Well know therapies for the treatment of osteoporosis, syndrome characterized by increased bone fragility and fracture consist primarily of drugs which prevent bone losses, such as bisphosphonates. Among them, alendronate (PO3)-(OH)-C-((CH2)3 NH3)-(PO3) is one of the chosen treatments in the clinic, IC50 = 50 nM. In this work a study of the molecular alendronate and three of its crystals (sodium alendronate trihydrate and anhydrous and calcium alendronate ) is performed in the scope of Density Functional Theory (DFT). In the first case, the focus is the lowest energy conformations of the molecular alendronate in vacuum, in an aqueous medium in accordance with the model of polarization continuum (PCM), and interacting with three molecules of water of a sodium atom based on the characteristics structural relevadas diffraction X-ray crystal alendrontao sodium trihydrate; their vibrational infrared and Raman spectra are calculated to explain in detail the abundant signatures of the phosphate group in the frequency range 400-1400 cm −1 with the assignments of the most important vibrational modes. In the case of crystals, their structural, electronic and optical properties are obtained in the generalized gradient approximation taking into account the description of the term correlation and exchange Tchatschenko (GGA+TS ); Hirshfeld population analysis in which verified is presented alendronate is that the three crystals is in zwitterionic state. From the calculation of the band structure was obtained GAPs with very close values for the three crystals, however, with the density of states and characteristic for each crystal. The effective masses, dielectric function and theoretical optical absorptions for all crystals are presented. / Terapias estabelecidas para o tratamento da osteosporose, sÃndrome caracterizada por aumento na fragilidade Ãssea e fraturas, consistem primariamente de drogas que previnem a perda Ãssea, como os bisfosfonatos. Entre eles, o alendronato (PO3)-(OH)-C-((CH2)3 NH3)-(PO3) à um dos tratamentos escolhidos na clÃnica, pois possui o IC50=50 nM. Neste trabalho à realizado um estudo do alendronato molecular e de trÃs de seus cristais (alendronato de sÃdio trihidratado e anidro, e alendronato de cÃlcio) utilizando da Teoria do Funcional da Densidade (DFT). No primeiro caso, o foco sÃo os confÃrmeros de menor energia do alendronato molecular no vÃcuo, em meio aquoso de acordo com o modelo contÃnuo polarizÃvel (PCM), e interagindo com trÃs molÃculas de Ãgua e um Ãtomo de sÃdio de acordo com as caracterÃsticas estruturais reveladas por difraÃÃo de raios-X do cristal do alendrontao de sÃdio trihidratado; seus espectros vibracionais no infravermelho e Raman sÃo calculados para explicar com detalhes as abundantes assinaturas do grupo fosfato no intervalo de frequÃncia 400-1400 cm−1, com as atribuiÃÃes dos modos vibracionais mais importantes. No caso dos cristais, sÃo obtidas suas propriedades estruturais, eletrÃnicas e Ãpticas na aproximaÃÃo da gradiente generalizado levando-se em conta a descriÃÃo do termo de correlaÃÃo e troca de Tchatschenko (GGA+TS); à apresentada a anÃlise populacional de Hirshfeld na qual verificou-se que o alendronato nos trÃs cristais encontra-se no estado zwitterionico. A partir do cÃlculo de estrutura de banda, foi obtido GAPs com valores muito prÃximos para os trÃs cristais, porÃm, com densidade de estados bem caracterÃstica para cada cristal. SÃo apresentadas as massas efetivas, funÃÃo dielÃtrica e absorÃÃes Ãpticas teÃricas para todos os cristais.

