Orientador: Enilson Antonio Sallum / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-14T12:01:49Z (GMT). No. of bitstreams: 1 Santamaria_MauroPedrine_D.pdf: 1906873 bytes, checksum: 996991755e8909f6c85dd127ec284d0f (MD5) Previous issue date: 2009 / Resumo: Recessões gengivais estão freqüentemente associadas às lesões cervicais não-cariosas. O tratamento dessa lesão combinada é um desafio. Trabalhos recentes têm apresentado resultados de tratamento conjunto de cirurgia periodontal e dentística restauradora para tratamento da lesão combinada. Porém nenhum trabalho demonstrou resultados de longo prazo desse tipo de abordagem, além de variações desse tratamento e dos fatores anatômicos locais que poderiam influenciar na resultado dessas terapias. Portanto, os objetivos do presente estudo foram: 1. Apresentar os resultados após 2 anos de tratamento de recessões gengivais associadas à lesões cervicais tratadas com retalho posicionado coronariamente (RPC) sozinho ou associado à restauração de ionômero de vidro modificado por resina (CIV). 2. Avaliar os resultados, após 6 meses de tratamento do enxerto de tecido conjuntivo (ETC) associado ou não à restauração de CIV para tratamento da lesão combinada. 3. Avaliar a possível influência das características anatômicas locais no recobrimento das lesões combinadas tratadas pelas técnicas do retalho posicionado coronariamente e pelo enxerto de tecido conjuntivo. Para o primeiro objetivo, foi realizado um estudo clínico controlado e randomizado que foram incluídos 16 indivíduos apresentando duas recessões gengivais bilaterais associadas à lesões cervicais em caninos ou pré-molares superiores. Os defeitos foram tratados com RPC sozinho ou associado à restauração de CIV. Os resultados não demonstraram diferença significante entre os grupos após 2 anos com relação à redução da recessão gengival, ganho no nível clínico de inserção e sangramento à sondagem. Para o segundo objetivo, foi realizado um estudo clinico controlado e randomizado que foram incluídos 40 indivíduos apresentando uma recessão gengival associada à lesão cervical em caninos ou pré-molares superiores. Os defeitos foram tratados com ETC sozinho ou associado à restauração de CIV. Os resultados não demonstraram diferença estatisticamente significante entre os grupos após 6 meses com relação à redução da recessão gengival, ganho no nível clínico de inserção, ganho de tecido queratinizado e sangramento à sondagem. No entanto, o grupo que recebeu ETC e a restauração de CIV foi estatisticamente melhor na redução da hipersensibilidade dentinária. Para o terceiro objetivo, as características anatômicas locais dos indivíduos dos dois estudos clínicos prévios foram medidas e analisadas através de regressão linear multipla. Os resultados demonstraram correlação estatisticamente significante entre a profundidade da lesão cervical não-cariosa e o a redução na recessão gengival quando RPC foi utilizado de forma isolada. A altura da lesão combinada também apresentou correlação estatisticamente significante com a redução da recessão gengival para ambos os estudos. Além disso, a deiscência óssea apresentou correlação estatisticamente significante quando ETC foi utilizado. Dentro dos limites desse estudo, pode-se concluir que a restauração de ionômero de vidro modificado por resina parece não interferir no recobrimento da lesão combinada após 2 anos de avaliação, quando o retalho posicionado coronariamente foi utilizado e após 6 meses quando o enxerto de tecido conjuntivo foi utilizado. A profundidade da lesão cervical pode ter alguma influência quando RPC é utilizado e a deiscência óssea parece não interferir negativamente no recobrimento quando ETC foi utilizado. / Abstract: Gingival recessions are frequently associated with non-carious cervical lesion. Previous studies have shown results from a combined treatment (periodontal surgery plus restoration of the cervical lesion) to deal with the association of these two lesions. However, there is lack of information regarding the long term evaluation of the combined treatment. Moreover, no additional information regarding other surgical techniques and the influence of the local anatomical characteristics have not been evaluated. Thus, the objectives of this study were: 1. Evaluate the 2-year-follow-up outcome of the treatment of gingival recession associated with non-carious cervical lesions by coronally advanced flap alone (CAF), or in combination with a resin-modified glass ionomer restoration 2. Evaluate the 6-month-follow-up outcome of the treatment of gingival recession associated with cervical lesion by connective tissue graft alone (CTG), or in combination with a resin-modified glass ionomer restoration, and 3. Evaluate the possible influence of local anatomy on the amount of soft tissue coverage achieved and on the clinical attachment gain by the use of CAF and CTG, alone or in combination with resin-modified glass ionomer restoration to treat the combined defect. For the first objective, 16 patients with bilateral Miller Class I buccal gingival recessions, associated with non-carious cervical lesions were selected. The defects received either CAF alone or CAF plus a