Orientador: Jorge Kennety Silva Formiga / Coorientadora: Vivian Silveira dos Santos Silva Bardini / Banca : João Maurício Ferraz da Silva / Banca: Denilson Paulo Souza dos Santos / Resumo: Os modelos matemáticos utilizados atualmente para análise variação da densidade óssea quando submetido a estímulos mecânicos, consideram apenas carregamentos estáticos ou a variação dentro de um curto espaço de tempo e permanecendo estático novamente. Esse artigo tem o objetivo de desenvolver dois novos modelos que permitam simular o comportamento do tecido ósseo de remodelagem e determinar as faixas de subcarga e sobrecarga onde ocorrem a reabsorção óssea, quando submetido a estímulos mecânicos variados oscilando no tempo. Tradicionalmente os estudos realizados para determinação da variação da densidade óssea, vem utilizando um modelo adotando uma equação diferencial ordinária (EDO) para analisar essa variação. A partir do modelo dessa EDO, foram desenvolvidas duas novas equações matemáticas para simular o comportamento do tecido ósseo quando submetido à estímulos mecânicos variados no tempo. A primeira equação utiliza uma variação da tensão seguindo o padrão de oscilação de uma onda senoidal e a segunda equação utiliza um padrão de onda resultante da combinação linear entre seno e cosseno. A resolução dessa EDO foi feita utilizando o método de Runge-Kutta de 5ª ordem, um integrador de maior precisão e permitindo uma melhor análise do comportamento do tecido ósseo através dos resultados obtidos com maior precisão para diversos níveis de tensão. A análise dos resultados obtidos através das simulações matemáticas empregando três tipos de carregamentos, estático, variável de ac... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract : The mathematical models currently used for bone density variation analysis when subjected to mechanical stimuli, consider only static loading or variation within a short time and remaining static again. This article aims to develop two new models that allow simulating the behavior of bone remodeling tissue and determine the underload and overload ranges where bone resorption occurs when subjected to varying mechanical stimuli oscillating over time. Traditionally, studies performed to determine bone density variation have been using a model using an ordinary differential equation (ODE) to analyze this variation. From the model of this ODE, two new mathematical equations were developed to simulate the behavior of bone tissue when subjected to varying mechanical stimuli over time. The first equation uses a voltage variation following the sine wave oscillation pattern and the second equation uses a wave pattern resulting from the linear combination of sine and cosine. The resolution of this ODE was performed using the 5th order Runge-Kutta method, a more accurate integrator and allowing a better analysis of bone tissue behavior through the results obtained with greater precision for various stress levels. The analysis of the results obtained through mathematical simulations employing three types of loads, static, variable according to the oscillation of a sine wave and variable through the oscillation of a sine-cosine wave, demonstrated that the behavior of bone tissue in relation to the stimuli Mechanics vary by type of loading. The stress levels applied for the three simulations were the same, but the bone remodeling behavior response was different for each type of loading. The resorption tension range, remodeling tension range and overload range change according to the type of loading applied, demonstrating that bone tissue behavior may ....(Complete abstract click electronic access below) / Mestre

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Osteoporosis affects the human skeleton through the direct effects of the disease on the function and structure of bone. Individuals who are affected by osteoporosis may be subject to serious fractures and it is estimated that annually approximately 1.5 million fractures can be attributed to this disease [1]. The disease is categorized as the direct side effect of increased bone porosity and bone loss and is directly linked to estrogen deprivation [2]. Animal models are often used to make initial conclusions about the effects of the disease or pharmacological treatments. In this study, sheep were chosen as a representative animal model due to their similar metabolic characteristics to that of a human. Like most animals, the ovine does not undergo a natural menopause and an ovariectomy was necessary to replicate the condition. The study objective was to quantify compact bone density present in ovine at three months post ovariectomy. The study included 112 ovine separated into different treatment groups. The treatment groups were separated into 4 groups of 28 based on season of surgery: autumn, winter, spring, and summer. Each seasonal group was further divided into 2 groups of 14; the first group underwent an ovariectomy; and the second group underwent a sham surgery, in which the ovaries were visualized and handled but left in the abdomen. One group was sacrificed 3 months post operatively and the other group was sacrificed at 12 months post operatively. This study specifically looks at ewe sacrificed at 3 months. The radius from each sheep was cut into the anatomical sectors: cranial, caudal, craniolateral, craniomedial, caudomedial, and caudolateral. Each anatomical sector was turned into a microradiograph for analysis. Densitometry was performed to determine the density of each specimen using the estimated thickness of aluminum (ETA) as the key. Statistical analysis assessed the resulting data to understand the effects of treatment, season of sacrifice, season of surgery, and anatomical sector by comparing both mean ETA and standard deviation ETA to understand changes in bone density. The results revealed significant differences between the ovariectomy and sham groups as well as variation within season of surgery and season of sacrifice in both groups. Anatomical sector showed no significant variation. The differences in the thickness of aluminum seen in the sheep that underwent a sham operation can be attributed to the presence of estrogen. The sheep that underwent an ovariectomy showed differences in the estimated thickness of aluminum that can be attributed to other seasonal characteristics including the influence of Vitamin D. The results and conclusions within this study can be used to influence bone material characteristics and bone loss test protocols in future osteoporosis and estrogen depletion studies.