Orientador: Jaime Amaya-Farfan / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-10T13:16:03Z (GMT). No. of bitstreams: 1 Jackix_ElisadeAlmeida_M.pdf: 5040809 bytes, checksum: 9ccad63464c1464ceb7ded271d23cb5c (MD5) Previous issue date: 2008 / Resumo: A osteoporose constitui a enfermidade do esqueleto de maior incidência mundial e é caracterizada por redução da massa óssea levando ao aumento da susceptibilidade a fraturas. Nas mulheres, a osteoporose está associada à queda dos níveis de estrogênio, que acompanha a menopausa. O colágeno compreende cerca de 95% das proteínas dos ossos, e é parcialmente responsável pelas propriedades biomecânicas do osso. Os hidrolisados enzimáticos de colágeno (HC) são produtos obtidos a partir da hidrólise da gelatina e têm recebido atenção por suas propriedades no tratamento de doenças osteoarticulares. Objetivo: avaliar o efeito de um HC sobre características ósseas em modelo osteopênico com ratas. Métodos: 48 ratas adultas foram divididas em 6 grupos: 3 ovariectomizados, 1 sham-operated e 2 intactos, tratados com dieta AIN-93 M, suplementada com HC ou gelatina (controle), em dois níveis: (1) quantidade equivalente a 5X ao recomendado para humanos (10g/D), e outro (2) com nível 10X maior. Após 8 semanas, os ossos do fêmur e da coluna vertebral foram extirpados, e o sangue coletado; determinaram-se osteocalcina e fosfatase alcalina sérica, e no osso, determinou-se peso, teor protéico, conteúdo mineral (Ca, Na, Zn, Fe, K, P, Mg, Mn, Pb e Cu). Realizou-se também a análise de cortes histológicos dos diferentes grupos. Avaliou-se a resistência biomecânica por meio dos testes de flexão em três pontos nos fêmures e compressão nas vértebras. Resultados: As vértebras do grupo que recebeu a maior dosagem de HC suportaram uma carga 4X maior, e tiveram percentuais de proteína óssea e valores de osteocalcina maiores, do que aquelas que não tiveram suplementação ou receberam gelatina (p<0,05). A análise histológica mostrou maior espessura das trabéculas ósseas nos fêmures e vértebras das ratas que receberam HC. Conclusão: O HC contribuiu para uma maior conservação, composição e resistência óssea, quando comparado à gelatina / Abstract: Osteoporosis, the skeletal disease of highest incidence in the world is characterized by the reduction of bone mass and commonly leads to increased susceptibility of fractures. In women, osteoporosis is associated to the cessation of estrogen secretion and menopause. Collagen accounts for approximately 95% of the bone proteins and is to a large extent responsible for its biomechanical properties. Collagen hydrolyzates (CH) consist of mixtures of peptides obtained by a partial hydrolysis of gelatins, which have received considerable scientific attention as potential repositories of osteoraticular tissues. Objective: to evaluate the effect of supplementing the diets of ovariectomized rats with a commercial CH upon the compositional, biomechanical and histological characteristics of the bone. Methods: 48 adult female rats were divided into 6 groups: 3 of them ovariectomized, 1 sham-operated and 2 intact, fed the AIN 93-M diet, supplemented with either CH or gelatin (Control), in two levels: (1) a dose equivalent to 5x the amount suggested for humans (10g/D) and (2) a dose 10x greater. After eight weeks of treatment, the bones of femurs and vertebrae were excised the blood collected and serum osteocalcin and serum alkaline phosphatase determined. For the bone, gross weight, protein and mineral content (Ca, Na, Zn, Fe, K, P, Mg, Mn, Pb and Cu) were determined. Histological analysis of bone tissue sections was also performed to compare the different treatments. Biomechanical strength was assessed by means of 3-point flexion and compression tests of the femurs and vertebrae, respectively. Results: the vertebrae of the ovariectomized group that received the higher dosage of CH withstood a load 4x greater and exhibited higher levels of protein and osteocalcin content than those that received the gelatin or no supplementation at all. Histological analysis of the femurs and vertebrae of castrated rats that received the CH showed greater thickness than those receiving the gelatin supplementation. Conclusion: CH consumption as a diet supplement by the ovariectomized rat had an unequivocal contribution in the conservation or preservation of bone mass not seen when gelatin was used as a supplement / Mestrado / Nutrição Experimental e Aplicada à Tecnologia de Alimentos / Mestre em Alimentos e Nutrição

