Os bisfosfonatos (BF) são amplamente utilizados no tratamento de doenças osteolíticas como metástases ósseas e osteoporose. A osteonecrose dos maxilares associada ao uso de BF (OMAB) é caracterizada pela presença de osso exposto ou que pode ser sondado através de uma fístula que persiste por mais de oito semanas em pacientes com história de terapia de BF e sem história de radioterapia na região de cabeça e pescoço e/ou sem doença metastática nos maxilares. A incidência de OMAB aumenta com a potência, duração do tratamento e dose de BF recebida. Até o presente momento, a fisiopatologia da OMAB não está clara, dificultando a prevenção e o tratamento. O objetivo deste estudo foi avaliar o efeito da administração de altas doses Ácido Zoledrônico (AZ) por período prolongado no osso esponjoso da mandíbula e da metáfise proximal do fêmur de ratos Wistar. Para relacionar as descobertas à fisiopatologia da OMAB, o regime de administração de BF de um modelo animal relevante desta lesão foi reproduzido. Seis animais receberam AZ (0,6 mg / kg) e seis receberam solução salina no mesmo volume (Controles). Os compostos foram administrados por via intraperitoneal em cinco doses a cada 28 dias. A eutanásia dos animais ocorreu após 150 dias de início da terapia. As hemimandíbulas e fêmures direitos foram escaneados usando Micro-tomografia computadorizada (Micro-CT) de alta resolução (14 m). Para a primeira análise realizada neste estudo, os dados morfométricos do osso esponjoso foram calculados na região do segundo e primeiro molar na mandíbula e na metáfise do fêmur usando CTAnalyzer (Bruker, Bélgica). Para a segunda análise, cinco amostras de hemimandíbulas de cada grupo foram cortadas em lâminas histológicas (5 m) e coradas com Hematoxilina e Eosina. Para comparar os parâmetros morfométricos na Micro-CT e histologia, as imagens de Micro-CT foram espacialmente alinhadas à histologia. Os dados morfométricos do osso alveolar foram calculados usando o software CTAnalyzer (Bruker, Bélgica) na região entre as raízes mesial e distal do primeiro molar. A densidade da área vascular (área vascular/área total; VA/TA) e os dados histomorfométricos ósseos foram estimados usando Axiovision na mesma região (entre as raízes mesial e distal do primeiro molar). Foi adotada significância estatística de 5% ( = 0,05). Os animais tratados com AZ apresentaram aumento significativo na porcentagem de volume ósseo (p <0,05) com trabéculas mais espessas, osso mais compacto com menor separação trabecular na mandíbula e no fêmur. Na mandíbula, o aumento da densidade óssea e diminuição da separação trabecular foram fortemente correlacionados com a diminuição da área vascular observada no grupo AZ (p <0,05). Em conclusão, o tratamento de longa duração com altas doses de AZ foi significativamente associado ao aumento na densidade óssea e à diminuição dos espaços medulares, canais nutritivos e vasculatura do osso alveolar. A análise com Micro-CT revelou alterações semelhantes na estrutura óssea tanto na mandíbula quanto no fêmur do grupo AZ. / Bisphosphonates (BFs) are widely used in the treatment of osteolytic diseases such as bone metastases and osteoporosis. The osteonecrosis of the jaws related to BF (ONB) is characterized by the presence of exposed bone or bone that can be probed through a fistula that persists for more than eight weeks in patients with a history of BF therapy and without history of head and neck radiotherapy and / or without metastatic disease in the jaws. The incidence of ONB increases with potency, duration of treatment and dose of BF received. Thus far, the pathophysiology of ONB is unclear, hampering prevention and treatment. The aim of this study was to objectively assess the effect of long-term high-dose Zoledronic Acid (ZA) on cancellous bone in the jaw and femur of Wistar rats. In order to link our findings to the physiopathology of ONB, the therapeutic regiment of a relevant ONB animal model was reproduced. Twelve Wistar rats were randomly divided in two groups: six received Zoledronic acid (ZA; 0.6 mg / kg) and six (Controls) received saline solution in the same volume. The compounds were administrated intraperitoneally in five doses each 28 days. The rats were killed after 150 days of the therapy onset. Mandibles and femurs were scanned using a high-resolution (14m) micro-computerized tomography (Micro-CT). For the first analysis carried in this study, cancellous bone morphometric data were calculates in the region of the second and first molar in the mandible and in the proximal femur using CTAnalyzer (Bruker, Belgium). For the second analysis five samples were cut into histological slices (5m) and stained with Hematoxylin and Eosin. In order to compare the same morphological structures in Micro-CT and histology, the Micro-CT images were aligned to