Pathophysiological association between periodontal disease and Alzheimer's disease: Importance of periodontal health in the elderly

BackgroundAs the global aging population is rapidly advancing, recognizing the full potential of periodontal disease (PD) in the onset or progression of Alzheimer's disease (AD) is important for reducing geriatric morbidity. This review explores the possible role of PD in the pathogenesis of AD, as the pathological mechanisms underlying AD are the most well-studied among all types of dementia. The investigation was conducted using the electronic academic databases PubMed and ScienceDirect, employing a combination of keywords “periodontal disease,” “periodontitis,” “Alzheimer's disease,” “dementia,” and “Porphyromonas gingivalis.” After applying the selection and eligibility criteria and removing overlaps, from an initial search finding of 5933 studies, 11 were finally included for qualitative analysis.HighlightThe inflammatory reaction induced by oral pathogenic bacteria related to PD, through complex pathways, may exacerbate inflammation in the central nervous system, thereby contributing to the progression of AD.ConclusionMaintenance of adequate oral hygiene in patients diagnosed with AD is significant because they suffer from a gradual loss of manual dexterity as the disease advances. Additionally, the evidence presents the potential of systemic inflammation from PD-induced pathogenic bacteria, illustrating the grave cyclical progression of AD.     

Variations in root canal morphology of permanent incisors and canines among Asian population: A systematic review and meta-analysis

ObjectivesThis systematic review was designed to measure the pooled prevalence of morphological variations in the root canal of permanent incisors and canines among Asian adults.MethodsAn electronic search was conducted in the PubMed, Scopus, and EBSCO databases, and relevant studies were included. Studies reporting on the Vertucci canal configuration (types I to VIII) were included. A weighted proportion (pooled prevalence) with 95% confidence interval was calculated for each canal type, and the outcome was stratified based on country, technique of assessment, gender, and age.ResultsSixty articles were included in the final review. In all types of maxillary anterior teeth, the pooled prevalence of type I canal configuration was greater than 97%, whereas mandibular central incisor, lateral incisor, and canines had a prevalence of 78.4%, 69.2%, and 91.1%, respectively. Studies considering mandibular anterior teeth as a single entity had a lower prevalence of type I configuration (70.1%). Variations in root canal configurations were also observed between countries. Among gender, males had a significantly lower prevalence of type I and a higher prevalence of type II and III canal configurations in the mandibular anterior teeth. A variation in canal types was also noted with advancing age, with younger age groups showing more variations.ConclusionThe majority of maxillary and mandibular anterior teeth have type I Vertucci canal configuration, but variations in mandibular anterior teeth, especially lateral incisors, are also common. Variations were also observed among population, gender, age, and prevalence based on the diagnostic techniques used.     

The influence of periodontal status and serum biomarkers on salivary leptin levels in systemic lupus erythematosus patients

ObjectiveThis study aimed to investigate the influence of periodontal status, clinical data, and serum markers on salivary leptin levels in patients with systemic lupus erythematosus (SLE).MethodsA case–control study was conducted with 38 patients with SLE and 29 healthy controls. Periodontal data included periodontal probing depth (PPD), clinical attachment level (CAL), and gingival bleeding on probing (BOP). Stimulated saliva samples were collected to analyze salivary leptin levels. Clinical and serum data were collected from the SLE group. Statistical analysis included the t-test, Mann–Whitney test, Spearman correlation coefficient, and a structural equation model.ResultsThe SLE group had a lower salivary leptin level than the control group (P = 0.002). The model revealed that SLE had an inverse and independent effect on salivary leptin (standardized estimate =  ? 0.289, P = 0.023). Moreover, salivary leptin level negatively correlated with the serum levels of triglyceride, creatinine, and leukocytes, positively correlated with the serum total cholesterol, but was not significantly correlated with the periodontal status.ConclusionThese findings suggest that patients with SLE have a lower salivary leptin level. In addition, the level of salivary leptin does not appear to be related to periodontal status in patients with SLE.     