PURPOSE: To understand the influences of mechanical loading on bone adaptation, the ground reaction force (GRF) applied to the bone must be quantified. The use of force plates in a lab setting is the accepted method for quantifying GRFs; however, this is not feasible in free-living situations. Recent developments in accelerometer technology may provide the ability to evaluate the effects of mechanical loading on bone outside of laboratory settings. The purpose of this project was to validate an accelerometer for the measurement of mechanical loading by comparing its output against GRFs. METHODS: Male and female participants (n = 20 males, 20 females; 18 to 49 yr) completed 10 repetitions of 9 common everyday movements (stand, walk, jog, run, 15 cm jump, step down from curb, drop down from curb, forward hop, and side hop) on a force plate with an accelerometer worn on their right hip. Then, a subset (n = 5 males, 5 females) wore an accelerometer on their right hip and played basketball, volleyball, and dodgeball as a group. Finally, all 40 participants wore an accelerometer home for 7 days. All activities were organized into derived activity categories labeled as low-, moderate-, and high-mechanical-load-intensity and used with 59 possible accelerometer variables to predict mechanical load. Models were fit using the randomForest package in R. Model performance (coefficient of determination [R2] and median absolute error) was evaluated using cross-validation. RESULTS: The percentage of variation mechanical load intensity explained by the models ranged from 0.27 to 0.78 with median absolute errors ranging from 0.20 to 0.49. The model with R2 = 0.78 contained the known activity categories and the accelerometer variables, but this is not realistic for free-living situations where activity categories will not be known. The two free-living models with the highest R2 values included derived activity categories and accelerometer variables, and estimated, on average, 21.1 and 20.7 hours per day in low-intensity, 1.6 and 1.7 hours per day in moderate-intensity, and 0.0 and 0.5 hours per day in high-intensity osteogenic activity, respectively. CONCLUSION: It is assumed that higher intensity activities (i.e., jumping vs. jogging) result in higher GRF values, but depending on the actual execution of the movement, this is not always the case. This research demonstrated that models containing the accelerometer variables performed better in predicting GRF than those containing only the derived activity categories. This supports the hypothesis that accelerometers provide valuable objective information when evaluating mechanical loading on bone.

Exercise is known to have a long-term benefit on bone mass in children, but little is known about the underlying mechanisms. The purpose of this investigation was to determine the acute effect of exercise on bone metabolism in pre-pubertal children. Biochemical markers of bone formation were measured in 4 male and 4 female children, 8 to 11 years of age. Each subject performed 50 vertical jumps. Serum osteocalcin and C-telopeptide of type I collagen (CTx), were determined prior to exercise and at 24 and 72 hours post exercise as indicators of bone formation and bone resorption. Osteocalcin concentration was 8.20 ± 3.65 ng•mL"' before exercise, and was 7.1 ± 3.7 ng•mL-' and7.4 ± 3.7 ng•mL-' at 24 hours and 72 hours post exercise, respectively (P > 0.05). CTx concentrations were 11632 ± 4093 pmol•L-' before exercise, and was 9831 ± 3159 pmol•L-' at 24 hours and 9722 ± 2426 pmol•L7' at 72 hours post exercise (P > 0.05). In conclusion an acute bout of ballistic exercise appears to have no effect on bone metabolism in pre-pubertal children. / School of Physical Education

The osteoclasts, the bone cells responsible for bone degradation, have a crucial role in the age-related bone loss and post-menopause osteoporosis. Rac1 and Rac2, members of the Rho-family of small GTPases, are known for having a key role in osteoclast formation and activity, which could be translated to bone quality. In this study, we characterize the roles of Rac1 and Rac2 on bone quality using an aged and osteoporotic mouse model. Bones from wild type, Rac1KO and Rac2KO mice were harvested for mechanical tests, bone densitometry, micro-computed tomography and histomorphometric analyses to evaluate bone mineralization and architecture. We observed that the deletion of Rac1 or Rac2 in pre-osteoclasts minimized bone loss in both age-related and post-menopause osteoporosis. These results highlight the importance of the two small GTPases in bone remodeling and identify Rac1 and Rac2 as potential targets for the development of new therapies for the treatment of osteoporosis.

