La vascularisation joue un rôle important dans la biologie de l’os. Les souris génétiquement modifiées sont devenues le modèle de choix dans ce champ de recherche ; cependant les outils permettant son exploration structurelle (réseau capillaire) et fonctionnelle (perfusion) dans ce modèle animal, demeurent imparfaits. Notre travail a consisté en une adaptation chez la souris de la technique d’histomorphométrie quantitative vasculaire des os longs, fondée sur le remplissage du réseau par du sulfate de baryum, précédemment développée chez le rat. Nous avons, par ailleurs, mis au point une technique reproductible de mesure de la perfusion osseuse dans le tibia en utilisant le Laser Doppler. En termes d’exploration structurelle, et grâce à une imagerie par microtomographie 3D (Synchrotron ou Nano scanner) nous montrons la supériorité du sulfate de baryum sur le Microfil®, (produit associant silicone et plomb) et sa compatibilité avec les colorations histologiques usuelles et les marquages immuno histochimiques de la paroi vasculaire. Nous établissons la reproductibilité de la technique et nous proposons une nomenclature. En termes de perfusion, après avoir optimisé le protocole en limitant les facteurs de variabilité, nous montrons que le Laser Doppler permet de mesurer de façon reproductible une perfusion strictement osseuse dans le tibia de souris. Sous réserve de recourir { des groupes d’animaux de taille suffisante, (n=15), il devient possible de réaliser des comparaisons intergroupes. Ces deux approches combinées et intégrées, menées sur des souris C57BL/6 et 129sv/Cd1 nous ont permis de montrer (1) qu’il n’y a pas de corrélation entre paramètres de perfusion et de densité vasculaire, (2) que lors du vieillissement chez les mâles, la cinétique d’évolution de la vascularisation osseuse diffère selon le fond génétique, et que la perte osseuse n’est pas accompagnée d’une diminution de la perfusion dans ce modèle, (3) que l’ovariectomie (OVX) induit une diminution de la vascularisation et de la perfusion osseuses qui précède la perte osseuse. Enfin, notre étude des effets vasculaires osseux structurels et fonctionnels de la parathormone 1-84 a montré qu’ils dépendent, à l’instar de ses effets sur la masse osseuse, de son mode d’administration, intermittent ou continu et qu’ils ne sont pas impactés par l’OVX / Vascularisation plays a major role in bone biology. Genetically modified mice became the most favorite model in this research field; however, the tools allowing bone vessel analysis on both structural (capillary network) and functional aspects (perfusion) in this animal model remain unsatisfactory. Our work consisted in adapting in mice the quantitative histomorphometry technique allowing the analysis of long bone vascularization, based on the infusion of barium sulfate, which was previously developed in the rat. In addition, we set up a reproducible Laser Doppler-Based technique for measurement of mouse tibia perfusion. In terms of structural analyses, and thank to 3D micro-Tomography imaging (Synchrotron or Nano scanner), we show the superiority of barium sulfate on a lead/silicon-Based contrast product (Microfil®)and its compatibility with common staining used in histology and with immuno-Histochemsitry of the vessel wall. We establish the reproducibility of the technique and propose a nomenclature. In terms of perfusion, we show, after having optimized the protocol by limiting the factors of variability, that Laser Doppler allows to measure, in a reproducible way, perfusion signals specific to bone. As long as the animal group size is appropriate (n=15), it becomes possible to carry out intergroup comparisons. These combined and integrated approaches, carried out on C57BL/6 and 129sv/Cd1 mice allowed us to show that (1) there is no correlation between perfusion and vascular density parameters (2) during ageing in males, the kinetics of bone vascularisation evolution differ according to the genetic background and that bone loss was not associated with decrease in perfusion in this model (3) that ovariectomy (OVX) induces a decrease in both bone vessel density and perfusion which precedes bone loss. Finally, we studied the structural and functional vascular effects of 1-84 parathyroid hormone and show that, as for its effects on bone mass, they depend on its mode of administration, intermittent or continuous and that they are not affected by OVX