O presente estudo teve como objetivo verificar se a radiografia periapical é capaz de identificar pacientes com baixa massa óssea, combinando a análise morfológica do trabeculado ósseo e a densidade radiográfica a parâmetros clínicos. A amostra foi constituída por 60 mulheres na faixa etária acima de 40 anos e em período pós-menopausa que foram encaminhadas ao Serviço de Radiologia da Faculdade de Odontologia da UFRGS durante o ano de 2006, com indicação de radiografia periapical da região de pré-molares e/ou molares inferiores e que realizaram, no mesmo período, um exame de densitometria óssea pela técnica de absorciometria por raios X de emissão dual (DXA) nas regiões de coluna lombar e fêmur proximal. Com base nos resultados da densitometria, as pacientes foram divididas em dois grupos (normal e com perda óssea) e para cada radiografia foram obtidos os valores de densidade radiográfica e 14 variáveis morfológicas do trabeculado. As variáveis clínicas utilizadas foram idade e IMC. A análise estatística por árvores de classificação e regressão foi utilizada para testar o poder preditivo dos fatores de risco - clínicos e radiográficos - na classificação das pacientes nos grupos normal e com perda óssea. A idade e o número de pontos terminais/periferia, seguido da periferia/área trabecular, densidade radiográfica e por último o IMC foram as variáveis que melhor dividiram as pacientes em normais e com perda óssea. Esse estudo conclui que a combinação das variáveis clínicas e radiográficas obtidas por meio de radiografias periapicais é capaz de identificar pacientes com perda de massa óssea. Dessa forma, o cirurgião-dentista está apto a identificar as pacientes com risco de desenvolver osteoporose e encaminhá-las para avaliação médica. / The aim of this study was to determine whether periapical radiograph can be used to identify patients with low bone mass. This goal was accomplished by combining trabecular morphologic analysis with radiographic density measurements as well as with clinical parameters. The study subject consisted of 60 postmenopausal women over forty years of age who were conducted to the Dental Radiology Service of UFRGS School of Dentistry during the year of 2006 to take a periapical radiograph of mandibular premolar and/or molar regions. Additionally, measurements of lumbar spine and proximal femur’s bone mineral density were obtained from these patients by dual-energy X-ray absortiometry, during the same period. The subjects were classified either as normal or with low bone mass according to their bone mineral density. Radiographic density measurements and fourteen morphologic features were obtained from each dental radiograph by the use of digital image processing software. The clinical variables considered were subject´s age and bone mass index (BMI). Classification and regression tree (CART) analysis was used to test the predictive power of clinical and radiographic risk factors to classify individual in either normal or low bone mass classes. CART analysis found that the most important variables for classifying subjects were age, number or terminal points/periphery, periphery/trabecular area, radiographic density and BMI. This study showed that the combination of clinical and radiography factors can identify individuals with low bone mineral density with higher accuracy than either one of the factor taken individually. As a consequence, dentists are able to pre-screen patients with abnormally high risk for developing osteoporosis through standard routine exams and conduct these patients to further medical evaluation whenever necessary.