Remaining dentinal thickness after simulated post space preparation and the fit of prefabricated posts to root canal preparation shapes

BackgroundPost space preparation can increase the risk of experiencing perforation and root fracture. The authors assessed remaining dentin thickness after post space preparation and the fit of different prefabricated posts to root canal preparation systems in a theoretical model.MethodsTen datasets per type of tooth from cone-beam computed tomography were analyzed to determine the minimum root diameter from 5 through 13 mm from the apical foramen. The preparation shapes of 10 root canal preparation systems were calculated and compared with the root dimensions to determine the remaining dentin thickness. Eight post brands were compared with root dimensions to determine the areas where there was less than 1 mm dentin thickness.ResultsThe average root canal preparation shape produced canal diameters of 0.57 mm at 5 mm from the canal terminus and 0.94 mm at 13 mm from the canal terminus. The mean post size tip diameter was 1.03 mm, which is larger than the dimensions of the average canal preparation. Post preparation would result in less than 1 mm of dentin thickness remaining in premolars, smaller roots of molars, and mandibular incisors. The area with less than 1 mm of dentin thickness was around the post tip.ConclusionsEndosequence Fiber Post (Brasseler USA), RelyX Fiber Post 3D (3M), and Rebilda (VOCO) were the better fitting posts with the root canal preparation shapes.Practical ImplicationsMany posts would result in less than 1 mm dentin thickness. Clinicians should use posts that fit their root canal preparations to minimize dentin removal.     

Association between periodontal care and hospitalization with acute myocardial infarction

BackgroundEach year there are 800,000 myocardial infarctions in the United States. There is an increased risk of hospitalization for acute myocardial infarction (AMI) for those with periodontal disease. Yet, there is a paucity of knowledge about downstream care of AMI and how this varies with periodontal care status. The authors' aim was to examine the association between periodontal care and AMI hospitalization and 30 days after acute care.MethodsUsing the MarketScan database, the authors conducted a retrospective cohort study among patients with both dental insurance and medical insurance in 2016 through 2018 who were hospitalized for AMI in 2017.ResultsThere were 2,370 patients who had dental and medical coverage for 2016 through 2018 and received oral health care in 2016 through 2017 and had an AMI hospitalization in 2017. Forty-seven percent received regular or other oral health care, 7% received active periodontal care, and 10% received controlled periodontal care. More than one-third of patients (36%) did not have oral health care before the AMI hospitalization. After adjusting for patient characteristics, we found that patients in the controlled periodontal care group were significantly more likely to have visits during the 30 days after AMI hospitalization (adjusted odds ratio, 1.63; 95% CI, 1.07 to 2.47; P = .02).ConclusionsWe found that periodontal care was associated with more after AMI visits. This suggests that there is a benefit to incorporating oral health care and medical care to improve AMI outcomes.Practical ImplicationsNeeding periodontal care is associated with more favorable outcomes related to AMI hospitalization. Early intervention to ensure stable periodontal health in patients with risk factors for AMI could reduce downstream hospital resource use.     

Importance of anatomy in dental implant surgery

BackgroundThe knowledge of nerves and vessels in the maxillofacial region, particularly the anatomical structures in the maxilla, mandible, tongue muscles, and salivary glands, is essential for dental surgeons. In addition, the structures in the mandibular canal, palate, and maxillary sinus should be understood well.HighlightThe arteries and nerves in the maxillofacial region were observed in this study. Some variations in the origin of the inferior alveolar artery were found. Notably, the variations in the origin of the inferior alveolar artery from that of the external carotid artery and a double origin of the inferior alveolar artery were observed. Thus, the maxillary artery may originate from the external carotid and stapedial arteries. The following points are important. (1)The greater palatine artery is always located deeper than the greater palatine nerve. (2)The posterior superior alveolar artery often runs through the compact bone of the maxilla. Using CT scans, the canal of the artery can be observed. (3)Variations in origins of the inferior alveolar artery have been observed. The origin of the inferior alveolar nerve may differ depending on the course of the maxillary artery.ConclusionsDental practitioners should, therefore, have a comprehensive knowledge of the anatomy of the maxillofacial region and its variations. Without this knowledge, they should not operate on patients.     