Orientador: Pedro Paulo Chaves de Souza / Resumo: A periodontite é resultado do desequilíbrio entre o biofilme bacteriano e a resposta imune do hospedeiro. Componentes bacterianos, como o lipopolissacarídeo (LPS) e as lipoproteínas, são reconhecidos pelo sistema imune e desencadeiam a produção de citocinas que auxiliam no combate à infecção, mas também induzem a destruição tecidual. A participação do LPS na destruição óssea já é bem estabelecida, porém o papel das lipoproteínas na periodontite permanece carente de investigação. Na periodontite, citocinas pró-inflamatórias participam do processo de destruição do tecido ósseo. Neste processo, são secretadas também citocinas osteoprotetoras. Dentre elas, a interleucina 4 (IL-4) é reconhecida pela propriedade de inibir a produção citocinas pró inflamatórias como IL-1, IL-6 e TNF-α. O papel protetor de IL-4 na osteoclastogênese e na doença periodontal induzida por lipoproteína ainda não foi investigado. Nosso estudo foi divido em dois capítulos. No capítulo 1, hipotetizamos que a lipoproteína sintética Pam2CSK4 (PAM2) poderia induzir a reabsorção óssea periodontal. Para isso, foram utilizados camundongos C57bl/6, que receberam injeções a cada 2 dias, por 24 dias, do veículo, LPS de Escherichia. coli ou PAM2, entre o primeiro e segundo molar superior. Após o período experimental, os animais foram eutanasiados e destinados à análise por microCT, análise histológica e imunohistoquímica para marcação dos osteoclastos. A PAM2 apresentou a capacidade de induzir a perda óssea alveolar, ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The pathogenesis of periodontitis is a result of imbalance between the bacterial biofilm and the host immune response. Bacterial components such as lipopolysaccharide (LPS) and lipoproteins, activate the immune system leading to periodontal distruction. The participation of LPS in periodontal bone destruction is well established, but there is a lack of information about the role of lipoproteins in periodontitis. In the pathogenesis of periodontitis, these molecular patterns are recognized by host immune system and trigger the production of cytokines that participate of antimicrobial response, but also induce tissue destruction. On the other hand, antinflamatory cytokines produced by Th2 cells, such as IL-4, have an osteoprotective phenotype. The role of IL-4 in lipoprotein-induced periodontitis was not yet investigated. Thus, this thesis was divided in two chapters. In chapter 1, we investigated the role of lipoproteins in the pathogenesis of periodontitis in mice. In this study, we hypothesized that the synthetic lipoprotein Pam2CSK4 (PAM2) can induce periodontal bone resorption. C57bl / 6 mice received bilateral injections every other day for 24 days of: vehicle, Escherichia coli LPS or PAM2, between the first and second upper molars. Twenty-four hours after the last injection, the mice were euthanized and the jaw bones were scanned for micro computed tomography, decalcified and processed for histological analysis and stained for tartrate-resistant acid phosphatase, phenoty... (Complete abstract click electronic access below) / Doutor

Objetivos: Avaliar o efeito da inibição de triptase, com o uso da droga nafamostate mesilate (NM), sobre o desenvolvimento de doença periodontal induzida em ratos. Metodologia: Oitenta ratos Wistar machos foram divididos aleatoriamente em quatro grupos. Um grupo controle com injeção diária de NaCl 0,9%, grupo NM (injeção diária de 0.1mg/kg de NM, ip), grupo ligadura (colocada ao redor do primeiro molar inferior direito), e grupo NM + Ligadura. A quantidade de perda óssea alveolar (POA) na porção mesial da face lingual da raiz mésio-lingual do primeiro molar inferior foi determinada após o sacrifício aos sete e 14 dias com o auxílio de um estereomicroscópio, e a atividade de mieloperoxidase (MPO) foi analisada nos tecidos gengivais. Resultados: A inibição da triptase levou à diminuição significativa (p <0,05) de POA em animais submetidos à ligadura e periodontite induzida. A inibição da triptase pelo NM não apenas preveniu o início da POA aos sete dias de experimento (0,44mm 0,16 e 0,60mm 0,22, p<0,05, NM + Ligadura versus Controle), como também diminuiu significativamente a POA aos 14 dias (0,97mm 0,17 versus 1,82mm 0,26, p <0,001, NM + Ligadura versus Ligadura). Além disso, a inibição da triptase diminuiu significativamente a atividade de MPO aos 14 dias (p<0.05). Conclusão: Os dados do presente estudo sugerem que a inibição da triptase modificou a progressão da periodontite induzida experimentalmente em ratos. / Aim: To evaluate the effect of inhibition of tryptase, with the drug nafamostate mesylate (NM) on the development of periodontal disease induced in rats. Methodology: Eighty (80) male Wistar rats were randomly separated into four study groups as follows: saline Control group, NM group (daily injection of 0.1mg/kg body weight of NM, i.p.), Ligature group (ligature placed at the gingival margin level of lower right first molars), and NM + Ligature group. The amount of alveolar bone loss (ABL) around the mesial root surface of the first mandibulary molar was determined at sacrifice at seven and 14 days with the aid of a stereomicroscope, and the myeloperoxidase activity (MPO) was analyzed at the gingival tissues. Results: NM led to significantly (p<0.05) decreased ABL in animals subjected to ligature induced periodontitis. Tryptase inhibition not only prevented the onset of significant ABL at seven days of the experiment (0.440.16 and 0.600.22, p>0.05, NM+Ligature and Control, respectively) but also significantly decreased the ABL when compared with the Ligature group at 14 days (0.970.17 versus 1.820.26, p<0.001). In addition, NM significantly decreased MPO activity at 14 days (p<0.05). Conclusion: These data provide evidence that tryptase inhibition may modify the progression of experimentally induced periodontitis in rats.