Orientadores: Aarão Mendes Pinto Neto, Ilka de Fátima Santana Ferreira Boin / Dissertação (mestrado) - Universidade Estadual de Campinas. Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T10:07:53Z (GMT). No. of bitstreams: 1 Baccaro_LuizFranciscoCintra_M.pdf: 2066232 bytes, checksum: 25566bdc178a22d90d8003f008dd9ed2 (MD5) Previous issue date: 2010 / Resumo: Objetivos: avaliar a massa óssea e os fatores associados em mulheres submetidas a transplante de fígado em acompanhamento no Ambulatório da Unidade de Transplante Hepático do Hospital das Clínicas da Faculdade de Ciências Médicas da Universidade Estadual de Campinas Sujeitos e Métodos: estudo de corte transversal com mulheres transplantadas hepáticas em acompanhamento no Ambulatório da Unidade de Transplante Hepático do Hospital das Clínicas da Faculdade de Ciências Médicas da Universidade Estadual de Campinas. Foram incluídas todas as mulheres que realizaram transplante hepático há pelo menos um ano e com idade igual ou superior a 35 anos. Foram identificadas 33 mulheres que preenchiam os critérios de inclusão. Dessas, 6 não responderam ao contato telefônico e 4 não quiseram participar, sendo o número final de mulheres participantes igual a 23. Foi realizada entrevista, sempre pelo mesmo pesquisador, onde foram obtidos dados clínicos, sócio-demográficos e realizados exame físico geral e ginecológico. Após a avaliação clínica as mulheres foram encaminhadas para realização de exames laboratoriais (aspartato aminotransferase, alanina aminotransferase, fosfatase alcalina, gama glutamiltransferase, bilirrubina total e frações) e densitometria óssea de coluna lombar e fêmur. A análise estatística foi realizada através do teste exato de Fisher, OR simples e coeficiente de correlação de Spearman. Todas assinaram o termo de consentimento livre e esclarecido previamente à entrevista, e o estudo foi aprovado no Comitê de Ética em Pesquisa da UNICAMP. Resultados: A média de idade das mulheres foi de 52,5 ± 10,9 anos e a média de tempo pós transplante foi de 5,8 ± 3,1 anos. Do total de 23 mulheres incluídas no estudo, 56,5% apresentaram massa óssea alterada. Estar na pós menopausa foi fator de risco para diminuição da massa óssea: OR 69,0 (95% IC 2,89-1647,18; p < 0,0001). Ter idade superior a 44 anos na realização do procedimento aumentou o risco para diminuição da massa óssea: OR 49,50 (95% IC 3,84-638,43; p <0,0001). Ter idade superior a 49 anos aumentou o risco para diminuição na massa óssea: OR 13,33 (95% IC 1,78-100,15; p = 0,0123). Apresentar um período de tempo maior que 5,8 anos da realização do transplante foi fator protetor para diminuição na massa óssea: OR 0,11 (95% IC 0,02-0,78; p = 0,0361). Conclusão: mais da metade das mulheres transplantadas hepáticas apresentaram diminuição da massa óssea. O estado menopausal, a idade, a idade ao transplante e o tempo pós transplante foram os fatores associados à alteração da massa óssea em mulheres transplantadas hepáticas / Abstract: Objectives: to evaluate bone mass and risk factors associated with bone mass alterations in women undergoing liver transplantation followed at the Liver Transplant Outpatient Unit in the Clinics Hospital of the Campinas State University Medical School. Subjects and Methods: a cross-sectional study of women undergoing liver transplantation and followed at the Liver Transplant Outpatient Unit in the Clinics Hospital of the Campinas State University Medical School was carried out. All women aged 35 years or older who had received a liver transplant at least one year before enrollment were included in the study. Thirty-three women satisfied the criteria for study inclusion. Of the total, 6 did not respond to telephone contact and 4 declined to participate. As a result, the final number of women participating in the study was 23. An interview was conducted always by the same investigator for collection of clinical and sociodemographic data, as well as the performance of a general physical and gynecological examination. After clinical evaluation, the women underwent laboratory tests (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, total and fractionated bilirubin) and bone mineral density measurement of the lumbar spine and femur. Statistical analysis was performed by Fisher's exact test, simple OR and Spearman's rank correlation