resin-modified glass ionomer restoration. The results showed that both groups showed statistically significant soft tissue coverage. The differences between groups were not statistically significant in reduction of gingival recession, gain in the clinical attachment level, and bleeding on probing after 2 years. For the second objective, 40 patients with Miller Class I buccal gingival recessions, associated with non-carious cervical lesions were enrolled. The defects were randomly assigned to receive either CTG alone or CTG plus a resin-modified glass ionomer restoration. The results showed that both groups showed statistically significant soft tissue coverage. The differences between groups were not statistically significant in gingival recession, gain in the clinical attachment level, and bleeding on probing, after 6 months. However, the group CTG plus the restoration showed statistically significant reduction in dentin sensitivity when compared to CTG alone. For the third objective, the local anatomical characteristics from the patients enrolled in the 2 previous studies were correlated with the reduction of the gingival recession and the gain in the clinical attachment level using Stepwise Multivariate Linear Regression. The results showed that the cervical lesion depth was significantly correlated with reduction in gingival recession, when considering data from the CAF group. The cervical lesion height was statistically correlated with the reduction in gingival recession when the two groups were analyzed. Additionally, the bone level was statistically correlated with reduction in gingival recession when evaluating the CTG group. Within the limits of the present study it can be concluded that the presence of the resin-modified glass ionomer restoration may not interfere with the amount of coverage achieved either by CAF after 2 years or CTG after 6 months. The cervical lesion depth may have some influence on the final coverage achieved when CAF is applied and the bone level may not play any role when CTG is applied. / Doutorado / Periodontia / Doutor em Clínica Odontológica

A estimativa de idade pela contagem das linhas incrementais de cemento (LC) adicionadas à idade média de erupção do dente analisado é um método tido como preciso e confiável por alguns autores, enquanto outros o rejeitam afirmando não haver forte correlação entre idade real e estimada. O objetivo do estudo foi avaliar a técnica descrita e verificar se há influência de patologias bucais na estimativa de idade, analisando-se, além do número de LC, correlação entre espessura de cemento e idade real. Foram preparadas por desgaste 31 lâminas transversais, de aproximadamente 30 m, de 25 dentes recém extraídos. As lâminas foram observadas, fotografadas e medidas em microscopia óptica. As LC das imagens foram realçadas com uso do software Image J 1.43s e as contagens foram feitas por um observador e dois observadores-controle. Houve correlação moderada de 0.58 para toda a amostra, com erro médio de 9,7 anos. Para dentes com alterações periodontais, a correlação foi de 0.03 e erro médio de 22,6 anos. Para dentes sem alterações periodontais, a correlação foi de 0.74 e erro médio de 1,6 anos. A espessura de cemento teve correlação com idade real de 0.69 para toda amostra, 0.25 para dentes com problemas periodontais e 0.75 para dentes sem problemas periodontais. A técnica das LC associada à medição de espessura de cemento mostrou-se confiável para dentes sem patologias periodontais, porém em dentes com patologias periodontais ou histórico/quadro clínico desconhecido, recomenda-se a realização de exames macroscópicos conjuntos para comparação. / Age estimation by counting incremental lines in cementum added to the average age of tooth eruption is considered an accurate and reliable method by some authors, while others reject it stating no strong correlation between estimated and actual age. The aim of this study was to evaluate this technique and check the influence of oral conditions on age estimation by analyzing both the number of cementum lines as well as the correlation between cementum thickness and actual age, on diseased teeth. Thirty one undecalcified ground cross sections of approximately 30 m, from 25 freshly extracted teeth were prepared, observed, photographed and measured. The images were enhanced with the use of software and the counts were made by one observer and two control-observers. There was moderate correlation ((r)=0.58) for the entire sample, with mean error of 9.7 years. For teeth with periodontal pathologies, the correlation was 0.03 with a mean error of 22.6 years. For teeth without periodontal pathologies, the correlation was 0.74 with mean error of 1.6 years. There was correlation of 0.69 between cementum thickness and actual age for the entire sample, 0.25 for teeth with periodontal problems and 0.75 for teeth without periodontal pathologies. The cementum lines technique associated with the measurement of cementum thickness was reliable for teeth without periodontal pathologies, but in periodontally diseased teeth or teeth with unknown history/clinical background, parallel macroscopic examinations should be conducted.

