checksum: 7c006e1b262a9101de58abe1ee699b5f (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-09-05T19:57:20Z (GMT) No. of bitstreams: 1 almeida_rp_me_araca.pdf: 1537601 bytes, checksum: 7c006e1b262a9101de58abe1ee699b5f (MD5) / Made available in DSpace on 2017-09-05T19:57:20Z (GMT). No. of bitstreams: 1 almeida_rp_me_araca.pdf: 1537601 bytes, checksum: 7c006e1b262a9101de58abe1ee699b5f (MD5) Previous issue date: 2017-07-12 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A diminuição de massa óssea concomitante à progressão da idade resulta em maior incidência de fraturas, devido a mudanças microarquiteturais que são determinantes importantes para a qualidade óssea. Concomitantemente, mecanismos moleculares que agem na manutenção celular como a autofagia podem estar relacionados ao “turnover” ósseo no período do envelhecimento, sendo estes mecanismos relacionados ao processo de osteopenia/osteoporose. Neste estudo foram avaliados os efeitos do treinamento de força (TF) na microestrutura do colo do fêmur de ratas Wistar adultas (7 meses) e velhas (21 meses) submetidas ou não ao programa de exercício físico e distribuídas nos grupos: adultas não exercitadas (A/NEX); adultas exercitadas (A/EX); velhas não exercitadas (V/NEX) e velhas exercitadas (V/EX). O treinamento de força foi realizado utilizando-se escada com carga atrelada à cauda dos animais; 3 vezes por semana durante período de 120 dias. Resultados obtidos por microtomografia computadorizada (μCT) após este período demonstraram que o TF foi capaz de aumentar a espessura (Ct. Th (mm); V/EX vs A/EX p = 0,7863), momento polar de inércia médio (pMOI (mm4); A/NEX vs A/EX p = 0,0362; V/NEX vs V/EX p = 0,0032) e reduzir a porosidade da região cortical do colo do fêmur (Ct. Po (%); V/NEX vs V/EX p = 0,0406), causando aumento na área cortical total (Tt.Ar (mm²); V/NEX vs V/EX p = 0,0406). No osso trabecular notou-se maior fração do volume ósseo (BV/TV (%); V/NEX vs V/EX p = 0,006); espessura trabecular (Tb.Th (mm); V/NEX vs V/EX p = 0,0069; V/EX vs A/EX p<0,0001); número de trabéculas (Tb.N (1/mm) V/NEX vs V/EX p = 0,0004) e grau de anisotropia ( DA V/NEX vs V/EX p = 0,0088). Estas modificações resultaram em redução do espaçamento trabecular (Tb.Sp (mm) V/EX vs A/EX p = 0,0382) e porosidade trabecular (Tb.Po (%) V/NEX vs V/EX p = 0,0006). Além destes parâmetros da estrutura cortical e trabecular, foram avaliados: capacidade de carregamento voluntário máximo (CCVM); peso corporal, do útero e do tecido adiposo retroperitoneal; biomarcadores para fosfatase alcalina plasmática (FAL) e fosfatase ácida resistente à tartarato sérica (TRAP); densidade mineral óssea areal (DMOa), Western blot para beclina-1, LC3, sequestossoma-1/p62 (SQSTM-1/p62), AKT, ERK1//2, pAKT (Ser473), pERK (Thr202/ Tyr204); e imunoistoquímica (IHQ) para RUNX-2, FAL, TRAP, Osteocalcina (OCN) e beclina-1. As dosagens plasmáticas evidenciaram aumento na atividade da FAL após a realização do TF (A/NEX vs A/EX p = 0,0002). Concentrações plasmáticas de TRAP não apresentaram alterações significantes. Análises de marcadores autofágicos mostraram maior expressão para beclina-1 em A/EX e V/EX. LC3 também obteve elevada expressão em A/EX, mas em V/EX sua expressão foi menor. A expressão de SQSTM1/p62 foi reduzida após a realização do TF nas ratas A/EX e V/EX. AKT total (t-AKT) e AKT fosforilada (pAKT-Ser473) demonstrou expressão mais alta em A/EX comparados à A/NEX. Por outro lado, em V/EX, a fosforilação foi reduzida em Ser473 quando comparados à V/NEX, mas t-AKT permaneceu inalterada em ambos. Resultados para ERK1/2 demonstraram redução na expressão em A/EX comparados à A/NEX, mas em V/EX sua expressão foi melhorada comparados à V/NEX. A fosforilação de ERK em Thr202 foi aumentada em A/EX em relação à A/NEX, mas em ratas velhas não houveram modificações. No sítio Tyr204 também houve elevada fosforilação em A/EX comparados à A/NEX, mas foi reduzida em V/EX comparados à V/NEX. A imunomarcação de RUNX-2, FAL, OCN e beclina-1 foi menor em V/NEX mas em V/EX a marcação aumentou assemelhando -se à A/EX. TRAP, elevada em V/NEX, mostrou -se reduzida em V/EX. Em suma, neste estudo nós demonstramos a atuação do TF no metabolismo ósseo de ratas no período da periestropausa com resposta integrada entre exercício e idade. Este estudo também demonstrou que proteínas