Submitted by Luis Guilherme Macena (guilhermelg2004@gmail.com) on 2013-07-05T16:38:41Z No. of bitstreams: 1 Adriana de Mattos V. da Costa.pdf: 853931 bytes, checksum: 36bdda2da67d8874ebb33327c81a0c23 (MD5) / Made available in DSpace on 2013-07-05T16:38:41Z (GMT). No. of bitstreams: 1 Adriana de Mattos V. da Costa.pdf: 853931 bytes, checksum: 36bdda2da67d8874ebb33327c81a0c23 (MD5) Previous issue date: 2012 / Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil / Introdução: O aumento na ocorrência de fraturas secundárias à fragilidade óssea representa um significativo problema de Saúde Pública, já que corresponde a um importante aumento na morbidade, mortalidade e nos custos de mulheres na pós menopausa. Objetivos: Avaliar os fatores relacionados à ocorrência de fraturas em mulheres pós-menopausa acompanhadas em uma unidade básica de saúde. Metodologia: Foi realizado um estudo de coorte prospectivo, na ilha de Paquetá/RJ no ano de 2011. Através do banco de dados já existente, as mulheres foram localizadas por telefonemas e comparecimento no hospital local. As pacientes selecionadas foram submetidas a um questionário estruturado de avaliação de fatores relacionados à fragilidade óssea. Resultados: A incidência de fratura por fragilidade óssea encontrada foi de 21%, tendo como sitio principal o antebraço com 13%. A idade média da população foi de 72 anos com DP ± 9,0. No grupo de pacientes fraturadas 50% tinham entre 65 e 79 anos sugerindo ser essa faixa etária mais susceptível as fraturas por fragilidade óssea. Das pacientes que tiveram a Ultrassonometria óssea de calcâneo alterado, 22 % tiveram fraturas nesse período. Foi calculado o RR= 1,13 (IC95%: 0,48 - 2,63). As pacientes que tiveram fraturas se mostraram com maior sobrepeso ou obesas (72,2%), com maior historia familiar de fratura de quadril (13,3%) e com maior diagnostico de osteoporose (47,1%) do que as pacientes sem fraturas (p valor>0,05). E 23,5% das pacientes acamadas por mais de dois meses sofreram alguma fratura, com p valor <0,05. Na correlação entre as variáveis idade, tempo de menopausa e IMC, foi evidenciada uma associação positiva entre a idade e o tempo de menopausa nos grupos de pacientes com e sem fraturas. Conclusão: Os fatores de risco para fraturas por fragilidade óssea encontrados ajudam a conhecermos o perfil da nossa população e termos subsídios para combater esse agravo. / Introduction: The increased occurrence of secondary fractures associated with bone fragility represents a significant Public Health problem since it leads to a considerable increase in morbidity, mortality and in health care costs for postmenopausal women. Objectives: To evaluate the factors related to the occurrence of fractures in postmenopausal women attended at a public health center. Methodology: A prospective cohort study was conducted in Paquetá Island, Rio de Janeiro, in 2011. Using an existing database, these women were identified, contacted by phone and asked to come to the local hospital. The selected patients were submitted to a structured questionnaire assessing factors related to bone fragility. Results: The incidence of fracture due to bone fragility was of 21%, and the main site was the forearm, accounting for 13%. The average age of the population was 72 with a SD ± 9.0. In the group of fractured patients, 50% were between 65 and 79 years old, which suggest this is the age group that is most susceptible to fractures associated with bone fragility. Twenty two percent of the patients who had an altered quantitative ultrasonometry of the calcaneus had fractures in that period of their lives. The RR was calculated: RR = 1.13 (CI 95%: 0.48 – 2.63). The patients who had fractures were more overweight or obese (72.2%), had a longer family history of hip fracture (13.3%) and more diagnoses of osteoporosis (47.1%) than patients without fractures (p-value > 0.05). And 23.5% of the patients who were bedridden for more than two months suffered some type of fracture, with a p-value < 0.05. In the correlation between the different ages, time of menopause and BMI, a positive association between age and time of menopause became clear in the groups of patients with and without fractures. Conclusion: The risk factors for fractures associated with bone fragility help us to define the profile of our population and provide us with means to fight this problem.