L’estimation de l’âge au décès d’individus découverts en contexte médico-légal ou ar-chéologique est un sujet fondamental. La cémentochronologie fondée sur le dépôt annuel de cément acellulaire est une technique parmi les plus performantes dont l’exactitude est appréciée dans de nombreuses publications. Cependant, le manque de standardisation ralentit l’adoption de cette méthode et freine l’étude de la précision qui demeure méconnue tout comme l’impact des conditions taphonomiques sur sa fiabilité. Le premier objectif de ce travail est de mesurer la concordance des estimations effectuées, donc la précision, puis d’évaluer l’exactitude, donc la qualité de l’accord entre l’âge estimé et l’âge chronologique, en appliquant un protocole standardisé et certifié ISO-9001 pour s’affranchir des biais inhérents à la préparation. Le second objectif est d’apprécier l’impact des affections taphonomiques trop souvent négligées. La collecte des données à partir de préparations histologiques dentaires représente une opération coûteuse en temps et constitue un obstacle majeur pour conduire des études cémentochronologiques. Nous nous fixons comme autre objectif d’expérimenter un logiciel de comptage semi-automatique, fruit d’une collaboration entre anthropologues (UTML) et développeurs (FEI Visualization Sciences Group). Pour atteindre ces buts, l’étude porte sur 2000 lames histologiques réalisées à partir de 400 canines. 200 canines sont issues de collections de référence dont l’âge, le sexe, l’intervalle postmortem et la durée d’inhumation des sujets sont connus. Afin d’apprécier l’influence de la taphonomie sur la lisibilité et la précision et d’étudier l’applicabilité de la méthode à du matériel ancien, 200 canines extraites de sujets archéologiques datés entre le XIIe et le XVIIIe siècle sont intégrées à l’étude. Précision et exactitude sont approchées pour chaque classe d’âge et en tenant compte des intervalles post-mortem et des affections taphonomiques, mettant ainsi en évidence une fiabilité qui est fonction de l’âge du sujet, mais aussi de l’état de conservation des tissus. Ce travail vise, sur un échantillon standardisé conséquent, à amener une discussion sur les performances de la cémentochronologie à l’échelle individuelle et populationnelle, à apporter des recommandations et proposer un modèle de prédiction pour minimiser les différences entre âge estimé et âge chronologique. / Age at death estimation is a fundamental component of creating a biological profile in forensic and bioarchaeological contexts. Cementochronology based on annual deposition of acellular cementum is one of the most effective ageing techniques, and its accuracy, i.e. the agreement between estimated age and chronological age, is acknowledged in many publications. However, the lack of standardization slows down the adoption of this method and hinders the evaluation of its precision that remains unknown as well as the impact of taphonomical processes. The first objective of this thesis is to measure the agreement between cementum estimates, i.e. the precision, and then to assess the accuracy through the evaluation of the quality of the accordance between chronological age and estimates based on a standardized and ISO-9001 certified protocol to overcome bias due to sample preparation. The second objective is to gauge the impact of taphonomical effects too often neglected. Counting cementum increments on histological preparations is time-consuming and represents a major difficulty to perform cementochronological studies. Another goal is to experiment a semi-automatic program resulting from a col-laboration between anthropologists (UTML) and software developers (FEI Visualization Sciences Group). To achieve these goals, our study is based on 2000 histological sections from 400 canines. 200 canines are derived from reference collections with documented age, sex, postmortem interval and burial duration. In order to grasp the influence of taphonomy on slices readability and on precision and to investigate the applicability of this method on ancient material, 200 canines extracted from archaeological assemblages dated between the XIIth century and XVIIIth century are included in the study. Accuracy and precision are assessed for each age group in considering post-mortem intervals and taphonomical conditions and show a reliability influenced by age but also by tissue preservation. This work aims, on a large standardized sample, to discuss cementochronology’s performance for individual and population approaches, to provide recommen-dations and to propose a prediction model to reduce differences between estimated age and chronological age.