coefficient. All women signed a written informed consent term prior to the interview. The study was approved by the Research Ethics Committee of UNICAMP. Results: The mean age of the women was 52.5 ± 10.9 years and mean time since transplantation was 5.8 ± 3.1 years. Of the total number (23) of women included in the study, 56.5% had alteration in bone mass. Being postmenopausal was a risk factor for decreased bone mass: OR 69.0 (95% CI 2.89-1647.18; p < 0.0001). Being over 44 years of age at the time of the surgical procedure increased the risk for decreased bone mass: OR 49.50 (95% CI 3.84-638.43; p < 0.0001). Being over 49 years of age increased the risk for decreased bone mass: OR 13.33 (95% CI 1.78-100.15; p = 0.0123). A period of time longer than 5.8 years since transplantation was a protective factor for decreased bone mass: OR 0.11 (95% CI 0.02-0.78; p = 0.0361). Conclusion: more than 50% of the women undergoing liver transplantation had decreased bone mass. Menopausal status, current age, age at the time of transplantation and time since transplantation were factors associated with bone mass alterations in women receiving a liver transplant / Mestrado / Tocoginecologia / Mestre em Tocoginecologia

Orientador: Celio Kenji Miyasaka / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-04T20:07:29Z (GMT). No. of bitstreams: 1 Netto_ClaudiaCardoso_M.pdf: 2097172 bytes, checksum: 26da5ef46aaf69a40d89565e18139111 (MD5) Previous issue date: 2005 / Mestrado / Nutrição Experimental e Aplicada à Tecnologia de Alimentos / Mestre em Alimentos e Nutrição

Orientador: Plauto Christopher Aranha Watanabe / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-13T08:02:53Z (GMT). No. of bitstreams: 1 Pedrosa_EsioFortalezaNascimentoChaves_M.pdf: 2734521 bytes, checksum: ab04697c2441e91af05be90051625d6d (MD5) Previous issue date: 2009 / Resumo: Existem diversos métodos para avaliar a qualidade óssea através de sua densidade. Estes métodos variam no custo, disponibilidade e na dose de radiação. O cirurgião-dentista atua nos elementos dentários e nas estruturas de suporte dos maxilares e mandíbula, componentes do sistema estomatognático. Nas últimas décadas têm se pesquisado muito a respeito da qualidade óssea das estruturas de suporte dos elementos dentários, principalmente na mandíbula, com convincentes evidências de perda óssea bucal associada com a osteoporose, particularmente um aumento da porosidade cortical do osso alveolar e corpo mandibular. O Objetivo deste estudo foi avaliar a correlação de três aspectos da qualidade óssea mandibular, em radiografias panorâmicas, correlacionando-os com medidas de densidade óssea mineral (DOM) do DEXA realizados no radio, coluna e fêmur. Os resultados apresentaram correlação significante entre a classificação morfológica do córtex (CC) e a espessura da cortical basal mandibular com a DOM. Não houve correlação entre os fatores dimensão fractal (DF) e porcentagem de pixels pretos (ET) com a DOM. Pode-se concluir que é possível referenciar pacientes para o DEXA com a finalidade de pesquisar a baixa massa óssea mineral pelas análises da cortical inferior da mandíbula. / Abstract: There are several methods to evaluate the bone quality by the density. These methods vary in cost, availability and the radiation dose. The dentist works on teeth and in the maxilla and mandible support structures, components of the stomatognathic system. Recently, it has been searched too much about the bone quality of the teeth support structures, especially in the jaw with evidences of oral bone loss associated with osteoporosis, particularly an increase in cortical porosity of the alveolar bone and mandibular body. The aim of this study was to evaluate the interrelationship of three aspects of mandibular bone quality on panoramic radiographs, correlating them with measures of bone mineral density (BMD) of DEXA performed in radio, spine and femur. The results showed a significant correlation between the cortex morphological classification and cortex thickness with lower BMD. There was no correlation between the fractal dimension (FD) factors and black pixels (ET) percentage with the BMD. It could be concluded that it is possible to refer patients for DEXA in order to search for low bone mineral analysis of the lower mandibular cortex. / Mestrado / Radiologia Odontologica / Mestre em Radiologia Odontológica