<div>Osteoporosis is the most common bone disease in older adults and is characterized by low bone mass and increased fragility. Women are at a higher risk for osteoporosis because of the rapid loss of bone during menopause. The decline of estrogen is accompanied by an increased bone resorption and a decreased bone formation which results in negative bone balance. Due to adverse effects on the uterus, breast and cardiovascular system, hormone replacement therapy has been discouraged. Nutritional strategies for osteoporosis prevention are being sought. It has been suggested that (poly)phenol-rich fruits may have bone protective effects. Blueberries are one of the richest sources of (poly)phenols, thus the aim of this dissertation was to determine whether a blueberry-enriched diet could aid in bone loss prevention in the ovariectomized rat model.</div><div><br></div><div>There are hundreds of blueberry varieties which differ in (poly)phenol profiles and content. Five blueberry varieties (Ira, Montgomery, SHF2B1-21:3, Onslow and Wild Blueberry) were chosen to assess the bioavailability of its individual (poly)phenols. Bioavailability of individual phenolic metabolites was determined through a pharmacokinetic study in ovariectomized rats. The results showed that Montgomery blueberry had significantly higher bioavailability of malvidin, cyanidin and myricetin metabolites, while Ira had significantly higher bioavailability of quercetin metabolites, thus suggesting that the absorption of blueberry polyphenols and their potential to reach target tissues differed between blueberry varieties.</div><div><br></div><div>It is important to assess what is the most appropriate dose of blueberry necessary to exert beneficial effects on bone. To determine the most adequate dose of wild blueberry to prevent bone loss in ovariectomized rats, a randomized crossover study was carried out to assess the effects of four different blueberry doses on net bone calcium retention over a 10-day treatment period. The results showed that the only dose to significantly increase net bone calcium retention by 25.6% (p = 0.0426) was the 5% blueberry diet (% w/w), while the higher doses of 10% and 15% had no effect on net bone calcium retention. This informed the last study where Montgomery blueberry and wild blueberry at a 5% dose (% w/w) were chosen to investigate the effects of an 8-week chronic feeding study on calcium metabolism, kinetics, bone microarchitecture and strength and polyphenol metabolism and distribution. A chronic consumption of the wild blueberry resulted in a trend towards minimal trabecular bone loss protection in comparison to the control diet (p=0.08). Kinetic modeling of calcium showed that the Montgomery blueberry had anabolic effects on bone through significantly increasing calcium absorption and bone deposition. The phenolic metabolism differed among blueberry varieties due to each berry’s polyphenol content and profiles and a chronic consumption of blueberry resulted in significant changes in absorption and metabolism of polyphenols. The bone marrow was investigated to determine whether there was any accumulation of phenolic acids in the tissue. Hippuric acid accumulation was significantly higher with the Montgomery blueberry treatments in comparison to control diet. Interestingly, hippuric acid content in the bone marrow was significantly and positively correlated with bone deposition calculated from kinetic modeling. Although no differences were observed on bone mineral density, strength, and microarchitecture, previous studies with a duration of 12-14 weeks have shown significant protection of a blueberry-enriched diet on bone mineral density. Because our study showed a trend for increased trabecular bone (p = 0.08) with the blueberry treatments, we conclude that an 8-week treatment was insufficient time to detect significant differences between the control and blueberry treatments. Since previous researchers before us have reported significant attenuation to bone loss immediately after OVX, it is possible that blueberry that in our study, blueberry was unable to rescue bone once lost after ovariectomy.<br></div><div><br></div><div>A blueberry-enriched diet resulted in a minimal protection to bone after stabilized to OVX, but showed significant increases in calcium absorption and bone turnover in ovariectomized rats. Colonic metabolite profiles from the chronic consumption of blueberry significantly changed over time, thus providing an insight into the effects of blueberry consumption on polyphenol metabolism.<br></div><div><br></div>