Orientador: Luis Carlos Spolidório / Banca: Benedicto Egbert Corrêa de Toledo / Banca: Carlos Rossa Júnior / Banca: Maria Ângela Naval Machado / Banca: Maria Lúcia Rubo de Rezende / Resumo: Tacrolimus (FK506) é uma droga imunossupressora usada em transplantes de órgãos e também como terapia alternativa em pacientes com rejeição refratária de enxertos ou intolerância à ciclosporina A (CsA), sem os efeitos adversos atribuídos freqüentemente à CsA. Atualmente não há estudos que explorem os efeitos da administração de FK506 por longos períodos sobre o periodonto. Ë sugerido também que terapias imunossupressivas, principalmente com FK506, possam ser um importante fator no desenvolvimento de Diabetes mellitus pós-transplantes (PTDM). Existem alguns estudos explorando os efeitos do FK506 por longos períodos no desenvolvimento da PTDM em protocolos animais. Assim os objetivos do estudo foram avaliar os efeitos da terapia com FK506 por longos períodos sobre os tecidos gengivais, metabolismo do osso alveolar e do cemento de ratos, bem como os efeitos sobre os níveis glicêmicos. Com relação ao metabolismo ósseo, houve uma tendência de diminuição, estatisticamente significante, dos níveis de ALP em todos os períodos tratados com FK506, sendo que com os níveis de cálcio apenas um aumento em 240 dias de tratamento, quando comparados com os grupos controles. Assim, nós podemos concluir que o FK506 em longos períodos pode levar os efeitos deletérios sobre os tecidos gengivais e pode ser dependente da idade, mas não causaria efeitos negativos sobre o osso alveolar e nem ao cemento. E ainda em relação aos níveis séricos de glicemia, os efeitos negativos da terapia com FK506 também são dependentes do tempo. / Abstract: Tacrolimus (FK506) is an immunosuppressive drug in organ transplantation and it is also an alternative therapy used for transplant patients with either refractory graft rejection or intolerant to cyclosporine A (CsA), without the adverse effects frequently attributed to CsA therapy. Nevertheless there are not studies exploring the effects of long-term FK506 therapy on periodontium. It has been suggested that immunosuppressive therapy, mainly FK506, may be an important factor in the development of post-transplantation diabetes mellitus (PTDM). There is a lack of studies exploring the effects of a long-term FK506 on PTDM in animal's protocols. The objectives of the present study were to evaluate the effects of long-term therapy with FK506 on the gingival tissue, alveolar bone metabolism and cementum in rats and the deleterious glycemic effects of long-term therapy with FK506. There was a tendency of increase of serum glycemia level in the initial periods (60 and 120 days). Within the limits of this experimental study, it can be concluded that the deleterious gingival effects of FK506 administration may be time and age related side effects and that have not the negative effects of FK506 administration long-term on the alveolar bone and cementum. It can be concluded that the deleterious glycemia effects of FK506 therapy may be time related side effects. / Doutor

A estimativa de idade pela contagem das linhas incrementais de cemento (LC) adicionadas à idade média de erupção do dente analisado é um método tido como preciso e confiável por alguns autores, enquanto outros o rejeitam afirmando não haver forte correlação entre idade real e estimada. O objetivo do estudo foi avaliar a técnica descrita e verificar se há influência de patologias bucais na estimativa de idade, analisando-se, além do número de LC, correlação entre espessura de cemento e idade real. Foram preparadas por desgaste 31 lâminas transversais, de aproximadamente 30 m, de 25 dentes recém extraídos. As lâminas foram observadas, fotografadas e medidas em microscopia óptica. As LC das imagens foram realçadas com uso do software Image J 1.43s e as contagens foram feitas por um observador e dois observadores-controle. Houve correlação moderada de 0.58 para toda a amostra, com erro médio de 9,7 anos. Para dentes com alterações periodontais, a correlação foi de 0.03 e erro médio de 22,6 anos. Para dentes sem alterações periodontais, a correlação foi de 0.74 e erro médio de 1,6 