Dentoflex / LaboratÃrio Servier do Brasil / A integraÃÃo dos implantes dentÃrios no osso tem sido amplamente relatada nas Ãltimas dÃcadas desde os trabalhos originais de Branemark e co-autores. O uso de implantes dentÃrios de titÃnio no tratamento de pacientes edÃntulos ou parcialmente edÃntulos tem se tornado uma alternativa para restauraÃÃo funcional e estÃtica, entretanto esses resultados dependem da quantidade e da qualidade do osso maxilar ou mandibular. Osteoporose à uma doenÃa que influencia a qualidade do tecido Ãsseo, tornando-o susceptÃvel à fratura. RelaÃÃo importante tem sido descrita entre massa Ãssea oral e esquelÃtica em mulheres pÃs-menopausa. A osteoporose tem sido considerada um fator de risco para a osseointegraÃÃo de implantes dentÃrios, embora o assunto ainda seja bastante controverso. O ranelato de estrÃncio à uma nova terapia para o tratamento e prevenÃÃo da osteoporose, que dissocia a formaÃÃo Ãssea da reabsorÃÃo Ãssea permitindo continuada produÃÃo de osso enquanto diminui a sua reabsorÃÃo. O objetivo do presente trabalho foi determinar, em coelhos, o efeito da terapia sistÃmica com ranelato de estrÃncio sobre o tempo de osseointegraÃÃo de implantes dentÃrios baseado nos valores do torque para a sua remoÃÃo. Sessenta e quatro implantes dentÃrios de titÃnio idÃnticos foram, entÃo, instalados, seguindo protocolo cirÃrgico padronizado, na distal do fÃmur e proximal da tÃbia, bilateralmente, de 16 coelhos brancos da raÃa Nova ZelÃndia (64 implantes no total). Uma semana antes da instalaÃÃo dos implantes, foi iniciada a administraÃÃo de doses de ranelato de estrÃncio (625mg/kg/dia) a 8 coelhos prorrogada atà o sacrifÃcio desses animais. Os outros 8 coelhos pertenciam ao grupo controle, sem medicaÃÃo. Um coelho de cada grupo foi sacrificado com 15, 30, 45, 60, 75, 90, 105 e 120 dias e os valores do torque para a remoÃÃo dos implantes foi determinado por um torquÃmetro digital. A anÃlise dos dados desses torques mostrou que nÃo houve nenhuma diferenÃa estatÃstica entre o grupo experimental e o grupo controle. Com base nos achados do presente trabalho, concluiu-se que o tempo de 15 atà 120 dias de uso de ranelato de estrÃncio nÃo interferiu no tempo de osseointegraÃÃo. / The integration of titanium dental implants in bone has been reported extensively over the last few decades beginning with the original work of Branemark and co-workers. The use of titanium endosseous dental implants in the treatment of edentulous or partially edentulous patients has become an alternative to restore function and esthetics, however, this results depend on the quantity and quality of the maxillary or mandibular bone. Osteoporosis is a disease that influences the quality of bone tissue such that it may become susceptible to fracture. Significant relationship have been reported between oral bone and skeletal bone mass in postmenopausal women. Osteoporosis could, therefore be considered a risk factor for osseointegration of dental implants, but this is still controversial. Strontium ranelate is a new therapy for the treatment and prevention of osteoporosis that may dissociate bone formation and bone resorption by allowing continued production of bone while decreasing bone resorption. The purpose of this study was to determine the effect of systemic strontium ranelate therapy on early dental implant osseointegration based on torque-removal values in rabbits. Sixty-four identical titanium dental implants were placed using a standardized surgical protocol in the bilateral distal femur and proximal tibia of 16 New Zealand white rabbits (64 implants total). One week before implant placement, 8 rabbits were given doses of strontium ranelate (625mg/kg/day) until euthanized. The other 8 rabbits were untreated controls. One rabbit of each group were sacrificed in time of 15, 30, 45, 60, 75, 90, 105, 120 days, and torque-removal values were determined using a digital torque wrench for all implants. Analyses of torque data showed no statistical differences between the strontium ranelate and control groups. Based on the findings of this study, we can conclude that the time of 15 to 120 days of strontium ranelate administration does not interfere with the timing of early dental implant osseointegration in an animal model.