Einleitung Bei Zahnverlust ist das Setzen eines Implantates eine gängige und etablierte Behandlungsmethode. Zahnimplantate bieten für den Patienten viele Vorteile. Im Vergleich zum Einsatz einer klassischen Brücke müssen keine Nachbarzähne beschliffen werden. Gesunde Zahnsubstanz bleibt erhalten. Der künstliche Zahn sitzt fest und sicher im Kiefer und bietet Schutz vor Knochenverlust. Ein Implantat leitet die beim Kauen entstehenden Kräfte gleichmäßig in den Kieferknochen. Ein weiterer Vorteil ist die Sicherstellung der natürlichen Funktionen wie Kauen, Sprechen oder Lachen. Somit trägt implantatgetragener Zahnersatz erheblich zur Verbesserung der Lebensqualität bei. Zur Planung des chirurgischen Eingriffs und dem eigentlichen Setzen des Implantates sind die Zahnärzte und Zahntechniker auf Softwarelösungen angewiesen, welche nicht nur die Möglichkeit der Befundung, Analyse und Diagnostik bieten, sondern gleichermaßen die Informationen liefern, die erforderlich sind, um mit Hilfe eines Computers die Fertigung einer Bohrschablone zu planen (CAM-System) und mittels CNC-Fertigung herzustellen.

Hormone ablation therapy is a mainstay in the treatment of breast and prostate cancers. However, aromatase inhibitors (AIs) used in postmenopausal women with breast cancer and androgen-deprivation therapy (ADT) used in men with prostate cancer contribute to substantial bone loss, thereby increasing the risk of osteoporotic fractures. Evidence-based guidelines, therefore, urge oncology practices to screen these patients for bone loss and, if needed, provide treatment to maintain bone health. In addition to lifestyle modification and calcium or vitamin D supplementation, bone protection strategies include treatment with bisphosphonates and denosumab, a monoclonal antibody against RANK ligand. Identification of patients at greater risk for bone loss and fracture and proper interventions can reduce fracture rates. Oncology nurses can play an important role in screening these patients. The purpose of this article is to inform oncology nurses about the effects of cancer treatment on bone health, review current prevention and treatment options for cancer treatment-induced bone loss, and discuss recommendations for identifying high-risk individuals.

Abstract  Objective:The aim of this retrospective study was to examine the influence of a cantilever on marginal bone loss (MBL) around dental implants supporting 3-unit partial fixed prostheses.  Materials and methods:Retrospective data were collected from dental records of patients at a specialist clinic in Malmö, Sweden, covering the period from 1980 to 2018. Only implants not lost and with baseline radiographs taken within 12 months after implant placement and with a minimum of 36 months of radiological follow-up were considered for the analysis of MBL. Univariate linear regression models and a final linear mixed-effects model were used to analyze the results.  Results:139 patients (64 men and 75 women) were included in our study, with 161 implant- supported FDPs undergoing radiological follow-up over at least 36 months. These patients had 428 implants (95 and 333 implants supporting prostheses with and without cantilever, respectively). Total number of double measurements for marginal bone level was 2,909, including 2,238 without cantilever and 671 with cantilever. There was a significant relationship between MBL over time the presence of cantilever, patient’s sex, implant surface, bone quality of the implant site, and bruxism.  Conclusion: MBL around dental implants supporting 3-unit partial fixed prostheses over time was significantly influenced by cantilever.  Keywords: Implant-supported fixed partial prosthesis, cantilever, marginal bone loss / Sammanfattning  Syfte: Syftet med den föreliggande retrospektiva studien var att undersöka inverkan av en kantilverburen protetisk arm på marginal benförlust runt tandimplantat som stödjer korta partiella fasta proteser. Material och metod:Det fanns 139 patienter med i vår studiegrupp (64 män och 75 kvinnor) med 161 implantatstödda FDPs som hade en röntgenologisk uppföljning under minst 36 månader. Den beskrivande datan om fallen baserades på data som samlats in från patienternas journaler gällande ålder och andra faktorer som analyserades. Studien baseras på data som samlats in från patienternas journaler mellan 1980 och 2018 på en specialistklinik i Malmö, Sverige där röntgenbilder har analyserats för att mäta benförlust runt implantat. Statistiska analyser har utförts för att utvärdera resultaten i förhållande till kantilever samt olika patientfaktorer. Resultat:Den totala mängden dubbelmättningar för marginala bennivån var 2909 st, där 2238 st var utan kantilever och 671 var med kantilever. Genom vårt resultat kunde man se ett signifikant samband mellan förlust av marginalt ben (MBL) och flera faktorer, såsom kantileverburen arm, kön, implantatyta, benkvalitet och bruxism. Slutsats: MBL runt 3-unit implantat-