anos. A espessura de cemento teve correlação com idade real de 0.69 para toda amostra, 0.25 para dentes com problemas periodontais e 0.75 para dentes sem problemas periodontais. A técnica das LC associada à medição de espessura de cemento mostrou-se confiável para dentes sem patologias periodontais, porém em dentes com patologias periodontais ou histórico/quadro clínico desconhecido, recomenda-se a realização de exames macroscópicos conjuntos para comparação. / Age estimation by counting incremental lines in cementum added to the average age of tooth eruption is considered an accurate and reliable method by some authors, while others reject it stating no strong correlation between estimated and actual age. The aim of this study was to evaluate this technique and check the influence of oral conditions on age estimation by analyzing both the number of cementum lines as well as the correlation between cementum thickness and actual age, on diseased teeth. Thirty one undecalcified ground cross sections of approximately 30 m, from 25 freshly extracted teeth were prepared, observed, photographed and measured. The images were enhanced with the use of software and the counts were made by one observer and two control-observers. There was moderate correlation ((r)=0.58) for the entire sample, with mean error of 9.7 years. For teeth with periodontal pathologies, the correlation was 0.03 with a mean error of 22.6 years. For teeth without periodontal pathologies, the correlation was 0.74 with mean error of 1.6 years. There was correlation of 0.69 between cementum thickness and actual age for the entire sample, 0.25 for teeth with periodontal problems and 0.75 for teeth without periodontal pathologies. The cementum lines technique associated with the measurement of cementum thickness was reliable for teeth without periodontal pathologies, but in periodontally diseased teeth or teeth with unknown history/clinical background, parallel macroscopic examinations should be conducted.

Le terme « cément » est utilisé pour désigner l’ensemble des tissus conjonctifs minéralisés retrouvés sur la surface externe de la racine d’une dent ainsi que sur certaines zones de l’émail ou au niveau du foramen apical. Il appartient à deux unités fonctionnelles : la dent et le parodonte et constitue avec l’os alvéolaire un point d’attache essentiel du ligament alvéolo-dentaire. Dans certaines conditions non encore élucidées la synthèse de l’une de ses variétés, le cément cellulaire mixte stratifié, est excessive, elle dépasse la « normalité » : il s’agit d’une hypercémentose. Une revue critique de la littérature nous a permis de mettre en évidence un certain nombre de problématiques concernant sa définition, sa classification, sa fréquence, ses étiologies et certaines de ses caractéristiques anatomiques. Afin d’y répondre nous avons élaboré un protocole d’étude dont le matériel comprenait trois séries d’Hommes sub-actuels (675 individus ; 8861 dents dont 419 hypercémentosées) et dont les méthodes ont fait appel à la photographie, la radiographie, la stéréomicroscopie, la microscopie électronique à balayage et l’histologie. Au terme de notre étude nous avons mis au point une définition et une classification de l’hypercémentose reposant sur des critères reproductibles, nous avons évalué sa fréquence au sein de grands échantillons et déterminé ses principales étiologies (éruption continue liée à la perte des dents antagonistes, parodontite apicale, atteintes parodontales, inclusion dentaire, pathologies générales, syndromes génétiques, hérédité, idiopathie). Nous avons également fourni certaines données inédites concernant les épaisseurs du cément hyperplasique et l’anatomie des foramens apicaux. Nos résultats ont enfin été appliqué à un certain nombre de dents néandertaliennes ce qui nous a permis de reconsidérer l’hypothèse selon laquelle l’importance des contraintes occlusales au sein de ce taxon est la cause principale des hypercémentoses. / The term "cement" is used to refer to all mineralised connective tissue found on the external surface of the root of a tooth and also on certain areas of the enamel or around the apical foramen. It pertains to two functional