The osteoclasts, the bone cells responsible for bone degradation, have a crucial role in the age-related bone loss and post-menopause osteoporosis. Rac1 and Rac2, members of the Rho-family of small GTPases, are known for having a key role in osteoclast formation and activity, which could be translated to bone quality. In this study, we characterize the roles of Rac1 and Rac2 on bone quality using an aged and osteoporotic mouse model. Bones from wild type, Rac1KO and Rac2KO mice were harvested for mechanical tests, bone densitometry, micro-computed tomography and histomorphometric analyses to evaluate bone mineralization and architecture. We observed that the deletion of Rac1 or Rac2 in pre-osteoclasts minimized bone loss in both age-related and post-menopause osteoporosis. These results highlight the importance of the two small GTPases in bone remodeling and identify Rac1 and Rac2 as potential targets for the development of new therapies for the treatment of osteoporosis.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on October 16, 2007) Vita. Includes bibliographical references.

L’os subit perpétuellement des contraintes mécaniques et physiologiques, ainsi sa qualité et sa résistance à lafracture évoluent constamment au cours du temps à travers le processus de remodelage osseux. Cependant,certaines pathologies osseuses comme l’ostéoporose ou la maladie de Paget altèrent cette dernière et conduisent àune augmentation du risque de fracture osseuse. La qualité osseuse est non seulement définie par la densitéminérale osseuse (DMO) mais également par les propriétés mécaniques ainsi que la microarchitecture. Au total, onévalue en France à environ 3 millions le nombre de femmes et 1 million le nombre d’hommes souffrantd’ostéoporose, pour un coût estimé à 1 milliard d’euros. La prévention par le développement d’outils de diagnosticest nécessaire. Le diagnostic doit permettre d’estimer la qualité osseuse (propriétés mécaniques, activitéscellulaires, architecture). Ces travaux de thèse proposent un modèle innovant permettant de combiner lesdifférents facteurs agissant sur le remodelage osseux, à savoir : (i) le comportement mécanique, (ii) l’activitécellulaire, (iii) le processus de transduction ; visant à traiter les différentes informations d’origines mécanique etbiochimique. Les lois de comportement mécaniques et cellulaires sont issues de modèles validés dans la littératureet la stratégie d’unification voit sa justification à travers différents travaux sur les mécanismes de transduction.Ainsi, l’implémentation de ces trois acteurs du remodelage dans une analyse par éléments finis permet d’obtenirun modèle mécano-biologique du remodelage de l’os trabéculaire. Le modèle est applicable à différentes échelles etpermet d’étudier le niveau de remodelage local modulé par l’activité physique et la concentration de certains agentsbiochimiques. L’application du modèle sur un volume virtuel de fémur selon différents scénarios cliniques donnedes résultats conformes aux observations faites en imagerie médicale. / By continuously undergoing mechanical and physiological stresses, bone quality and bone strength evolve throughremodeling process. However, osteoporosis and Paget’s disease for instance alter bone quality and increase the risk of bone fracture. Bone quality is mainly defined by its Bone Mineral Density (BMD) but mechanical properties and microarchitecture have also to be taken into account for a proper definition. About 3 million of women and 1 million of men suffer from osteoporosis which costs approximately 1 billion Euros per year in France. This highlights the necessity to develop diagnostic tools in order to enable proper bone quality characterization (mechanical properties, cellular activity and architecture).This thesis proposes an original model combining the main bone remodeling constituents which are : (i) the mechanical behavior, (ii) the cellular activity, (iii) the transduction phase ; enabling mechanical and biochemical information processing. Mechanical and cellular behavior models are taken from already published work and the transduction phase model unifying mechanical and biological information is inspired from the literature. Consequently, the implementation of these three main bone remodeling constituents into a finite element analysis gives a plausible mechano-biological model of trabecular bone remodeling. The developed model can be used at different scales in order to study the local amount of bone remodeled, magnified by physical activity and the concentration of some biochemical agents. Its application on virtual volume of femora under different clinical scenarios gives good results in respect to medical images observations.