Made available in DSpace on 2015-03-26T13:02:53Z (GMT). No. of bitstreams: 1 texto completo.pdf: 413656 bytes, checksum: 5228d2aaeb23b9cce2cae77c6ba8479e (MD5) Previous issue date: 2009-05-15 / During the absence of load on the skeleton, and even short periods of reduced physical activity, may arise bone weakening. Thus, common medical treatments for diseases muscle-equeléticas involving immobilization through temporary splints, traction or rest forced the risk of fractures increase. Physical activity is studied, both to prevent damage and to promote recovery of bone structure. Therefore, the objective of this research was evaluated by bone densitometry and mechanical testing, the influence of hypocinesia and subsequent activity on a treadmill or free movement in femurs of rats. Sixty-four Wistar rats were used. The animals were created until the age of sixty-five days for the beginning of the procedures experimental. They were divided into eight groups, being three control and five experimental. The animals in group 6 (G6), were created until completeting 93 days of age and served as a control for G1, which was to suspend the animal by the tail for 28 days. In G7, the animals were created until 121 days and were for the control groups, G2 (suspended and trained on a treadmill for 4 weeks) and G4 (suspended and released for 4 weeks. Already in the G8, the animals were created until 149 days and were for the control groups, G3 (suspended and trained on a treadmill for 8 weeks) and G5 (suspended and released for 8 weeks). We analyzed the content and bone mineral density of the left femur by bone densitometry. Another analysis related to mechanical properties of the middle third of the femur (maximum force necessary to break and stiffness). The suspension by the tail caused a decrease in bone mineral density, maximum strength and rigidity of the femur of animals. The training on a treadmill and free activity after suspension promoted the recovery of bone mineral content, density, increased bone stiffness and strength required to produce fracture in a similar way and over time. / Durante a ausência de carga no esqueleto, e mesmo em curtos períodos de atividade física diminuída, pode ocorrer enfraquecimento ósseo. Assim, tratamentos médicos comuns para doenças músculo-equeléticas que envolvam imobilização temporária por meio de talas, repouso forçado ou tração aumentam o risco de fraturas. A atividade física é a medida mais estudada, tanto para evitar danos quanto para promover recuperação da estrutura óssea. Portanto, o objetivo deste estudo foi avaliar, por meio da densitometria óssea e do ensaio mecânico, a influência da hipocinesia e posterior atividade de corrida em esteira ou movimentação livre na caixa em fêmur de ratos. Foram utilizados sessenta e quatro ratos Wistar com sessenta e cinco dias de idade e massa corporal média de 316,11 gramas. Eles foram separados aleatoriamente em oito grupos, sendo três controles e cinco experimentais. Os animais do grupo 6 (G6), foram criados até completarem 93 dias de idade e serviram de controle para G1, composto por ratos suspensos pela cauda por 28 dias. No G7, os animais foram criados até 121 dias e foram controle para os grupos, G2 (suspenso e treinado em esteira por 4 semanas) e G4 (suspenso e liberado por 4 semanas). No G8, os animais foram criados até 149 dias e foram controle para os grupos, G3 (suspenso e treinado em esteira por 8 semanas) e G5 (suspenso e liberado por 8 semanas). Foram analisados o conteúdo e a densidade mineral óssea do fêmur esquerdo por meio de densitometria óssea. Foram analisadas as propriedades mecânicas do terço médio do fêmur (força máxima de ruptura e rigidez). A suspensão pela cauda provocou a diminuição na densidade mineral óssea, na força máxima admitida e na rigidez do fêmur dos animais. O treinamento em esteira e a atividade livre na caixa após a suspensão promoveram recuperação do conteúdo mineral ósseo e da densidade mineral óssea e aumentou a rigidez óssea e a força necessária para produzir fratura de forma semelhante e ao longo do tempo.

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Purpose of Review: The incidence of diabetes is increasing worldwide. Diabetes mellitus is characterized by hyperglycemia, which in the long-term damages the function of many organs including the eyes, the vasculature, the nervous system, and the kidneys, thereby imposing an important cause of morbidity for affected individuals. More recently, increased bone fragility was also noted in patients with diabetes. While patients with type 1 diabetes mellitus (T1DM) have low bone mass and a 6-fold risk for hip fractures, patients with type 2 diabetes mellitus (T2DM) have an increased bone mass, yet still display a 2-fold elevated risk for hip fractures. Although the underlying mechanisms are just beginning to be unraveled, it is clear that diagnostic tools are lacking to identify patients at risk for fracture, especially in the case of T2DM, in which classical tools to diagnose osteoporosis such as dual X-ray absorptiometry have limitations. Thus, new biomarkers are urgently needed to help identify patients with diabetes who are at risk to fracture. - Recent Findings: Previously, microRNAs have received great attention not only for being involved in the pathogenesis of various chronic diseases, including osteoporosis, but also for their value as biomarkers. - Summary: Here, we summarize the current knowledge on microRNAs and their role in diabetic bone disease and highlight recent studies on miRNAs as biomarkers to predict bone fragility in T1DM and T2DM. Finally, we discuss future directions and challenges for their use as prognostic markers.

