The Role of Apical Periodontitis Disease in the Development of Bisphosphonate-Related Osteonecrosis of the Jaw: An Animal Study.

BACKGROUND: Microorganisms and their by-products are responsible for establishing pulpal and periapical diseases. Healing is compromised in patients under bisphosphonate therapy, and the presence of periapical infections can potentially lead to the development of medication-related osteonecrosis of the jaw (MRONJ). This work aimed to evaluate if bisphosphonate therapy is a risk factor for MRONJ development in the presence of periapical lesions. METHODS: Two groups of 10 female Wistar rats were used. The experimental group received zoledronate (0.1 mg/kg) intraperitoneally, and the control received a saline solution, three times a week for three weeks. One week after the last injection, apical periodontitis was induced through pulpal exposure in the mandibular first molars. Twenty-one days later, the animals were intravenously injected with 99mTc-HMDP, and the radioactivity uptake by mandibular specimens was counted. In addition, sample radiographs and a histological examination were performed. RESULTS: The bone loss was higher in the control group when compared to the experimental group (p = 0.027). 99mTc-HMDP uptake in the control was reduced compared with the experimental group, although without statistical significance. CONCLUSIONS: In the presence of zoledronate therapy, apical periodontitis does not increase the risk of MRONJ development, and periapical lesions have lower bone resorption when compared to the control group.

Microleakage Evaluation of Temporary Restorations Used in Endodontic Treatment-An Ex Vivo Study.

(1) Background: Coronal microleakage can lead to endodontic treatment failure. This study aimed to compare the sealing ability of different temporary restorative materials used during endodontic treatment. (2) Methods: Eighty sheep incisors were collected, uniformized in length, and access cavities were performed, except for in the negative control group, where the teeth were left intact. The teeth were divided into six different groups. In the positive control group, the access cavity was made and left empty. In the experimental groups, access cavities were restored with three different temporary materials (IRM®, Ketac™ Silver, and Cavit™) and with a definitive restorative material (Filtek Supreme™). The teeth were submitted to thermocycling, and two and four weeks later, they were infiltrated with 99mTcNaO4, and nuclear medicine imaging was performed. (3) Results: Filtek Supreme™ obtained the lowest infiltration values. Regarding the temporary materials, at two weeks, Ketac™ Silver presented the lowest infiltration, followed by IRM®, whereas Cavit™ presented the highest infiltration. At four weeks, Ketac™ Silver remained with the lowest values, whereas Cavit™ decreased the infiltration, comparable to IRM®. (4) Conclusion: Regarding temporary materials, Ketac™ Silver had the lowest infiltration at 2 and 4 weeks, whereas the highest infiltration was found in the Cavit™ group at two weeks and in the IRM® group at 4 weeks.

Evaluation of the Sealing Ability and Bond Strength of Two Endodontic Root Canal Sealers: An In Vitro Study.

BACKGROUND: Obturation represents a critical step in endodontic treatment, which relies on a core material and a sealer. This study aims to evaluate the sealing ability and bond strength to the root canal walls of an epoxy resin-based sealer (AH-Plus®, Dentsply Sirona, Johnson City, TN, USA) and a bioceramic sealer (GuttaFlow Bioseal®, Coltène/Whaledent, GmbH + Co. KG, Langenau, Germany). METHODS: Thirty-eight maxillary anterior teeth with single roots and identical round sections were separated into two experimental groups according to the root canal sealers used, namely, G1 = AH-Plus® and G2 = GuttaFlow Bioseal®, and two control groups, specifically, G3 = the negative control and G4 = the positive control. The sealing capacity was measured by the penetration of the radioactive isotope 99mTc. For the push-out test, the compressive force test was performed in a universal machine and the force was applied by exerting pressure on the surface of the material to be tested in the apical to the coronal direction and using three test points with different diameters. RESULTS: GuttaFlow Bioseal® exhibited superior sealing ability compared to AH-Plus® (p = 0.003). Regarding the bond strength, AH-Plus® provided higher adhesion values than GuttaFlow Bioseal® in the three sections of the tooth root (p = 0.001). CONCLUSIONS: GuttaFlow Bioseal® had significantly better sealing ability than AH-Plus® but lower adhesion values in the three zones of the root canal, with statistically significant differences between the groups. However, it is important to note that for the action of endodontic sealers to be maximized, the root-filling technique must be most appropriate.