Orientador: Solange Maria de Almeida / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-04T04:01:51Z (GMT). No. of bitstreams: 1 Silva_MarilianiChicarellida_D.pdf: 2982400 bytes, checksum: 4a42cb3e53e884e2e38412e79724b993 (MD5) Previous issue date: 2005 / Resumo: Sendo a osteoporose uma condição que acarreta fragilidade óssea e a radiação ionizante dificuldades no processo de reparação, o experimento foi idealizado com a finalidade de verificar-se o efeito da associação da deficiência de estrogênio e da radiação ionizante no processo de reparação óssea. Rattus Norvegicus Albinus Wistar, compuseram 4 grupos experimentais: controle, ovariectomizado, irradiado e ovariectomizado/irradiado, cuja deficiênica de estrogênio foi induzida através da ovariectomia. Após a comprovação da deficiência de estrogênio, nos grupos ovariectomizados, todos os grupos de animais foram submetidos à confecção de defeito ósseo em suas tíbias. Os grupos irradiado e ovariectomizado/irradiado tiveram irradiados os membros inferiores com 8 Gy de radiação gama, após 3 dias do procedimento cirúrgico. Transcorrido 7, 14, 21, 28 e 45 dias, o processo de reparação óssea foi avaliado, utilizando-se para a avaliação morfológica a Hematoxilina-Eosina e o Tricrômico de Mallory. Também foram realizadas a análise da birrefringência (coloração com Picrosírius); a análise da densidade volumétrica (coloração com Hematoxilina- Eosina) e a análise ultra-estrutural (Microscopia Eletrônica de Varredura). Os resultados encontrados indicaram que houve atraso do processo de reparação, no grupo ovariectomizado/irradiado, no qual a associação da deficiência de estrogênio e radiação ionizante acarretou uma diminuição na produção de osso neoformado e acelerou o processo de reabsorção / Abstract: As osteoporosis is a condition that causes bone fragility and ionization radiation makes the repair process difficult, the experiment was carried out to check the effect of the association of estrogen deficiency and ionization radiation on the bone repair process. The 4 experimental groups of female Wistar rats were subjected to the following conditions: control, ovariectomized, irradiated and ovariectomized/irradiated, with estrogen deficiency being induced through ovariectomy. After estrogen deficiency was confirmed, all the animals in the ovariectomized groups had a bone defect made in their tibias. The irradiated groups and ovariectomized/irradiated had their inferior members irradiated with 8 Gy of gama radiation 3 days after the surgical procedure. After 7, 14, 21, 28 and 45 days had elapsed, the bone repair process was evaluated, Hematoxylin-Eosin and Mallory¿s Tricomic being used for the morphologic evaluation. The following analyses were also carried out: birefringence analysis (Picrosirius Stain); the volumetrical density analysis (hematoxylin-eosin stain) and the ultra-structural analysis (Electronic Scanning Microscopy). The results found indicated that there was delay in the repair process in the ovariectomized/irradiated group, in which the association of the estrogen deficiency and ionization radiation caused a decrease in the production of neo- formed bone and accelerated the reabsorption process / Doutorado / Radiologia Odontologica / Doutor em Radiologia Odontológica

Bone has the capacity to regenerate itself, however for challenging defects such as non-uniform factures, repair can be problematic. A similar challenge is presented in the repair of osteoporotic bone. Osteoporotic bone becomes increasingly porous and brittle and the risk of fracture is greatly increased. A drug mimic, poly(vinyl phosphonic acid – co – acrylic acid)(PVPA), has been incorporated into FDA approved poly(ε-caprolactone)(PCL), and aims to mimic the action of bisphosphonates to reduce the activity of osteoclasts. The PVPA polymer contains pendant phosphonic acid groups which are hypothesised to mimic the P-C-P backbone found in bisphosphonates. The PCL/PVPA scaffold has been found to have sufficient mechanical strength in order to be used as a bone void filler as well as providing a hydrophilic surface for superior cell