histology. Alveolar bone morphometric data (Micro-CT) was calculated using CTAnalyzer (Bruker, Belgium) in the region between the mesial and distal roots of the first molar. Blood vessels density and bone histomorphometric data were calculated using Axiovision (Carl Zeiss, Germany) in the same region used for Micro-CT evaluation. Statistical significance of 5% (=0.05) was adopted. ZA treated rats presented significant increase in the percentage of bone volume (p<0.05) with thicker trabeculae and more compact bone with smaller marrow spaces in the mandible and femur. In the mandible, the increase in bone density and decrease of marrow spaces size was strongly correlated with the decrease in the vascular area noticed in the ZA group (p<0.05). In conclusion, long-term high-dose ZA treatment was significant associated with the increase of bone density and the diminution of medullary spaces and nutritive canals size as well as decrease in vascularity of the alveolar bone. Micro-CT investigation showed similar changes in bone structure in the mandible and femur in the ZA group.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The aim of the first study was create an alternative method of surgical access to the atlantoaxial joint by ventral access without sternothyroid muscle section. A total of 15 dogs, weighing between eight and 12 kg were randomly divided in three groups according to postoperative period (PO), GI (30days), G II (60) and G III (90 days). The atlantoaxial joint was submitted to arthrodesis through the ventral access using Steinmann pins associated to acrylic resin. The access and exposure of the atlantoaxial joint without sternothyroid muscle section were completed without complications or additional limitations. None dog in this study had cough, dyspnea, regurgitation, laryngeal paralysis or Horner's syndrome. It can be concluded that the section of the sternothyroid muscle is an unnecessary procedure and does not interfere in the exposure of the atlantoaxial joint and in the arthrodesis of dogs through ventral access. The aim of the second study was test and compare the homogenous cancellous bone preserved in 98% glycerin in dogs submitted to atlantoaxial arthrodesis. Twelve dogs, weighing between 8 and 12 kg were randomly divided into three groups. Group I (GI): performed only the removal of joint cartilage and joint immobilization with acrylic resin and pins. Group II (GII): after removal of joint cartilage and immobilization, was performed the modeling and the placement of the homogenous cancellous bone at the determined location. The volume of homograft placed in the joint was measured using a precision balance and all animals received the same quantity. Group III (GIII): was performed the same procedure of the GI, however, was used autogenous cancellous bone graft at the determined location. Radiographic examinations were performed on all animals at 30, 60 and 90 days postoperatively. At 90 days of PO was carried out the 9 euthanasia of the animals to perform manual palpation test and CT and histological evaluation. For statistical analysis of the association between the degree of joint fusion, assessed by manual palpation, digitized radiographic images and CT scans and treatment groups, we applied the Chisquare test of independence. The test results were evaluated by the exact significance and considered statistically significant at 5% significance (p <0.05). By manual palpation test and by the CT images can be seen that there was no statistically significant difference between groups at 90 days postoperatively. Radiographic analysis of the atlantoaxial joint showed that the degree of fusion was similar among treatments, without statistical difference at 30, 60 and 90 days postoperatively. In relation to histopathology study at 90 days postoperatively, was found that bone formation in group I had 25% of each intensity (absent, mild, moderate, severe), in group II 75% mild and 25% severe, and in group III, 25% moderate and 75% severe. It can be concluded that the use of graft homogenous preserved in 98% glycerin in dogs undergoing atlantoaxial fusion method is a viable alternative for treatment of atlantoaxial instability. It can be also conclude that there is no difference in the degree of fusion was performed only removal of joint cartilage, suggesting this may be an alternative treatment of atlantoaxial instability. / Esta tese foi realizada em duas etapas distintas, sendo a primeira destinada à criação de um método alternativo de acesso cirúrgico a articulação atlantoaxial. O objetivo foi apresentar uma variação na técnica de acesso ventral à articulação para tratamento da instabilidade atlantoaxial sem a secção do músculo esternotireóideo. Foram utilizados 15 cães, pesando entre 8 e 12 kg, distribuídos aleatoriamente