Apical Sealing Ability of Two Calcium Silicate-Based Sealers Using a Radioactive Isotope Method: An In Vitro Apexification Model.

The aim of this study was to evaluate and compare the sealing ability of two calcium silicate-based sealers (TotalFill BC RRM Fast Set Putty and White ProRoot MTA) when used as apical plugs in immature teeth through nuclear medicine. Single-rooted extracted teeth (n = 34) had their crowns and root tip sectioned to obtain 14 mm long root segments to simulate an in vitro apexification model. Were created two experimental groups, namely MTA (n = 12) and BC (n = 12), and two control groups, PG (positive group, n = 5) and NG (negative group, n = 5). On the 4th day after placing the respective apical plug, the apical portions of the teeth were submerged in a solution of sodium pertechnetate (99mTcNaO4) for 3 h. Statistical analysis showed a significant difference between the MTA group and the controls (p < 0.05). The BC group had a significant difference regarding the negative control (p < 0.001) but showed no statistical significance regarding the positive control (p = 0.168). There was a statistically significant difference (p = 0.009) between the BC group (7335.8 ± 2755.5) and the MTA group (4059.1 ± 1231.1), where the last showed less infiltration. Within the limitations of this study, White ProRoot MTA had a significantly better sealing ability than TotalFill BC RRM Fast Set Putty.

Impairment of the angiogenic process may contribute to lower success rate of root canal treatments in diabetes mellitus.

AIM: To investigate the association between root canal treatment outcome, diabetes mellitus, and alterations of the angiogenic process. METHODOLOGY: A retrospective observational study was conducted in healthy (control group, CG) and diabetic (type II diabetes mellitus group, DG) patients after root canal treatment. The follow-up appointments were performed to clinically and radiographically observe symptoms, the healing of periapical lesions and the quality of root fillings. In the animal model study, diabetic Goto-Kakizaki (GK) rats and control Wistar rats were used. After 21 days of pulp exposure and the development of apical periodontitis (AP), the mandibles were removed for scintigraphic, radiographic, histopathological and molecular analyses. Chi-square tests were performed to examine the variables related to endodontic outcome and differences between animal groups were assessed using the Student's t-test. RESULTS: The group of patients with diabetes had a significantly lower rate of success following root canal treatment than the CG (p < .001). Logistic regression suggested that diabetes is a risk factor for success of root canal treatment. In the animal study, GK rats had significantly higher fasting glycaemia at t0 and t21 (p < .001) and triglycerides levels (p < .05) and area under the curve (AUC) during the insulin tolerance test at t21 (p < .001). AP area was significantly greater in GK rats (p < .05). Histologically, diabetic rats had increased signs of periodontal ligament inflammation 21 days after the induction of apical periodontitis, with fibro-hyaline matrix filling and vessel with undefined walls. Wistar rats had significantly increased vascular endothelial growth factor (VEGF) levels and VEGF/Ang-2 ratio 21 days after AP induction (p < .08; p < .07). GK rats had intrinsically lower levels of VEGF than control rats (p < .05), which did not change after AP. CONCLUSION: Diabetes mellitus should be considered as an important factor in the prognosis of root canal treatment and its outcomes over time. Future strategies to improve angiogenesis and tissue repair should be pursued to achieve better root canal treatment outcomes in diabetic patients.

Effect of Different Irrigation Solutions on the Diffusion of MTA Cement into the Root Canal Dentin.