importantes relacionadas à regulação autofágica e metabolismo ósseo podem ser potencialmente alteradas pelo TF. Nossos resultados evidenciam atuação do TF na manutenção da massa óssea mostrando que essa modalidade de exercício pode prevenir e/ou diminuir danos causados pela osteoporose durante o estágio do envelhecimento. / The decrease in bone mass concomitant with the progression of age results in a higher incidence of fractures, due to microarchitectural changes that are important determinants of bone quality. Concomitantly, molecular mechanisms that act in cellular maintenance such as autophagy may be related to bone turnover in the aging period, and these mechanisms are related to the osteopenia/osteoporosis process. In this study were evaluated, the effects of strength training (ST) on the femoral neck microstructure of adult (7 months) and old (21 months) female Wistar rats submitted or not to the physical exercise program and distributed in the following groups: non-exercised adult groups (A/NEX); exercised adults (A/EX); non-exercised old (O/NEX) and old exercised (O/EX). Strength training was performed using a ladder with load attached to the tail of the animals; 3 times a week for a period of 120 days. Results obtained by computerized microtomography (μCT) after this period demonstrated that the ST was able to increase the thickness (Ct.Th (mm), O/EX vs A/EX p = 0.7863), mean polar moment of inertia (mm4), A/NEX vs A/EX p = 0.0362, O/NEX vs O/EX p = 0.0032) and reduce the porosity of the cortical region of the femoral neck (Ct Po (%); O/NEX vs O/EX p = 0.0406), causing increase in the total cortical area (Tt.Ar (mm²); O/NEX vs O/EX p = 0.0406). In trabecular bone, a higher fraction of bone volume was observed (BV / TV (%), O/NEX vs O/EX p = 0.006); (Tb.Th (mm); O/NEX vs O/EX p = 0.0069; O/EX vs A/EX p <0.0001); number of trabeculae (Tb.N (1/mm) O/NEX vs O/EX p = 0.0004) and degree of anisotropy (DA O/NEX vs O/EX p = 0.0088). These changes resulted in a reduction in trabecular spacing (Tb.Sp (mm) O/EX vs A/EX p = 0.0382) and trabecular porosity (Tb.Po (%) O/NEX vs O/EX p = 0.0006 ). In addition to these parameters of the cortical and trabecular structure, the following were evaluated: maximum voluntary carrying capacity (MVCC); body weight, uterus and retroperitoneal adipose tissue; biomarkers for plasmatic alkaline phosphatase (ALP) and serum tartrate resistant acid phosphatase (TRAP); Western blot for beclin-1, LC3, sequestosome-1/p62 (SQSTM-1 / p62), AKT, ERK1/2, pAKT (Ser473), pERK (Thr202/Tyr204) and immunohistochemistry (IHC) for RUNX-2, ALP, TRAP, osteocalcin (OCN) and beclin-1. Plasma dosages showed an increase in ALP activity after ST (A/NEX vs A/EX p = 0.0002). Plasmatic concentrations of TRAP did not show significant alterations. Analyzes of autophagic markers showed higher expression for beclin-1 in A/EX and O/EX. LC3 also had higher expression in A/EX, but in O/EX its expression was lower. Expression of SQSTM1/p62 was reduced after ST in the A/EX and O/EX rats. Total AKT (t-AKT) and phosphorylated AKT (pAKT-Ser473) demonstrated higher expression in A/EX compared to A/NEX. On the other hand, in O/EX, phosphorylation was reduced in Ser473 when compared to O/NEX, but t-AKT remained unchanged in both. Results for ERK1/2 demonstrated reduction in A/EX expression compared to A/NEX, but in O/EX their expression was improved compared to O/NEX. ERK phosphorylation in Thr202 was increased in A/EX relative to A/NEX, but in old rats there were no changes. At the Tyr204 site there was also high A/EX phosphorylation compared to A/NEX, but was reduced in O/EX compared to O/NEX. Immunostaining of RUNX-2, FAL, OCN and beclin-1 was lower in O/NEX but in O/EX the labeling increased resembling A/EX. TRAP, high in O/NEX, was reduced in O/EX. In summary, in this study we demonstrated the action of ST in bone metabolism of rats in periestropause period with integrated response between exercise and age. This study also demonstrated that important proteins related to autophagic regulation and bone metabolism may be potentially be altered by ST. Our results demonstrate the role of ST in maintaining bone mass, showing that this exercise modality can prevent and/or reduce osteoporosis damage during the aging stage.

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