em três grupos iguais de acordo com o período pósoperatório (PO) denominados de I (30dias), II (60 dias) e III (90 dias). A articulação atlantoaxial foi submetida à artrodese por meio do acesso ventral utilizando pinos de Steinmann associados à resina acrílica autopolimerizável. O acesso e a exposição da articulação atlantoaxial sem a secção do músculo esternotireóideo foram realizados sem complicações ou limitações adicionais. Nenhum cão desta pesquisa apresentou complicação decorrente da intervenção. Pode-se concluir que a secção do músculo esternotireóideo é um procedimento desnecessário e que não interfere na exposição da articulação atlantoaxial e na realização da artrodese em cães por meio do acesso ventral. Na segunda etapa foi utilizado o homoenxerto de osso esponjoso conservado em glicerina a 98% em cães submetidos à artrodese atlantoaxial. O objetivo desta pesquisa foi testar e comparar o implante homógeno com o enxerto autógeno e com a realização da remoção da cartilagem articular isoladamente. Foram utilizados 12 cães, pesando entre 8 e 12 kg, distribuídos aleatoriamente em três grupos iguais. Grupo I (GI): realizada apenas a remoção da cartilagem articular e imobilização articular com pinos e resina acrílica. Grupo II (GII): Após remoção da cartilagem articular e imobilização da articulação, foi realizada a colocação e modelagem do enxerto ósseo esponjoso homógeno no local determinado. O volume de homoenxerto colocado na 7 articulação foi determinado utilizando balança de precisão e todos os animais receberam a mesma quantidade. Grupo III (GIII): Foi realizado o mesmo procedimento do GII, no entanto, foi utilizado enxerto ósseo esponjoso autógeno no local determinado. Exames radiográficos foram realizados em todos os animais aos 30, 60 e 90 dias de PO. Aos 90 dias de PO foi realizada a eutanásia dos animais para realização de testes de palpação manual, avaliação tomográfica e histológica. Para análise estatística da associação entre o grau de fusão articular, avaliado por palpação manual, das imagens radiográficas digitalizadas e tomográficas e os grupos de tratamento, aplicou-se o Teste Qui-quadrado de independência. Os resultados dos testes foram avaliados pela significância exata, e considerados estatisticamente significantes a 5% (p < 0,05). Pelo teste de palpação manual e pelas imagens tomográficas pode-se perceber que não houve diferença estatisticamente significativa entre os grupos aos 90 dias de PO. A análise radiográfica da articulação atlantoaxial mostrou que o grau de fusão foi semelhante entre os tratamentos, sem diferença estatística, aos 30, 60 e 90 dias de PO. Com relação ao estudo histopatológico aos 90 dias de PO foi verificado que a neoformação óssea no grupo I apresentou níveis de intensidade proporcional (ausente, leve, moderada, acentuada), no grupo II, 75% leve e 25% acentuada e no grupo III, 25% moderada e 75% acentuada. Pode-se concluir que a utilização de enxerto homógeno conservado em glicerina a 98% em cães submetidos à artrodese atlantoaxial é um método alternativo viável para tratamento de instabilidade atlantoaxial. Pode-se concluir também que não existe diferença quanto ao grau de fusão articular quando foi realizada apenas a remoção da cartilagem articular, sugerindo que essa possa ser mais uma alternativa ao tratamento da instabilidade atlantoaxial.

The aim of this master’s thesis is to determine the effective material properties of cancellous bone. In the first part of this work, finite element models are used for numerical homogenization of trabecular structures. It is shown that the applied boundary conditions have a strong influence on the effective material properties. To this end, different boundary condition are opposed and discused. In the second part, the Levenberg-Marquardt method is used to identify the preferred direction. Furthermore, it is shown that cancellous bone can be modelled as a transverse isotropic material. Finally, the homogenized continua are compared with the microstructural models of cancellous bone. / Ziel der Masterarbeit ist die Bestimmung der effektiven Materialparameter von spongiösem Knochen (lat. spongia „Schwamm“). Die numerische Homogenisierung von Trabekelstrukturen erfolgt mit Hilfe der Finite-Elemente-Methode. Es wird gezeigt, dass die verwendeten Randbedingungen einen starken Einfluss auf die effektiven Materialparameter ausüben. Die verschiedenen Randbedingungen werden dazu gegenübergestellt und diskutiert. Im zweiten Teil erfolgt mit Hilfe des Levenberg-Marquardt-Verfahrens die Identifizierung von ausgezeichneten Richtungen.Weiterhin wird gezeigt, dass die Spongiosa näherungsweise als transversalisotropes Material modelliert werden kann. Am Ende erfolgt der Vergleich des homogenen Ersatzkontinuums mit dem Mikrostrukturmodell der Spongiosa.