(1) Aim: This study aims to analyze the in vitro infiltration of a silicate root canal sealer into dentinal tubules after using different endodontic irrigating solutions. (2) Methods: Twenty-nine teeth with single roots were separated into three groups according to the final irrigation protocol: G1 n = 10) = 17% EDTA (ethylenediaminetetraacetic acid) + 3.0% sodium hypochlorite (NaOCl), G2 (n = 10) = 17% EDTA + 2.0% chlorhexidine and G3 (Control group, n = 9) = 17% EDTA + saline solution. Root canals were filled using cold lateral compaction technique with MTA Fillapex sealer and gutta-percha. The sealer was labeled with rhodamine B. The teeth were segmented at the middle and third apical sections, which were visualized using 10× confocal laser microscopy to determine the sealer penetration percentage. (3) Results: In the apical section, no statistically significant differences were found between the groups regarding sealer penetration. In the middle section, Group 1 obtained the highest percentage, and Group 2 the lowest (p = 0.004). Group 1 also presented statistically significant differences in the Control Group (p = 0.031) and had close sealer penetration values. Meanwhile, the Control Group (p = 0.023) and Group 2 (p = 0.029) revealed a significant decrease of sealer penetration between the apical and middle sections. (4) Conclusion: The obtained results support that final irrigation with NaOCl promoted similar sealer penetration in the apical and middle sections. On the other hand, a significant decrease in the sealer penetration of the middle section was observed for the chlorhexidine and saline groups. Compared to other irrigant solutions, NaOCl promotes more uniform sealer penetration, which can correlate with better sealing and, consequently, higher endodontic treatment success.

Calcium Phosphate Ceramics Can Prevent Bisphosphonate-Related Osteonecrosis of the Jaw.

Bisphosphonate-associated osteonecrosis of the jaw (BRONJ), a post-surgical non-healing wound condition, is one of the most common side effects in patients treated with nitrogen-containing bisphosphonates. Its physiopathology has been related with suppression of bone turnover, of soft tissue healing and infection. Biphasic calcium phosphates (BCP) are used as a drug delivery vehicle and as a bone substitute in surgical wounds. Due to their capacity to adsorb zoledronate, it was hypothesized these compounds might have a protective effect on the soft tissues in BRONJ wounds. To address this hypothesis, a reproducible in vivo model of BRONJ in Wistar rats was used. This model directly relates chronic bisphosphonate administration with the development of osteonecrosis of the jaw after tooth extraction. BCP granules were placed in the alveolus immediately after tooth extraction in the test group. The animals were evaluated through nuclear medicine, radiology, macroscopic observation, and histologic analysis. Encouragingly, calcium phosphate ceramics were able to limit zoledronate toxicity in vivo and to favor healing, which was evidenced by medical imaging (nuclear medicine and radiology), macroscopically, and through histology. The studied therapeutic option presented itself as a potential solution to prevent the development of maxillary osteonecrosis.

Cytotoxic effects of a chlorhexidine mouthwash and of an enzymatic mouthwash on human gingival fibroblasts.

The aim of this study was to evaluate the cytotoxic effects of an enzymatic mouthwash and of a chlorhexidine mouthwash on human gingival fibroblasts. The metabolic activity of the fibroblasts exposed to each mouthwash was assessed by the MTT assay and the protein content was assessed by the SRB assay. The flow cytometry was used to evaluate the cell cycle and the types of cell death. The oxidative status was evaluated through the DCF and the DHE probes and the intracellular GSH concentration and the mitochondrial membrane potential through JC-1. The cytotoxicity of both mouthwashes was found to be dependent on the exposure time and on the concentration. However, the cytotoxicity of the enzymatic mouthwash was found to be lower than that of the chlorhexidine mouthwash. A trend towards increased oxidative stress was observed for both mouthwashes. After exposing the fibroblasts to the mouthwashes, a G2/M phase block was observed and cell death occurred predominantly by necrosis. The effects of chlorhexidine on fibroblasts were identified at lower concentrations than those used in clinical practice. Therefore, the use of chlorhexidine as an antiseptic in surgical and postoperative situations should be limited. In order to clarify the clinical significance of the enzymatic mouthwash cytotoxicity new clinical studies will be necessary.

Evaluation of dentinogenesis inducer biomaterials: an in vivo study.