Osteogenesis imperfecta, innate brittle bone disease, is a very serious disease. It is inheritable disease of connective tissue, which shows by abnormal fragility of bones. The occurrence of this disease is one case in 10 000 30 000 births. The theoretical part of the thesis deals with the disease itself, also the psychical impact on children suffering from Osteogenesis imperfecta and the impact on their families as well. At the beginning of the research, three goals of this thesis were set: map out (on the basis of theoretical and practical backgrounds) the pitfalls of life of children with the disease Osteogenesis imperfecta, find out what are the most common difficulties by children with the disease Osteogenesis imperfecta and also find out the experiences of nurses with the care for children with disease Osteogenesis imperfecta. The empirical part of the thesis was processed by means of qualitative research conducted by the technique of semi-structured interview and narrative biographical interview. The research set were nurses working at the child departments in hospitals, parents of ill children and also an adult woman with the diagnosis of Osteogenesis imperfecta and two doctors. From the research emerged that among the most common difficulties of children is pain, which decreases the quality of their life. Small children can't engage in typical activities of children, such as going to a playground, older children can't attend for example music festivals. Children feel fear from fractures and are therefore limited in sports. Because of injuries and their treatments, the children have more absences at schools and therefore are isolated from peers. Nevertheless, the children with this disease can live a happy life. From the results of the research also emerges, that nurses working at the child departments of the hospitals attended by children with this illness have a good experiences with their treatment. They are able to give parents important information and know the specifics of application of the treatment. The results of the diploma thesis were presented at a national student conference and will be further published.

Der Typ-2-Diabetes mellitus (T2DM) wird mit einem erhöhten Frakturrisiko in Verbindung gebracht, welches auf krankheitsspezifische Defizite in der Knochenmikrostruktur und -qualität zurückzuführen ist. Da die zugrundeliegenden Mechanismen unzureichend verstanden sind, kommen präklinische Modelle, welche die diabetische Knochenerkrankung nachbilden, zur Erforschung der Pathogenese zum Einsatz. Die TallyHo/JngJ (TH)-Maus ist ein polygenes Modell für spontan auftretenden T2DM und Adipositas, welches den T2DM im Jugendalter beim Menschen rekapituliert. Aufgrund der unvollständigen Penetranz des Phänotyps entwickeln ~25 % der männlichen TH-Mäuse nie eine Hyperglykämie und können somit als nicht-diabetische Kontrolltiere mit identischen genetischen Background verwendet werden. Im Rahmen dieser Arbeit verwendeten wir männliche diabetische TH-Mäuse im Alter von zwölf Wochen für eine umfassende Charakterisierung des metabolischen und skelettalen Phänotyps und verglichen sie entweder mit altersgleichen nicht-diabetischen TH-Kontrollen oder mit den empfohlenen SWR/J-Kontrollen. Männliche TH-Mäuse mit T2DM zeigten eine Hyperglykämie und ein höheres Gewicht zusammen mit einer gestörten Glukosetoleranz und Insulinresistenz im Vergleich zu SWR/J und nicht-diabetischen TH-Kontrollen. Anhand der Mikro-Computertomographie (μCT) konnten festgestellt werden, dass TH-Mäuse mit T2DM ein erhöhtes kortikales Knochenvolumen und eine gesteigerte kortikale Knochendicke am Femur aufwiesen, während sie im Vergleich zu den SWR/J-Kontrollen einen trabekulären Knochenverlust sowohl im Femur als auch im Wirbelkörper zeigten. Trotz des trabekulären Knochenverlusts bei TH-Mäusen konnten wir keine Unterschiede