attachment. The substrate has been found to significantly enhance the deposition of collagen, alkaline phosphatase activity and the expression of osteocalcin. Alizarin red staining revealed an increase in the rate of mineralisation in the presence of the drug mimic. The PCL/PVPA substrates have been suggested to induce osteoblast cells from a proliferative phase to a mineralisation stage. This is believed to be due to the presence of phosphorous within the scaffold which could lead to the critical concentration required for the initiation of mineralisation being reached more rapidly and effectively. The PVPA polymer has been found to mimic the action of bisphosphonates by inducing osteoclast apoptosis in vitro, and its actions of osteoclast apoptosis are comparable to that of Alendronate, a commonly administered bisphosphonate. A critical size defect model has demonstrated that the PVPA polymer has the ability to heal critical size defects; the healing potential was two fold greater than the control PCL substrate. Initial in vivo studies using a subcutaneous model demonstrated an improvement in mineralisation in the presence of PVPA. Untreated PCL/PVPA substrates displayed a high level of branched blood vessel formation, essential for healthy bone formation. However PVPA samples pre-treated with VEGF, hindered blood vessel formation and the infiltration of cells. This suggests that the PVPA alone is capable of inducing neovascularisation without the addition of VEGF. The findings suggest that the PCL/PVPA system could be used to treat challenging bone defects such as non-unions and osteoporotic fractures.

Abstract Genetic factors and their resulting phenotypes were evaluated in three different bone disorders: osteogenesis imperfecta (OI), juvenile idiopathic osteoporosis (JIO), and stress fractures. The spectrum of the OI phenotypes caused by mutations in the COL1A1 and COL1A2 genes is well defined, but the mechanisms by which the variations affect the hearing phenotype are not well-known. A total of 54 Finnish OI patients with previously diagnosed hearing loss, or aged 35 or more years, were analyzed here for mutations in COL1A1, or COL1A2. Altogether, 49 mutations were identified, of which 41 were novel. No correlation was observed between the mutated gene, or the mutation type, and the hearing pattern. This indicates that the basis of hearing loss in OI is complex, and is a result of multifactorial, still unknown genetic effects, or of variable expressions of the COL1A1 and COL1A2 genes. JIO presents peri-pubertally as an acute symptomatic osteoporosis (bone pain and fractures) in otherwise healthy children, and no underlying cause has yet been identified for this disorder. Here, the analysis of the low-density lipoprotein receptor-related protein 5 gene (LRP5) in 20 patients with JIO revealed two missense mutations (A29T and R1036Q) and one frameshift mutation (C913fs) in 3 of the patients. The LRP5 gene has recently been shown to be also involved in osteoporosis-pseudoglioma syndrome and a high-bone-mass phenotype. Stress fractures are a significant problem among athletes and soldiers. Genetic factors may increase the fracture risk, but no susceptibility genes have yet been identified. Seven genes involved in bone metabolism, or pathology, were studied in terms of their roles in stress fracture. No disease-causing, or predisposing variations were found in the candidate gene, or association analyses, but a highly significant association was found between the phenotype and a vitamin D receptor (VDR) haplotype, TGT, which is composed of three polymorphic sites, FokI, BsmI and TaqI. We showed that femoral neck stress fractures are associated with a certain VDR haplotype, accounting for a five-fold increase in the risk of developing stress fractures, with an associated attributable risk of 12%. The results of this study show that genetic factors play a role in different pathological bone phenotypes. These findings provide new information on the pathogenesis of the disorders and for the development of genetic testing and targeted treatment for the disorders.