When exposure of the pulp to external environment occurs, reparative dentinogenesis can be induced by direct pulp capping to maintain pulp tissue vitality and function. These clinical situations require the use of materials that induce dentin repair and, subsequently, formation of a mineralized tissue. OBJECTIVE: This work aims to assess the effect of tricalcium silicate cements and mineral trioxide aggregate cements, including repairing dentin formation and inflammatory reactions over time after pulp exposure in Wistar rats. METHODOLOGY: These two biomaterials were compared with positive control groups (open cavity with pulp tissue exposure) and negative control groups (no intervention). The evaluations were performed in three stages; three, seven and twenty-one days, and consisted of an imaging (nuclear medicine) and histological evaluation (H&E staining, immunohistochemistry and Alizarin Red S). RESULTS: The therapeutic effect of these biomaterials was confirmed. Nuclear medicine evaluation demonstrated that the uptake of 99mTc-Hydroxymethylene diphosphonate (HMDP) showed no significant differences between the different experimental groups and the control, revealing the non-occurrence of differences in the phosphocalcium metabolism. The histological study demonstrated that in mineral trioxide aggregate therapies, the presence of moderate inflammatory infiltration was found after three days, decreasing during follow-ups. The formation of mineralized tissue was only verified at 21 days of follow-up. The tricalcium silicate therapies demonstrated the presence of a slight inflammatory infiltration on the third day, increasing throughout the follow-up. The formation of mineralized tissue was observed in the seventh follow-up day, increasing over time. CONCLUSIONS: The mineral trioxide aggregate (WhiteProRoot®MTA) and tricalcium silicate (Biodentine™) present slight and reversible inflammatory signs in the pulp tissue, with the formation of mineralized tissue. However, the exacerbated induction of mineralized tissue formation with the tricalcium silicate biomaterial may lead to the formation of pulp calcifications.

Evaluation of dentinogenesis inducer biomaterials: an in vivo study

Abstract When exposure of the pulp to external environment occurs, reparative dentinogenesis can be induced by direct pulp capping to maintain pulp tissue vitality and function. These clinical situations require the use of materials that induce dentin repair and, subsequently, formation of a mineralized tissue. Objective: This work aims to assess the effect of tricalcium silicate cements and mineral trioxide aggregate cements, including repairing dentin formation and inflammatory reactions over time after pulp exposure in Wistar rats. Methodology: These two biomaterials were compared with positive control groups (open cavity with pulp tissue exposure) and negative control groups (no intervention). The evaluations were performed in three stages; three, seven and twenty-one days, and consisted of an imaging (nuclear medicine) and histological evaluation (H&E staining, immunohistochemistry and Alizarin Red S). Results: The therapeutic effect of these biomaterials was confirmed. Nuclear medicine evaluation demonstrated that the uptake of 99mTc-Hydroxymethylene diphosphonate (HMDP) showed no significant differences between the different experimental groups and the control, revealing the non-occurrence of differences in the phosphocalcium metabolism. The histological study demonstrated that in mineral trioxide aggregate therapies, the presence of moderate inflammatory infiltration was found after three days, decreasing during follow-ups. The formation of mineralized tissue was only verified at 21 days of follow-up. The tricalcium silicate therapies demonstrated the presence of a slight inflammatory infiltration on the third day, increasing throughout the follow-up. The formation of mineralized tissue was observed in the seventh follow-up day, increasing over time. Conclusions: The mineral trioxide aggregate (WhiteProRoot®MTA) and tricalcium silicate (Biodentine™) present slight and reversible inflammatory signs in the pulp tissue, with the formation of mineralized tissue. However, the exacerbated induction of mineralized tissue formation with the tricalcium silicate biomaterial may lead to the formation of pulp calcifications

Biocompatibility of Root Canal Sealers: A Systematic Review of In Vitro and In Vivo Studies.

(1) Aim: To perform a systematic review of the literature on the biocompatibility of root canal sealers that encompasses the various types of sealers that are commercially available as well as both in vitro and in vivo evidence. (2) Methods: This systematic review has been registered in PROSPERO (ID 140445) and was carried out according to PRISMA guidelines using the following databases: PubMed, Cochrane Library, ClinicalTrials.gov, Science Direct, and Web of Science Core Collection. Studies published between 2000 and 11 June 2019 that evaluated cytotoxicity (cell viability/proliferation) and biocompatibility (tissue response) of root canal sealers were included. (3) Results: From a total of 1249 studies, 73 in vitro and 21 in vivo studies were included. In general, studies suggest that root canal sealers elicit mild to severe toxic effects and that several factors may influence biocompatibility, e.g., material setting condition and time, material concentration, and type of exposure. Bioactive endodontic sealers seem to exhibit a lower toxic potential in vitro. (4) Conclusions: The available evidence shows that root canal sealers exhibit variable toxic potential at the cellular and tissue level. However, the methodological heterogeneity among studies included in this systematic review and the somewhat conflicting results do not allow a conclusion on which type of sealer presents higher biocompatibility. Further research is crucial to achieve a better understanding of the biological effects of root canal sealers.

Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw.

(1) Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the most often seen side effects in patients treated with nitrogen-containing bisphosphonates (BPs), a post-surgical non-healing wound condition. Since calcium phosphate (CP) compounds are able to adsorb zoledronate (ZOL) when used as a drug delivery vehicle, we aimed to verify if these ceramics might have a potential protective effect for soft tissues surrounding surgical osseous wounds. (2) Methods: The chemical reaction between ZOL and CP compounds was evaluated through ultraviolet-visible spectroscopy and elemental analysis. A primary culture of human gingival fibroblasts (HGF) was established as a model to evaluate the cytotoxicity of the association of ZOL (5-500 µM) and of ZOL/biphasic calcium phosphates (BCP). Metabolic activity, cell viability, types of cell death, the cell cycle through, and the migration ability of human gingival fibroblasts were evaluated. (3) Results: ZOL was adsorbed by biphasic calcium phosphate compounds in an aqueous solution. The HGF were sensitive to ZOL toxicity; nevertheless, ZOL/BCP showed a significant protective effect regarding metabolic activity, cell viability, and cell migration. (4) Conclusions: BCP interaction with ZOL reduces or abolishes its toxicity in HGF. This finding represents a potential solution for BRONJ in the case of patients undergoing therapy with ZOL.

Oculo-Facio-Cardio-Dental Syndrome: A Case Report about a Rare Pathological Condition.

(1) Background: Oculo-facio-cardio-dental (OFCD) syndrome is a rare pathological condition with an X-linked dominant trait that only occurs in females; no males are born with OFCD syndrome. This syndrome is characterized by congenital cataracts with secondary glaucoma ocular defects, ventricular and atrial septal defects, or mitral valve prolapses. Facial traits are a long narrow face and a high nasal bridge with a bifid nasal tip. Dental anomalies include radiculomegaly, oligodontia, root dilacerations, malocclusion, and delayed eruption. (2) Methods: This clinical report describes a 26-year-old girl who suffers from OFCD syndrome and who was treated with a multidisciplinary approach. The treatment plan included orthodontic treatment, orthognathic surgery, namely LeFort I and a Bilateral Sagittal Split Osteotomy, and occlusal rehabilitation with implants. (3) Discussion: Early diagnosis and multidisciplinary treatment of orthodontic, orthognathic surgery and occlusal rehabilitation with implants make it possible to maintain tooth function and improve aesthetics with good prognoses for success. In this paper, we report a case of a female patient with OFCD syndrome, who was referred for orthodontic treatment and occlusal rehabilitation and treated with a multidisciplinary approach.

Direct Pulp Capping: What is the Most Effective Therapy?-Systematic Review and Meta-Analysis.

INTRODUCTION: Direct pulp capping therapies use biomaterials to protect exposed tissues, inducing repair through the production of a mineralized barrier. The purpose of this study was to compare the effectiveness of biomaterials and techniques by means of a systematic review and meta-analysis. METHODS: The PubMed, Cochrane, and Embase databases were used to search the literature published from January 1, 1980 until August 31, 2017. Studies that met inclusion criteria were screened by 2 authors individually. The meta-analysis was performed on mineral trioxide aggregate (MTA) cement vs calcium hydroxide cement, tricalcium silicate cement vs MTA cement, and adhesive systems vs CaOH cement and evaluated the success rate, inflammatory response, and dentin bridge formation. RESULTS: Forty-six studies were included in the systematic review, while 22 studies were included in the meta-analysis. There was no significant heterogeneity between the studies. MTA cements showed a significantly higher success rate, in all parameters, compared with calcium hydroxide cements (odds ratio = 2.72; 95% confidence interval [CI] = 1.90-3.90; P = 0.000). However, when compared with the tricalcium silicate cements, there were no statistically significant differences (odds ratio = 1.18; 95% CI = 0.53-2.65; P = 0.672). Adhesive systems showed a significantly lower success rate, in all parameters, compared with calcium hydroxide cements (odds ratio = 0.062; 95% CI = 0.024-0.157; P = 0.000). CONCLUSIONS: MTA cements have a higher success rate, with a lower inflammatory response and a more predictable hard dentin barrier formation than calcium hydroxide cements. However, there were no differences, in these parameters, when MTA cement was compared with tricalcium silicate cements. Dental adhesives systems showed the lowest success rates.