Vitamin C and eggshell membrane facilitate orthodontic tooth movement and induce histological changes in the periodontal tissue

ObjectivesCollagen remodeling of the periodontal tissue is an important mechanism that involves several biologically active substances to accelerate orthodontic tooth movement. It is known that Vitamin C (VC) enhances collagen production and induces tooth movement. Moreover, the eggshell membrane (ESM) is an integral component of various formulations used to promote wound healing. The purpose of our study was to determine the effects of combined treatment with VC and ESM on periodontal tissues during tooth movement.MethodsNine-week-old male osteogenic disorder Shionogi rats were randomized into four groups: control, VC, ESM, and VC + ESM. The control group was given tap water, and the VC, ESM, and VC + ESM groups were orally administered 0.1% VC solution, 1 wt% ESM solution, and a combination of 0.1 wt% VC and 1 wt% ESM solutions, respectively. A force of 25 or 75 g was applied for 10 days to produce orthodontic tooth movement. Distances of tooth movement were measured on days 3, 7, and 10 of treatment. Histological examination of the periodontal ligament was performed to determine the increase in type I and III collagen levels in response to treatment.ResultsDistances of tooth movement were significantly greater in the VC + ESM group than in the control group. The compression area of the alveolar bone showed increased osteoclastic activity and higher levels of bone resorption in the VC + ESM group. Expression levels of type I and III collagen in the tension area of the alveolar bone were higher in the VC + ESM group than in the control group.ConclusionsThis study revealed that the combined administration of VC and ESM accelerated tooth movement by protecting the periodontal tissue during orthodontic treatment. The combined clinical application of VC and ESM could potentially shorten orthodontic treatment time.     

Sclerostin and its role as a bone modifying agent in periodontal disease

BackgroundPeriodontitis is a highly prevalent inflammatory disease affecting the periodontium that results from an imbalance between periodontopathogens and host mechanisms. Continuous progression of the disease may lead to tissue and bone destruction, eventually resulting in tooth loss. The extent of bone loss depends on the dysregulated host immune response. Various host-elicited molecules play a major role in disease progression. The discovery of the glycoprotein sclerostin and its role as a regulator of bone mass has led to a better understanding of bone metabolism.HighlightSclerostin, which is primarily expressed by osteocytes, is a negative regulator of bone formation. It is a potent antagonist of the canonical Wingless-related integration site (Wnt) pathway, which is actively involved in bone homeostasis. Sclerostin is known to stimulate bone resorption by altering the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa- β ligand (RANKL) balance. Additionally, in periodontitis, activation of the inflammatory cascade also increases the synthesis of sclerostin.ConclusionThe recently discovered sclerostin antibody has emerged as a positive therapeutic tool for the treatment of metabolic bone diseases. It has been reported to improve bone strength, bone formation, osseointegration around implants and lower the risk of bone fractures in various animal and human models. This review describes the properties and action of sclerostin, its role in periodontal diseases, and the advent and efficacy of sclerostin antibodies.     

Tetracycline impregnated bone grafts in the management of peri-implantitis and guided bone regeneration around dental implants: A systematic review

BackgroundRehabilitation of dental arches with the help of dental implants has been revolutionary and a significant part of research is devoted to increasing its success rate. One of the most common causes of failure of dental implants is peri-implantitis caused due to microbial invasion. Newer strategies are being adapted for the treatment of peri-implantits and recent surgical management with the help of antibiotic-impregnated bone grafts shows a promising future.Aim and objectivesThis study aimed to test the efficacy of bone grafts incorporating tetracycline and its derivatives in the treatment of peri-implantits and guided bone regeneration with the estimation of clinical and radiographic parameters.MethodsA thorough search was made on eminent databases such as PubMed, Embase, Scopus, and Cochrane Library database for published literature on tetracycline impregnated bone grafts used either in the management of peri-implantitis or for guided bone regeneration around dental implants.The measures of outcome were clinical attachment loss or probing depth around dental implants and radiographic bone height.ResultsNine potentially eligible full-text published articles including case reports, case series, observational studies, and randomized controlled trials were selected for review. Most of the studies reviewed; reported a reduction in probing depth and an increase in bone height and density after placement of tetracycline bone grafts around the dental implant.ConclusionThe incorporation of tetracycline into the bone grafts shows promising results as an agent of local delivery around dental implants in the management of peri-implantitis and for guided bone regeneration. Future trials are required to produce a body of evidence and to facilitate the translation of this procedure into clinical practice.     