Introdução: A tomografia computadorizada periférica quantitativa de alta resolução (HR-pQCT) é um método diagnóstico que avalia microarquitetura óssea e estima resistência óssea por análise de elemento finito, facilitando a compreensão da fisiopatologia das fraturas. Objetivo: Avaliar associação de fraturas vertebrais moderadas e graves com parâmetros obtidos na HR-pQCT, escore trabecular ósseo (TBS) e densidade mineral óssea areal em idosos da comunidade. Métodos: Foram recrutados 276 idosos da coorte SPAH. Dados clínicos foram obtidos a partir de um questionário específico. A fratura vertebral (FV) foi avaliada por DXA-VFA utilizando-se o método semiquantitativo de Genant. HR-pQCT e DXA foram realizados no mesmo dia da coleta de sangue. O modelo de regressão logística foi realizado para verificar quais fatores foram associados de forma independente com a fratura vertebral moderada e grave. Resultados: Na tíbia, mulheres com FV moderada/grave apresentaram menor densidade mineral óssea volumétrica, menor número de trabéculas, menores valores dos parâmetros de resistência óssea e maior separação trabecular; e os homens apresentaram menor número de trabéculas, menor parâmetro de resistência óssea e maior separação trabecular. No rádio, as mulheres com FV moderada/grave tinham menor densidade mineral óssea volumétrica, espessura trabecular e cortical e menor valor do parâmetro de análise do elemento finito; e os homens tinham menor densidade mineral óssea volumétrica trabecular e menor valor de parâmetro de análise do elemento finito. Não foram observadas diferenças no TBS em ambos os sexos. A análise de regressão logística revelou que uma menor densidade mineral óssea volumétrica trabecular na tíbia em mulheres (OR: 0,980, 95% CI: 0,963-0,997, p = 0,022) e uma menor densidade mineral óssea areal do colo femoral e fêmur total em homens (OR: 0,002, IC 95%: 0-0,607, p = 0,033 e OR: 0,003, IC 95%: 0-0,623, p = 0,033) foram independentemente associados com FV moderada/grave. Conclusão: As imagens da HR-pQCT detectaram diferenças na microarquitetura óssea em mulheres idosas com FV moderada/grave independente de densidade mineral óssea areal e TBS por DXA; e HRpQCT pode ser uma ferramenta útil para avaliar o risco de fratura. Diferentemente, nos homens, a densidade mineral óssea areal do fêmur foi associada à FV moderada/grave; e a DXA continua sendo uma ferramenta importante para predizer a FV / Background: Many vertebral fractures (VF) occur in individuals classified by DXA as low risk for fragility fractures. Thus, the aim of this study was to verify the association between VF and peripheral bone microarchitecture and strength parameters using also high-resolution peripheral quantitative computed tomography (HR-pQCT) and axial bone microarchitecture by trabecular bone score (TBS). Study design: Cross-sectional study of 276 subjects aged >=65 years from SPAH cohort. Methods: Lateral scans of spine obtained from Vertebral Fracture Assessment by DXA were analyzed to assess VF. HR-pQCT was performed at radius and tibia. TBS was performed using DXA. Results: At tibia, women with Moderate/severe VF had lower volumetric bone density (vBMD), trabecular number (Tb.N), strength parameters and higher trabecular separation (Tb.Sp); and men had lower Tb.N, strength parameters and higher Tb.Sp. At radius, women with moderate/severe VF had lower v.BMD, trabecular and cortical thickness and strength parameters; and men had lower trabecular v.BMD and strength parameters. No differences were observed in TBS in both genders. Logistic regression analysis revealed that lower trabecular vBMD at tibia in women (OR: 0.980, 95%CI: 0.963-0.997, p = 0.022) and lower femoral neck aBMD and total hip in men (OR: 0.002, 95%CI: 0-0.607, p = 0.033 and OR: 0,003, IC 95%: 0-0,623, p = 0,033) were independently associated with VF. Conclusion: HR-pQCT images detected differences on bone microstructure in older women with moderate/severe VF independent of aBMD and TBS by DXA and HR-pQCT could be useful tool to assess fracture risk. Differently, in men femoral aBMD was associated with moderate/severe VF and DXA continue an important tool for predicting VF