Anaesthesia in Dental Medicine with Local Infiltrative Anaesthetic Technique Versus Diploe Anaesthesia Delivery Systems: Efficacy and Behaviour, an Experimental Study.

INTRODUCTION: This study aimed to compare the analgesic efficacy and the influence of local infiltrative anesthesia techniques, with diploe anesthesia, on the cardiac rhythmMaterial and Methods: We selected 32 healthy volunteers who were given both anaesthetic techniques on tooth 1.4 (0.45 mL of lidocaine with adrenaline, 1:80 000). In the first phase, the volunteers underwent periapical infiltrative anaesthesia. In the second phase, diploe anaesthesia was performed with a QuickSleeper® device. The parameters analysed were pulp response to the electrical test and heart rate of the participants. These parameters were evaluated on five different occasions: before anaesthesia (t0), immediately after anaesthesia (t1), 15 minutes later (t15), 30 minutes later (t30) and 60 minutes later (t60). Statistical analysis of the data was performed using SPSS 2.0 software, with α = 0.05. RESULTS: With the diploe anaesthesia, a level of analgesia was obtained faster. There was a slight increase in heart rate soon after administration of diploe anaesthesia, which stabilized after t15 of the procedure. This technique still proved to be painless. CONCLUSION: Diploe anaesthesia demonstrated better results in terms of analgesia than the infiltrative anaesthesia. It has been reported to be easy, safe and an effective procedure that allows anaesthesia in almost all clinical situations. This approach may offer particular advantages for endodontic therapy, providing greater comfort for the patient.

Introdução: Este estudo teve como objetivo comparar a eficácia analgésica e a influência no ritmo cardíaco das técnicas de anestesia infiltrativa local, com a anestesia diploica. Material e Métodos: Foram selecionados 32 voluntários, saudáveis, aos quais foram administradas ambas as técnicas anestésicas no dente 1.4. (0,45 mL de lidocaína com adrenalina, 1:80 000). Numa primeira fase os voluntários foram sujeitos a anestesia infiltrativa periapical e numa segunda fase foi realizada anestesia diploica, com um dispositivo QuickSleeper®. Os parâmetros analisados foram a resposta pulpar ao teste elétrico e o ritmo cardíaco dos participantes. Estes parâmetros foram avaliados nos tempos: antes da anestesia (t0), logo após a anestesia (t1), 15 minutos depois (t15), 30 minutos depois t(30) e 60 minutos depois (t60). Foi feita análise estatística dos dados obtidos, através do software SPSS 2.0, com α = 0,05. Resultados: Com a anestesia diploica o estado de analgesia foi atingido de forma mais rápida. Registou-se um ligeiro aumento do ritmo cardíaco logo após a administração da anestesia diplóica, que estabilizou após t15 do procedimento. Esta técnica revelou ainda ser indolor. Conclusão: A anestesia diploica demonstrou melhores resultados em termos de analgesia do que o método convencional. Revelou ser um procedimento fácil, seguro e eficaz, que permite anestesiar quase todas as situações clínicas. Esta abordagem apresenta vantagens particularmente para a terapêutica endodôntica, proporcionando maior conforto para o doente.

Bisphosphonate-related osteonecrosis of the jaw: specificities.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe complication that has recently emerged in patients treated with intravenous bisphosphonates for malignant diseases. This complication usually presents after a minor local trauma during a dental treatment. Several etiopathogenic mechanisms of this pathological condition have been proposed, but no model can explain all morphological changes observed at the macroscopic and microscopic level. BRONJ is likely to be related to direct toxicity in the bone and soft tissue cells, due to nitrogen-containing bisphosphonates. This review elucidates the clinical indications and mechanism of action of bisphosphonates, reports some clinical diagnostic criteria for BRONJ, describe the histopathological criteria for BRONJ diagnosis, the potential triggering pathways and the available treatment strategies.