Periodontal tissue regeneration by recombinant human collagen peptide granules applied with β-tricalcium phosphate fine particles

ObjectivesRecombinant human collagen peptide (RCP) is a recombinantly created xeno-free biomaterial enriched in arginine-glycine-aspartic acid sequences with good processability whose use for regenerative medicine applications is under investigation. The biocompatibility and osteogenic ability of RCP granules combined with β-tricalcium phosphate (TCP) submicron particles (β-TCP/RCP) were recently demonstrated. In the present study, β-TCP/RCP was implanted into experimental periodontal tissue defects created in beagles to investigate its regenerative effects.MethodsAn RCP solution was lyophilized, granulated, and thermally cross-linked into particles approximately 1 mm in diameter. β-TCP dispersion (1 wt%; 500 μL) was added to 100 mg of RCP granules to form β-TCP/RCP. A three-walled intrabony defect (5 mm × 3 mm × 4 mm) was created on the mesial side of the mandibular first molar and filled with β-TCP/RCP.ResultsA micro-computed tomography image analysis performed at 8 weeks postoperative showed a significantly greater amount of new bone after β-TCP/RCP grafting (2.2-fold, P < 0.05) than after no grafting. Histological findings showed that the transplanted β-TCP/RCP induced active bone-like tissue formation including tartaric acid-resistant acid phosphatase– and OCN-positive cells as well as bioabsorbability. Ankylosis did not occur, and periostin-positive periodontal ligament-like tissue formation was observed. Histological measurements performed at 8 weeks postoperative revealed that β-TCP/RCP implantation formed 1.7-fold more bone-like tissue and 2.1-fold more periodontal ligament-like tissue than the control condition and significantly suppressed gingival recession and epithelial downgrowth (P < 0.05).Conclusionsβ-TCP/RCP implantation promoted bone-like and periodontal ligament–like tissue formation, suggesting its efficacy as a periodontal tissue regenerative material.     

Efficacy of artificial intelligence in the detection of periodontal bone loss and classification of periodontal diseases: A systematic review

BackgroundArtificial intelligence (AI) can aid in the diagnosis and treatment planning of periodontal disease by means of reducing subjectivity. This systematic review aimed to evaluate the efficacy of AI models in detecting radiographic periodontal bone loss (PBL) and accuracy in classifying lesions.Types of Studies ReviewedThe authors conducted an electronic search of PubMed, Scopus, and Web of Science for articles published through August 2022. Articles evaluating the efficacy of AI in determining PBL were included. The authors assessed the articles using the Quality Assessment for Studies of Diagnostic Accuracy tool. They used the Grading of Recommendations Assessment, Development and Evaluation criteria to evaluate the certainty of evidence.ResultsOf the 13 articles identified through electronic search, 6 studies met the inclusion criteria, using a variety of AI algorithms and different modalities, including panoramic and intraoral radiographs. Sensitivity, specificity, accuracy, and pixel accuracy were the outcomes measured. Although some studies found no substantial difference between AI and dental clinicians’ performance, others showed AI’s superiority in detecting PBL. Evidence suggests that AI has the potential to aid in the detection of PBL and classification of periodontal diseases. However, further research is needed to standardize AI algorithms and validate their clinical usefulness.Practical ImplicationsAlthough the use of AI may offer some benefits in the detection and classification of periodontal diseases, the low level of evidence and the inconsistent performance of AI algorithms suggest that caution should be exercised when considering the use of AI models in diagnosing PBL. This review was registered at PROSPERO (CRD42022364600).     