Introdução: A tomografia computadorizada periférica quantitativa de alta resolução (HR-pQCT) é um método diagnóstico que avalia microarquitetura óssea e estima resistência óssea por análise de elemento finito, facilitando a compreensão da fisiopatologia das fraturas. Objetivo: Avaliar associação de fraturas vertebrais moderadas e graves com parâmetros obtidos na HR-pQCT, escore trabecular ósseo (TBS) e densidade mineral óssea areal em idosos da comunidade. Métodos: Foram recrutados 276 idosos da coorte SPAH. Dados clínicos foram obtidos a partir de um questionário específico. A fratura vertebral (FV) foi avaliada por DXA-VFA utilizando-se o método semiquantitativo de Genant. HR-pQCT e DXA foram realizados no mesmo dia da coleta de sangue. O modelo de regressão logística foi realizado para verificar quais fatores foram associados de forma independente com a fratura vertebral moderada e grave. Resultados: Na tíbia, mulheres com FV moderada/grave apresentaram menor densidade mineral óssea volumétrica, menor número de trabéculas, menores valores dos parâmetros de resistência óssea e maior separação trabecular; e os homens apresentaram menor número de trabéculas, menor parâmetro de resistência óssea e maior separação trabecular. No rádio, as mulheres com FV moderada/grave tinham menor densidade mineral óssea volumétrica, espessura trabecular e cortical e menor valor do parâmetro de análise do elemento finito; e os homens tinham menor densidade mineral óssea volumétrica trabecular e menor valor de parâmetro de análise do elemento finito. Não foram observadas diferenças no TBS em ambos os sexos. A análise de regressão logística revelou que uma menor densidade mineral óssea volumétrica trabecular na tíbia em mulheres (OR: 0,980, 95% CI: 0,963-0,997, p = 0,022) e uma menor densidade mineral óssea areal do colo femoral e fêmur total em homens (OR: 0,002, IC 95%: 0-0,607, p = 0,033 e OR: 0,003, IC 95%: 0-0,623, p = 0,033) foram independentemente associados com FV moderada/grave. Conclusão: As imagens da HR-pQCT detectaram diferenças na microarquitetura óssea em mulheres idosas com FV moderada/grave independente de densidade mineral óssea areal e TBS por DXA; e HRpQCT pode ser uma ferramenta útil para avaliar o risco de fratura. Diferentemente, nos homens, a densidade mineral óssea areal do fêmur foi associada à FV moderada/grave; e a DXA continua sendo uma ferramenta importante para predizer a FV / Background: Many vertebral fractures (VF) occur in individuals classified by DXA as low risk for fragility fractures. Thus, the aim of this study was to verify the association between VF and peripheral bone microarchitecture and strength parameters using also high-resolution peripheral quantitative computed tomography (HR-pQCT) and axial bone microarchitecture by trabecular bone score (TBS). Study design: Cross-sectional study of 276 subjects aged >=65 years from SPAH cohort. Methods: Lateral scans of spine obtained from Vertebral Fracture Assessment by DXA were analyzed to assess VF. HR-pQCT was performed at radius and tibia. TBS was performed using DXA. Results: At tibia, women with Moderate/severe VF had lower volumetric bone density (vBMD), trabecular number (Tb.N), strength parameters and higher trabecular separation (Tb.Sp); and men had lower Tb.N, strength parameters and higher Tb.Sp. At radius, women with moderate/severe VF had lower v.BMD, trabecular and cortical thickness and strength parameters; and men had lower trabecular v.BMD and strength parameters. No differences were observed in TBS in both genders. Logistic regression analysis revealed that lower trabecular vBMD at tibia in women (OR: 0.980, 95%CI: 0.963-0.997, p = 0.022) and lower femoral neck aBMD and total hip in men (OR: 0.002, 95%CI: 0-0.607, p = 0.033 and OR: 0,003, IC 95%: 0-0,623, p = 0,033) were independently associated with VF. Conclusion: HR-pQCT images detected differences on bone microstructure in older women with moderate/severe VF independent of aBMD and TBS by DXA and HR-pQCT could be useful tool to assess fracture risk. Differently, in men femoral aBMD was associated with moderate/severe VF and DXA continue an important tool for predicting VF