units, the tooth and the periodontium, and together with the alveolar bone forms an essential point of attachment for the periodontal ligament. In certain conditions that have still to be clarified, synthesis of one variety of cement, cellular mixed stratified cementum, is excessive, going beyond "normal" levels: this is hypercementosis. From a review of the literature, we identified a certain number of questions relating to the definition, classification, frequency, and etiologies of this term, and also to some of its anatomical characteristics. To find answers to these questions, we set up a study protocol on material consisting of three series of modern Humans (675 individuals; 8,861 teeth, 419 with hypercementosis), using photography, radiography, stereomicroscopy, scanning electron microscopy and histology techniques. From this we were able to produce a definition and a classification of hypercementosis based on reproducible criteria, we assessed frequency using a large set of samples and determined the main etiologies (continuous eruption associated with the loss of opposing teeth, apical periodontitis, periodontal injuries, dental inclusion, general pathologies, genetic syndromes, heredity, idiopathy). We were also able to provide new data on hyperplastic cement thicknesses and the anatomy of apical foramens. Finally, our results were applied to a number of Neanderthal teeth, which led us to reconsider the hypothesis according to which the importance of occlusal stress in this taxon is the main cause of hypercementosis.

Ce travail s'intéresse à l'organisation saisonnière des activités de la fin du Moustérien, avant l'arrivée de l'Homme anatomiquement moderne dans le Sud-Ouest de la France. Il propose une réflexion sur les capacités d'anticipation et de planification des Néandertaliens dans la gestion de leurs ressources animales par l'étude des saisons d'abattage. Pour déterminer la saisonnalité de prédation, l'étude des dépôts de cément dentaire, qui permet l'analyse d'un grand nombre d'individus, a été retenue pour ce travail. Cette thèse propose, dans une optique archéozoologique, de mettre les données saisonnières en perspective avec l'ensemble des informations disponibles portant sur les populations animales chassées. Une revue critique est proposée de la cémentochronologie et des différents biais qui peuvent affecter cette méthode dans la détermination de la saison de mort des animaux en contexte préhistorique. Un protocole d'étude tenant compte, en particulier, des remobilisations post-mortem des structures du cément et traitant des problèmes d'échantillonnage par une approche probabiliste est alors mis en oeuvre. L'analyse archéozoologique et cémentochronologique d'un site d'habitat (Pech de l'Azé I) et l'analyse cémentochronologique d'un possible camp de chasse (La Quina) ainsi que d'un site d'abattage (Mauran) permettent d'aborder différents aspects de la subsistance moustérienne. Les résultats sont comparés à ceux obtenus sur le gisement d'Isturitz, daté du début de l'Aurignacien. Ce travail conclut à l'existence au Moustérien d'économies de subsistance complexes, avec une planification des activités au sein du territoire visible au travers de la spécialisation de certains gisements. La présence d'abattage en masse à la saisonnalité marquée confirme l'existence d'une anticipation dans la gestion des ressources carnée.

Excavated osteological material has been very valuable tool to reconstitute the more precise and objective view of the horses farmed in the past, to follow the evolution of the Lithuanian horse. The data that enabled to estimate the height, constitution and age of the horse is very rare. The metacarpal, metatarsal bones and scull or at least the lower jaw (mandibule) with teeth could be pointed out as the most valuable material. Teeth belong to the best preserved elements of excavations’ material. Such factors as dentition or wear allow determining the animal age. However solitary molars (as they found frequently) do not able to provide this kind of information. Therefore, the methods allowing determining the horse age according to the tooth height and number of cementum rings are very valuable.