Adipose-derived mesenchymal stem cells promote salivary duct regeneration via a paracrine effect

ObjectivesThe self-regeneration of exocrine tissues, including salivary glands, is limited and their regeneration mechanism has not yet been fully elucidated. Here we identify the role of adipose-derived mesenchymal stem cells (AMSCs) in salivary gland regeneration.MethodsAMSCs expressing mesenchymal stem cell markers were applied to a submandibular gland injury model and the mechanism of salivary gland repair and regeneration was analyzed.ResultsTransplanted green fluorescent protein (GFP)-labeled AMSCs grew tightly together and promoted ductal regeneration in the regenerative nodule, with slight infiltration of nonspecific immune cells. A comprehensive gene analysis through RNA-sequencing revealed increased expression of bone morphogenetic protein (BMP), transforming growth factor (TGF), and Wnt in AMSC-transplanted regenerative nodules. The factors released from AMSCs scavenge hydrogen peroxidase-induced reactive oxygen species (ROS) through Wnt promoter activity in vitro. Furthermore, AMSC-conditioned medium recovered the growth of the hydrogen peroxidase-damaged primordium of the submandibular gland culture ex vivo.ConclusionsThese results suggest that AMSC-released factors scavenge ROS and maintain salivary gland repair and regeneration via paracrine effects. Thus, AMSCs could be a practical and applicable tool for use in salivary gland regeneration.     

Amixicile depletes the ex vivo periodontal microbiome of anaerobic bacteria

ObjectivesAlthough periodontal diseases result from overgrowth of anaerobic bacteria, the effect of a specific knockdown of anaerobes on the disease outcome has yet to be examined. We have reported that amixicile, a non-toxic, readily bioavailable, and novel antimicrobial, specifically targets selected oral anaerobes through inhibition of the activity of pyruvate ferredoxin oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate.MethodsHere, we generated an ex vivo microbiome derived from gingival pockets of human subjects with chronic periodontal disease and evaluated the efficacy of amixicile in generating a specific knockdown of anaerobic bacteria present in the microbiome.ResultsOur bioinformatics analysis identified PFOR-like coding capacity in over 100 genomes available from the HOMD database. Many of those bacteria were present in our ex vivo microbiome. Significantly, the anaerobic pathogens relying on PFOR for energy generation were specifically reduced in abundance following treatment with amixicile while non-PFOR bacteria were spared. Specifically, Prevotella, Veillonella, Slackia, Porphyromonas, Treponema, Megasphera, and Atobium were reduced in abundance. Such treatment resulted in the conversion of a microbiome resembling a microbiome derived from sites with periodontal disease to one resembling a microbiome present at healthy sites. We also compared the inhibitory spectrum of amixicile to that of metronidazole and showed that the antibiotics have a similar inhibitory spectrum.ConclusionsThis work further demonstrates that amixicile has the potential to reverse and prevent the outgrowth of anaerobic pathogens observed in subjects with periodontal disease.     

Application of hiPSCs in tooth regeneration via cellular modulation

BackgroundInduced pluripotent stem cell (iPSC)-based technology provides limitless resources for customized development of organs without any ethical concerns. In theory, iPSCs generated from terminally differentiated cells can be induced to further differentiate into all types of organs that are derived from the embryonic germ layers. Since iPSC reprogramming technology is relatively new, extensive efforts by the researchers have been put together to optimize the protocols to establish in vitro differentiation of human iPSCs (hiPSCs) into various desirable cell types/organs.HighlightsIn the present study, we review the potential application of iPSCs as an efficient alternative to primary cells for modulating signal molecules. Furthermore, an efficient culture system that promotes the differentiation of cell lineages and tissue formation has been reviewed. We also summarize the recent studies wherein tissue engineering of the three germ layers has been explored. Particularly, we focus on the current research strategies for iPSC-based tooth regeneration via molecular modulation.ConclusionIn recent decades, robust knowledge regarding the hiPSC-based regenerative therapy has been accumulated, especially focusing on cellular modulation. This review provides the optimization of the procedures designed to regenerate specific organs.     

Insight into the molecular pathogenesis of odontogenic lesions

BackgroundOdontogenic tumors, derived from epithelial, ectomesenchymal, and/or mesenchymal elements of the tooth-forming apparatus, constitute a heterogeneous group of lesions, including hamartomas, benign and malignant neoplasms with metastatic capabilities.HighlightThis review provides a comprehensive overviewof the pathogenesis of odontogenic tumors and explains the associated molecular events in the context of hallmarks of cancer established by Hanahan D and Weinberg RA. Diagrammatic representations depicted in the article would facilitate easier understanding.ConclusionA better understanding of the pathogenesis of the lesions may assist in determining patient's prognosis and devising better targeted therapeutic treatment, thus, reducing the morbidity and mortalityof patients.     