Aim: The overall aim is to (i) analyze the prognosis of dental implant treatment concerning marginal bone loss (MBL) in patients undergoing or have undergone treatment with bone antiresorptive or antiangiogenic medication for osteoporosis (ii) and additional purpose to assess the available scientific literature in the first aim concerning the risk of getting medication-related osteonecrosis of the jaw (MRONJ) associated with dental implant installation.  Material and methods: A systematic literature search was conducted in October 2021 in the following three databases; MEDLINE/PubMed, Cochrane Library and Web of Science. PRISMA 2009 Flow Diagram were used for the selection process, whereas the included studies were evaluated for quality assessment using Newcastle Ottawa Scale (NOS).  Results: The search resulted in four included studies considering the eligibility criteria. The studies evaluated MBL in osteoporotic patients undergoing or have undergone oral bisphosphonate (BP) treatment before and/or during implant placement. MRONJ was also assessed in all four articles.  Conclusions: The results of this present study do not indicate that patients undergoing or have undergone antiresorptive or antiangiogenic medication for osteoporosis are at an increased risk of MBL in dental implants during follow-up periods. The present data assessing the risk for developing MRONJ remains low for osteoporotic patients. Therefore, dental implant surgery is considered possible with success in osteoporotic patients receiving earlier mentioned medications. However additional studies are required to evaluate the effects on this patient group concerning osseointegration of dental implant regarding MBL. / Syfte: Syftet med denna studie är att analysera prognosen för implantatbehandling avseende marginell benförlust (MBL) hos patienter som genomgår eller har genomgått behandling med benantiresorptiv eller antiangiogen medicin för osteoporos. Ytterligare utförs en bedömning av tillgänglig vetenskaplig litteratur gällande risken för läkemedelsrelaterad käkbensnekros (MRONJ) associerat med implantatinstallation hos patienter som genomgår eller har genomgått behandling med benantiresorptiv eller antiangiogen medicin. Material och metod: En systematisk elektronisk litteratursökning genomfördes i oktober 2021 i följande tre databaser; MEDLINE/PubMed, Cochrane Library och Web of Science. PRISMA 2009 Flow Diagram användes för urvalsprocessen, varav de inkluderande studierna kvalitetsgranskades enligt Newcastle Ottawa Scale (NOS). Resultat: Sökningen resulterade i fyra studier, enligt inklusions- och exklusionskriterier. Studierna utvärderade MBL hos osteoporospatienter som går eller har gått behandling med orala bisfosfonater före eller under implantatinstallationen. MRONJ fastställdes i alla fyra artiklar. Slutsats: Resultatet av denna studie indikerar inte att patienter som genomgår eller har genomgått behandling med benantiresorptiv eller antiangiogen medicin för osteoporos löper en ökad risk för MBL av dentala implantat under uppföljningsperioder. Nuvarande data bedömer att risken för att utveckla MRONJ är fortfarande låg för osteoporos patienter. Därför antas implantatkirurgi kunna utföras på osteoporos patienter som står på denna medicinering. Dock krävs ytterligare studier för att utvärdera effekterna av denna patientgrupp gällande osseointegration av dentala implantat avseende MBL.

AIM: To evaluate marginal bone loss around dental implants at the 2nd stage abutment surgery and retrospectively evaluate the association of pre-surgical variables. MATERIAL AND METHODS: Eighty-seven subjects (41 Males and 46 females) were enrolled in this cohort. The subjects' ages ranged from 23 to 80 years. Two endosseous implant brands were utilized: Nobel Biocare and Straumann Bone Level . Clinical measurements (mesial, distal, buccal, and lingual) were recorded from the coronal margin of the implant platform to the bone margin with a periodontal probe (Williams periodontal probe, Hu-Friedy) at the time of implant placement and at the 2nd stage abutment surgery. The pre-surgical variables (medication intake, implant site, bone graft volume, membrane type, and smoking) were evaluated using Chi-square test. RESULTS: The marginal bone loss (MBL) difference was calculated. The Mean clinical MBL: Mesial = 0.71 mm, Distal = 0.56mm, Buccal/Labial = 0.65 mm, and Lingual/Palatal = 0.56 mm. The test showed no statistically significant difference between test and control subjects in each of the variables, with the exception of thyroid medication. A statistically significant (P value = 0.011) association was found between levothyroxine and MBL at the mesial measurement. CONCLUSION: This limited cohort study suggests that medication-controlled hypothyroidism patients may experience an increased risk of marginal alveolar bone loss around dental implants at the 2nd stage abutment surgery. The final determination will be recalculated when the study population reaches the estimated requirement of 200 subjects.

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