Les prothèses totales d’épaule ont une survie limitée due essentiellement au descellement de l’implant scapulaire. Le but de ce travail de recherche est la contribution à la mise au point d’un nouvel implant scapulaire à fixation sans ciment.Une première partie a concerné la caractérisation de l’anisotropie et des hétérogénéités de l’os spongieux de la glène par une expérimentation en compression, cette partie a abouti à l’élaboration d’une loi de comportement de l’os spongieux de la glène. La seconde partie de ce travail s’est focalisée sur la modélisation par éléments finis des contraintes aux points d’ancrage de l’implant.Les résultats des tests de simulation montrent l’incapacité du spongieux à assurer un effet press-fit dans le plan transversal, car on observe le dépassement des contraintes maximales pour un déplacement minime. Ce résultat met en question les modes de fixation primaire utilisés ce jour dans les prothèses sans ciment. Nos résultats montrent que la modification de la direction de chargement serait susceptible d’améliorer la fixation primaire ce qui ouvre des perspectives nouvelles pour le dessin d’une prothèse sans ciment. / Total shoulder prostheses have a limited survival due mainly to the loosening of the glenoid implant. The purpose of this research is the contribution to the development of a new glenoid implant with cementless fixation.The first part concerned the characterization of the anisotropy and heterogeneity of cancellous bone of the glenoid by a compression experimental tests, this part has led to the drafting of a law of behavior of cancellous bone of the glenoid . The second part of this work has focused on finite element modeling of stress around the anchors of the glenoid implant.Simulation test results show the inability of the transversal plane of the glenoid to ensure effective press-fit fixation with stresses above strength properties of the cancellous bone with a minimal displacement. This calls into question the current modes of primary fixation of cementless implant. However, it appears that a change in the direction of loading would be beneficial for the primary fixation, which opens new perspectives for the design of a cementless prosthesis.

Die vorliegende Arbeit beschäftigt sich mit der Frage, inwieweit die pränatale Knochenentwicklung von der Dexamethasongabe beeinflusst wird. Die Glukokortikoidtherapie ist weit verbreitet und ihre Nebenwirkungen sind hinreichend bekannt. Auch die Wirkung auf den Knochenstoffwechsel wurde intensiv erforscht, allerdings nicht in Bezug auf die pränatale Therapie. Die Verabreichung von Dexamethason zur Vorbeugung des Atemnotsyndroms betrieb man zeitweise sehr intensiv. Mit Zunahme der Forschung auf diesem Gebiet, stellten sich allerdings erhebliche Auswirkungen auf die prä- und postnatale Entwicklung der Kinder heraus. Deswegen ist der Einsatz zur RDS-Prophylaxe heute relativ zurückhaltend. Zu diesem Zweck wurden 30 männliche Nachkommen der Spezies Callithrix jacchus, deren Mütter während der Schwangerschaft zu unterschiedlichen Zeitpunkten eine Dexamethasonapplikation erhielten, untersucht. Es erfolgte eine Einteilung in drei Gruppen: frühe Applikation, späte Applikation und in die Kontrollgruppe. Während der ersten beiden Lebensjahre wurden Körpergröße und Körpergewicht in regelmäßigen Abständen dokumentiert. Im Alter von 2 Jahren wurden die Tiere euthanasiert. Als Untersuchungsobjekte dienten Oberschenkel- und Schienbein-knochen. Es wurden die Kortikalisdicke, die Flächenverhältnisse von Trabekeln, rotem Knochenmark und gelben Fettmark analysiert sowie die Knochendichte ermittelt. Die Ergebnisse zeigen eine deutlich reduzierte diaphysale Kortikalisdicke beider Knochen in der Gruppe mit früher Dexamethasonapplikation. In der späten Appli-kationsgruppe dagegen fand man eine stärker ausgeprägte Kortikalis diaphysal, aber eine reduzierte