Three-dimensional cellular visualization in mouse apical periodontitis using combined whole-mount staining and optical tissue clearing

Apical periodontitis is an inflammatory disease involving lesions located within the jawbone. Histological evaluations generally require decalcification and sectioning, which has limited our understanding of the three-dimensional (3D) organization and spatial distribution of different immune cell types in these lesions. A recently developed technique combining tissue clearing and whole-mount immunofluorescent labeling allows us to acquire such information from the deep tissue without sectioning. However, whole-mount immunofluorescent labeling in the jawbone requires further development. Here we provide a straightforward and efficient protocol to achieve 3D immunofluorescent imaging of murine periapical lesions.     

A comparative analysis of public and private dental benefit payer types for the provision and outcomes of root canal therapy on permanent teeth of children and adolescents in Massachusetts

BackgroundDespite substantial increases in dental benefits and improvements in the use of dental services among children and adolescents in the United States, oral health disparities according to dental insurance payer type persist.MethodsThe authors used an all-payer claims (2013-2017) database to perform a comparative analysis of the provision and treatment outcomes of an endodontic procedure (root canal therapy) in the permanent teeth of a pediatric population aged 6 through 18 years, according to dental insurance payer type. Statistical analyses, including logistic regression, Cox proportional hazards regression, and the Kaplan-Meier method, were performed at person and tooth levels.ResultsCompared with privately insured children and adolescents, public-payer children and adolescent beneficiaries were more likely to have had root canal therapy (adjusted odds ratio, 1.91; 95% CI, 1.73 to 2.11) and had poorer treatment outcomes associated with the procedure (adjusted hazard ratio, 2.19; 95% CI, 1.53 to 3.14; P < .0001) during the study period. Those enrolled in private insurance were more likely to receive treatment from an endodontist (specialist in providing root canal therapy) (P < .0001). Amounts allowed and paid by the insurer were significantly higher for private payers (P < .001).ConclusionsThere were significant differences in the provision and outcomes of endodontic treatment between privately and publicly insured children and adolescents.Practical ImplicationsDespite ostensibly equal access to care, differences in the provision of oral health care exist between privately and publicly insured patients. These differences may be contributing to persisting oral health disparities.     

Efficacy of adjuvant ozone therapy in reducing postsurgical complications following impacted mandibular third-molar surgery: A systematic review and meta-analysis

BackgroundResults from several randomized controlled trials have shown a beneficial effect of ozone in reducing postsurgical complications after impacted mandibular third-molar surgery, but the literature is lacking a systematic review and meta-analysis.MethodsThe authors conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines after exclusion and inclusion criteria were applied and the following outcome parameters were evaluated: pain, swelling, trismus, quality of life, number of analgesics consumed, and adverse events. RevMan Cochrane Collaboration software, Version 5.3, was used to perform meta-analysis and the Grading of Recommendation Assessment, Development and Evaluation approach was used to rate the certainty of evidence.ResultsPatients who underwent adjuvant ozone application reported lower pain scores than patients in the control group at 24 hours after surgery (95% CI, –3.94 to –1.56) and at 7 days (95% CI, –1.67 to –0.78). Pooled analysis of all 4 included trials revealed a standardized mean difference (SMD) in swelling of –0.44 at 24 hours, 0.63 at 72 hours, and –0.87 at 7 days after surgery in the experimental group. Higher mean estimates in mouth opening were experienced by patients who received ozone at 24 hours (SMD, 2.74; 95% CI, –1.93 to 7.41; 4 studies, 133 patients), 72 hours (SMD, 2.77; 95% CI, –0.63 to 6.17; 4 studies, 133 patients), and 7 days after surgery (SMD, 1.42 SMD; 95% CI, –1.34 to 4.18; 4 studies, 133 patients).Practical ImplicationsEvidence suggests that adjuvant ozone application can offer some benefit for reducing pain, improving quality of life, and decreasing mean intake of analgesics after impacted mandibular third-molar surgery, but it is not effective in reducing facial swelling and trismus, which paves the way for future research.