im Bezug zum Knochenumbau feststellen, welcher anhand von Histomorphometrie und Serummarker zwischen diabetischen und nicht-diabetischen TH-Mäusen bestimmt wurde. Im Vergleich zu den SWR/J-Mäusen waren die Serum-Konzentrationen von Knochenumbaumarker P1NP und TRAcP5b bei TH-Mäusen niedriger, was darauf hindeutet, dass der SWR/J-Stamm per se einen höheren Knochenumsatz aufweisen könnte. Die biomechanischen Eigenschaften wurden mit einem 3-Punkt-Biegetest am Femur und einem Kompressionstest an der Wirbelsäule (L4) geprüft. Während es keine Unterschiede in der Knochenstärke des Femurs zwischen allen drei Gruppen gab, zeigte der Kompressionstest, dass der L4-Wirbelkörper von SWR/J-Mäusen im Vergleich zu den beiden Untergruppen der TH-Mäuse stärker waren. Im Rahmen der Osteozytencharakterisierung wurde eine niedrigere Anzahl von Osteozyten und ihren Dendriten bei TH-Mäusen mit T2DM durch Silbernitratfärbung im trabekulären Knochen des Femurs festgestellt. Die dreidimensionale Auswertung des ultrahochauflösenden μCT zeigte ein höheres Lakunenvolumen und eine höhere Lakunendichte bei SWR/J-Tieren im Vergleich zu beiden TH-Untergruppen im trabekulären und kortikalen Knochen des Femurs und des Wirbelkörpers. Weiterhin wurden Veränderungen in der Morphologie der Lakunen beobachtet wurden, wobei die Osteozyten bei TH-Mäusen mit T2DM im Vergleich zu SWR/J weniger kugelförmig, dafür aber gestreckter waren, was darauf hindeutet, dass die Form der Osteozyten ein Kompensationsmechanismus für die geringe Knochenmasse sein könnte. Eine hochkalorische Ernährung ist die Hauptursache für das Fortschreiten von Adipositas und T2DM. Daher ist eine diätetische Intervention, wie z. B. eine Kalorienrestriktion und eine Änderung der Ernährungszusammensetzung, ein wichtiger Behandlungsansatz zur Verbesserung der T2DM-Symptomatik. Es konnte gezeigt werden, dass eine ballaststoffreiche Ernährung die Hyperglykämie verbessert, die Hyperinsulinämie abschwächt und Entzündungen im Zusammenhang mit T2DM reduziert. Der Einfluss einer ballaststoffreiche Ernährung auf die Knochengesundheit im T2DM Kontext wurde jedoch bislang nicht erforscht. In unserer Studie verwendeten wir TH-Mäuse mit T2DM, die entweder mit einer Kontrolldiät oder einer ballaststoffreichen Diät gefüttert wurden. Wir konnten bestätigen, dass eine ballaststoffreiche Ernährung die T2DM-Symptome bei diabetischen TH-Mäusen verbessert. Während die ballaststoffreiche Ernährung keinen Effekt auf die kortikale oder trabekuläre Knochenstruktur im Femur bei diabetischen TH-Mäusen hatte, konnten wir eine geringere trabekuläre Knochenmasse in den Wirbelkörpern beobachteten. Eine ballaststoffreiche Ernährung hatte in beiden Gruppen keinen Einfluss auf die biomechanischen Eigenschaften von Oberschenkel- und Wirbelknochen. Anhand histomorphometrischer Analysen konnten wir eine Tendenz zur verstärkten Knochenformation nachweisen, jedoch war die Expression von Genen, die mit der Knochenbildung und dem WNT-Signalweg zusammenhängen, nicht verändert. Zusammenfassend zeigt diese Doktorarbeit die wesentlichen Charakteristika und potenziellen Einschränkungen der TALLYHO/JngJ- und SWR/J-Mausmodelle bei der Untersuchung von T2DM und dessen Auswirkungen auf die Knochengesundheit auf. Da sich die Knochenmikroarchitektur zwischen diabetischen und nichtdiabetischen TH-Mäusen nicht unterschied, ist diese Mauslinie kein ideales Modell zur Untersuchung diabetischer Knochenerkrankungen. Dennoch verbesserte eine ballaststoffreiche Ernährung den T2DM an sich, was bestätigt, dass TALLYHO/JngJ-Mäuse ein geeignetes präklinisches Modell sind, um die dem T2DM zugrundeliegenden Mechanismen abseits des Knochengewebes zu untersuchen. Diese Ergebnisse verdeutlichen uns die Notwendigkeit der Erforschung weiterer repräsentativerer Tiermodelle, um unser Verständnis von T2DM-bedingten Knochenerkrankungen zu verbessern.