im metaphysalen Bereich. Diese Schwächung kann besonders im Alter Frakturen im Oberschenkelhals begünstigen, vor allem wenn eine hormonell bedingte Osteoporose als Begleiterkrankung hinzukommt. In beiden Versuchsgruppen kann eine deutliche Schwächung der Knochensubstanz im Bereich der Knie, in diesem Fall die Hauptbelastungszone der Tiere, bedingt durch den Vierfüßlergang, nachgewiesen werden. Der Oberschenkel reagiert auf die Dexamethasonapplikation am sensitivsten. Des Weiteren sind Veränderungen der Flächenverhältnissen aufgetreten. Bei der frühen Applikation von Dexamethason ist eine deutlich reduzierte Anzahl an rotem Knochenmark zu finden, während bei der späten Applikation eine vermehrte Anzahl nachweisbar ist. Dies zeigt, dass Dexamethason auch Auswirkungen auf die Blutbildung und das Immunsystem mit sich bringt. Die Ergebnisse dieser Arbeit sollten dazu anregen, weiter auf diesem Gebiet zu forschen, da die Anzahl an Publikationen noch limitiert ist. Bezüglich der RDS-Prophylaxe ist über eine strengere Indikationsstellung nachzudenken.

Top screw pullout is a significant problem in anterior scoliosis correction, with rates of 5-15% reported in the literature. The Mater Misericordiae Hospital in Brisbane currently has a series of 125 patients with scoliosis treated by thoracoscopic anterior fusion, instrumentation and correction between April 2000 and August 2007. In this series 11 top screws are known to have pulled out (a rate of 8.8%), with six occurring in the first week, and all within 6 weeks, suggesting that the problem is one of excessive static force rather than fatigue. This thesis describes a biomechanical investigation into the mechanics of vertebral body screw pullout in anterior scoliosis surgical constructs. Previous biomechanical studies of vertebral body screws have evaluated their resistance to either straight pullout or cephalo-caudad compression forces, however the aim of this study was to assess screw resistance to more realistic loading conditions, namely pullout of initially angled screws, and pullout where the motion path is an arc rather than a straight axial pullout, as would be expected in a single rod anterior construct. The first series of experiments involved straight and angled pullout tests using synthetic bone. In the angled tests, both locked and free-to-pivot configurations were tested. The second series of experiments tested the effect of cephalo-caudad pre-compression (the actual deformity correction step performed during surgery) on subsequent axial pullout strength. A third series of experiments performed arc pullouts using synthetic bone, and the final series of experiments tested the pullout resistance of a newly proposed screw position configuration against the standard screw positioning using ovine lumbar vertebrae. Synthetic bone testing revealed that for initially angled pullout, resistance is greatest as the screw angle approaches 0 (ie a direct axial pullout). Cephalo-caudad pre-compression reduced subsequent pullout strength for cases where a staple was not used under the screw head, but if a staple was used the pre-compression did not decrease pullout force significantly. Arc pullout resistance was greatest when the screw was angled at 10 cephalad, and the mean pullout strength for the proposed screw configuration using ovine lumbar vertebrae (1864N) was almost double that of the standard screw positioning (993N). The clinical implication of this study is that top screw pullout resistance can be maximised by placing the top screw as close as possible to the top endplate and the bottom screw as close as possible to the bottom endplate, although this will have detrimental effects on the pullout of the second screw should the top screw pull out. Screw angulation is a less important factor but any angulation should be in a cephalad direction and around 10º in magnitude. The experimental results also suggest that the use of a staple may play a role in preventing cephalo-caudad pre-compression forces from reducing screw resistance to subsequent pullout forces.