The teeth are amongst the most resilient elements of the human skeleton and are thus often utilised in routine forensic investigation involving the identification of unknown remains. The teeth, however, also have other practical forensic applications. Teeth exposed to thermal stress have the potential to not only aid in identification but also in understanding the circumstances surrounding the fire. Previous investigations have drawn conclusions that if a fire flares up suddenly and intensively, the teeth burst and enamel is lost. If the blaze commences gently and burns slowly, then the first observable morphologic change is the colour. The teeth subsequently are difficult to handle, thus changes in teeth can indicate the history of exposure to thermal conditions. Children are twice as likely to become victims of house fire because of an inability to safely evacuate from areas of danger. The literature demonstrates, however, that research on the effects of incineration on teeth is mostly restricted to the permanent teeth. The apparent lack of knowledge on the effects of incineration on deciduous teeth thus necessitates further research in this area. This research project primarily aims at understanding the effect of extreme temperatures on deciduous teeth. It also aims to relate colour changes that occur post heating with fragility to aid in proper handling of samples in a forensic scenario and to determine the possibility of identifying incineration temperature based on tooth condition. The samples analysed composed of 90 deciduous teeth (45 molars and 45 anteriors) extracted as a part of clinical treatment were used for the study. The project involved exposing extracted deciduous teeth to temperatures ranging from 100°C to 1100°C for 30 minutes using a laboratory Gallenkamp oven. Unheated deciduous teeth were used as controls for the project. Post-incineration the teeth were then analysed under a stereomicroscope and SEM for morphological changes. A colorimetric analysis was also undertaken to evaluate the colour changes induced in the primary teeth due to the thermal stress. It was found that it was possible to identify the incineration temperature based on the tooth condition when the colour changes, stereomicroscopic findings and SEM images were utilised collectively. It was also concluded that the thermally induced changes observed in primary teeth occur at lower temperatures in comparison to the permanent teeth. It was also established that post-incineration deciduous teeth are fragile and show a tendency to fragment after minimal exposure to thermal stress as compared to the permanent teeth. Moreover enamel and dentin remained identifiable in primary teeth even after exposure to 1100°C for 30 minutes while cementum lost its structural morphology at 900°C.

Le rachitisme vitamino-résistant hypophosphatémique (RVRH) est une maladie génétique rare causée par des mutations du gène PHEX. La perte de fonction de la protéine PHEX conduit à l’augmentation du FGF23, une hormone circulante qui agit sur le rein et entraîne une perte systémique de phosphate. Le squelette rachitique des patients atteints de RVRH présente des déformations osseuses et une ostéomalacie. La dentine hypominéralisée des patients est à l’origine d’abcès dentaires fréquents, mais le statut parodontal des patients RVRH est mal connu, de même que leur risque de développer une parodontite pouvant aboutir à la perte des dents. La fonction et le substrat de la protéine PHEX ne sont pas identifiés avec exactitude. Il a été montré in vitro que PHEX avait la capacité d’interagir et de dégrader des protéines membres de la famille des SIBLINGs comme MEPE ou OPN, toutes les deux impliquées dans la régulation de la minéralisation des tissus osseux et dentinaires, mais on ne sait pas si in vivo les défauts de minéralisation observés résultent principalement de l’hypophosphatémie systémique ou bien également des effets directs de l’absence de PHEX sur les protéines régulatrices de la minéralisation. L’objectif de cette thèse a consisté à s’intéresser à la physiopathologie du parodonte dans le RVRH ainsi qu’à déterminer quel était l’impact de la mutation de PHEX dans un modèle de biominéralisation humaine où les conditions de concentration en phosphate pouvaient être ajustées et normalisées. Nous avons d’abord analysé le statut parodontal de 34 patients RVRH dans une étude clinique cas-témoins et ainsi montré que les malades dont la supplémentation en phosphate et vitamine D était tardive ou incomplète présentaient une fréquence et une sévérité accrues de maladie parodontale. Le phénotype parodontal du RVRH a alors été étudié sur des échantillons humains et sur le modèle murin du RVRH, la souris HYP. Nous avons réalisé un modèle d’égression dentaire de façon à permettre une apposition du cément cellulaire, ainsi qu’un modèle de résorption et de réparation osseuses parodontales afin de caractériser l’impact du RVRH sur la physiopathologie parodontale. Nos résultats ont montré que le phénotype parodontal et sa physiopathologie étaient très perturbés dans le rachitisme vitamino-résistant hypophosphatémique et chez la souris HYP, nous avons aussi pu mettre en évidence que le rôle pathologique majeur joué par l’ostéopontine dans le tissu osseux au cours du RVRH ne pouvait pas être généralisé aux autres tissus minéralisés du parodonte. De façon à identifier le rôle de PHEX dans la minéralisation matricielle locale indépendamment de la phosphatémie systémique, nous avons ensemencé des matrices de collagène dense avec des cellules primaires humaines issues de patients RVRH comparés à des contrôles que nous avons cultivés pendant 24 jours en conditions ostéogéniques avec des concentrations en phosphate identiques. Nos résultats ont montré que malgré une concentration normale en phosphate, la perte de fonction de la protéine PHEX entraînait une diminution de la quantité et de la qualité de la phase minérale et une accumulation et une dégradation pathologiques de la protéine OPN. Les contributions originales de ce travail de thèse doctorale ont consisté à démontrer sur le plan clinique et biologique la susceptibilité accrue du rachitisme hypophosphatémique lié à l’X quant au risque de développer une maladie parodontale, ainsi qu’à apporter la preuve d’un rôle pathologique de l’absence de PHEX indépendant de la phosphatémie sur des cultures primaires humaines. / X-linked hypophosphatemia (XLH) is a rare X-linked dominant disorder caused by inactivating mutations in the PHEX gene. The impairment of PHEX protein leads to an increase in FGF23, a circulating factor that causes systemic loss of phosphate. The rachitic skeleton of patients with XLH displays short stature and osteomalacia. Dental defects include poorly mineralized dentin and spontaneous dental abscesses. Little is known about the periodontal condition of XLH and if patients are more prone to develop periodontitis, eventually leading to tooth loss. Although the exact function and substrate of PHEX are not known, it has been shown in vitro that PHEX could interact with SIBLING proteins such as MEPE or OPN, both involved in the regulation of bone and dentin mineralization, but it is not yet clear if the defects in the calcified extracellular matrices of XLH are caused by systemic hypophosphatemia only, or also by local consequences of the absence of PHEX. The aim of this doctoral dissertation was to explore the pathobiology of the XLH periodontium and to determine the impact of PHEX deficiency at the local level in a model of human biomineralization where phosphate supply could be adjusted and normalized. We first examined 34 adults with XLH in a case-control study and observed that periodontitis frequency and severity were increased in individuals with late or incomplete supplementation in phosphate and vitamin D analogs. The periodontium was then analyzed in XLH dental roots and further characterized in the Hyp mouse, the murine model of XLH. We performed a model of tooth movement adaptation leading to the formation of cellular cementum and a model of periodontal breakdown and repair to investigate the impact of XLH on the pathobiology of periodontal tissues. Our results showed strongly affected XLH/Hyp periodontal phenotype and impaired pathobiology and suggested that the key role played by OPN in bone could not be generalized to other periodontal mineralized tissues. In order to determine the role of PHEX in local human mineralization, dense collagen gels were seeded with primary human dental pulp cells harvested from XLH patients displaying PHEX mutations and age-matched healthy individuals. Cell-seeded gels were cultured up to 24 days under osteogenic conditions and controlled phosphate medium concentrations. Our results showed that despite normal phosphate concentrations, PHEX deficiency led to decreased quantity and quality of the mineral phase and a pathologic accumulation and processing of OPN. Overall the original contributions of this doctoral dissertation consist in the demonstration of a higher susceptibility of XLH patients to periodontitis and in the evidence of a local effect of PHEX deficiency in the pathologic intrinsic mineralization from XLH osteogenic cells.