Trabecular bone forms the internal scaffolding of most bones, and consists of a microscopic lattice-like structure of interconnected bony struts. Experimental work has demonstrated that trabecular bone adapts its structural rigidity and orientation in response to the strains placed upon the skeleton during life, a concept popularly known as “Wolff’s Law” or “bone functional adaptation”. Anthropological work has focused on correlating variation in primate trabecular bone to locomotor and masticatory function, to provide a context for the interpretation of fossil morphology. However, intraspecies variation and its underlying mechanisms are still poorly understood. In this thesis, variation in trabecular bone structure is examined in the human foot in four archaeological populations. The aim is to tease apart the factors underlying variation in human trabecular microstructure to determine whether it may be a suitable proxy for inferring terrestrial mobility in past populations. μCT scanning is used to image the three-dimensional trabecular structure of the talus, calcaneus, and first metatarsal in samples from four archaeological populations. Trabecular structure is quantified in seventeen volumes of interest placed throughout the foot. Trabecular bone is influenced by a variety of factors including body mass, age, diet, temperature, genetics, sex, and mechanical loading. Before trabecular structure can be used to infer habitual behaviour, the effects of these factors need to be understood and ideally statistically accounted for. Therefore, the effects of variation in bone size and shape, body mass, age, and sex on human trabecular structure are examined in four populations. Significant effects of body mass and age are reported, but little sexual dimorphism was found within populations. Taking these results into account, variation in trabecular structure is compared between archaeological populations that were divided into high and low mobility categories. Results demonstrate that the four populations show similar patterns of trabecular variation throughout the foot, with a signal of terrestrial mobility level superimposed upon it. Terrestrial mobility is associated with greater bone volume fraction and thicker, more widely spaced, and less interconnected trabeculae. Ontogeny of trabecular bone in the human calcaneus is investigated in two archaeological populations in the final chapter of the thesis. Results indicate that calcaneal trabecular bone adapts predictably to changes in loading associated with phases of gait maturation and increases in body mass. This opens the possibility of using trabecular structure to serve as a proxy of neuromuscular development in juvenile hominins. This work demonstrates that trabecular bone may serve as a useful proxy of habitual behaviour in hominin fossils and past populations when all contributing factors are carefully considered and ideally statistically controlled for.

Afin de développer des moyens de protection et de prévention adaptés aux personnes et à leurs activités, ces travaux de thèse contribuent à la compréhension des mécanismes de rupture sous différentes vitesses de chargement. Le comportement de l’os spongieux bovins, non confiné, avec moelle, a été étudié sur 8 niveaux de vitesse de déformation, du régime quasi-statique (10-3/s) au régime dynamique (600/s). Pour cela, des techniques expérimentales de compression interrompue ont été développées. La caractérisation architecturale micro CT pré-compression a ensuite mis en évidence les paramètres de description architecturale pertinents ainsi que le rôle de cette organisation dans le comportement de l’os spongieux sous différents régimes de sollicitation. Associé à l’imagerie micro CT post compression, les faciès de rupture ont été observés. Malgré la base de données expérimentales (127 échantillons), toutes les configurations architecturales présentes chez un être vivant n’ont pas pu être testées. Un premier générateur d’architecture a alors été développé, permettant de créer numériquement des structures osseuses. S’affranchissant du caractère destructif des essais et la dépendance vis à vis des échantillons, cet outil contribue à la compréhension des mécanismes de fracture de l’os spongieux sur une grande plage de vitesses de déformations. Les fondations nécessaires à la validation d’un tel modèle en utilisant la méthode des éléments discrets s’inscrivent enfin comme perspectives immédiates de ces travaux. / In order to develop means of protection and prevention for people and their activities, this thesis manuscript contributes towards understanding failure mechanisms under different loading rates. The behavior of cancellous bovine bone, unconfined, with marrow, has been studied over a range of 8 strain rates, from quasi-static (10-3/s) to dynamic (600/s) regimes. For the latter, specific interrupted compression experimental techniques were developed. The pre-compression micro CT architectural characterization highlighted relevant architectural parameters and the role this organization may have in the behavior of cancellous bone under different regimes. The fracture surfaces of the specimen were observed by post compression micro CT imaging. Despite the large experimental data base (127 samples), all architectural configurations present in individuals could not be tested. A first architectural generator was then developed to digitally create bone structures. Whilst avoiding the destructive nature of the test and the dependence of the samples, this tool contributes to the understanding of the fracture mechanisms of cancellous bone over a large range of strain rates. Finally, the immediate prospects for this work include the validation of the architectural generator using the discrete element method.