The Expression Patterns of Non-Coding RNAs in Periodontal Disease.

During the last few decades there has been a growing interest in understanding the involvement of epigenetics in the pathogenesis and treatment of periodontal disease. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), may serve as epigenetic modifiers affecting the expression of genes involved in the pathogenesis of inflammatory and autoimmune diseases. There is increasing evidence supporting the idea that the function of all three types of ncRNAs seems to be interdependent. LncRNAs can act as miRNA decoys, while circRNAs can act as miRNA sponges, leading to the re-expression of miRNA target genes. The purpose of this review is to evaluate the expression patterns of ncRNAs in periodontal disease. Studies demonstrate a positive correlation between miRNA expression and periodontitis; however, this cannot be claimed for lncRNAs and circRNAs, which appear to be differentially expressed in periodontitis patients. Several studies have also suggested utilizing ncRNAs as diagnostic and prognostic biomarkers in periodontitis, or even as potential therapeutic targets; Nevetheless, the evidence to support this is premature. Future well-designed research remains necessary to establish the functional role of ncRNAs in the evolution and progression of periodontal disease.

Oral manifestations of nine individuals with Williams syndrome. A case series.

AIMS: Williams syndrome (WS) is a congenital developmental disorder characterized, mainly, by distinctive facial features, cardiovascular anomalies, growth delay and a typical neurobehavioral profile. The oral manifestations have not been sufficiently described and, therefore, the aim of the current study was to present the clinical, radiographic and microbiological findings of individuals with WS. METHODS AND RESULTS: A series of nine WS individuals (seven females) with mean age 21 years-old were evaluated. A complete intraoral clinical examination, a radiographic analysis using panoramic and cephalometric x-ray and a supra- and sub-gingival microbiological profiling were performed. We observed abnormal tooth morphology, excessive interdental spacing, congenitally missing permanent teeth and malocclusion. High levels of DMFT were observed and gingivitis was present in all subjects. Bacteria related to periodontal disease were detected in dental plaque. Three patients were classified with a gingival phenotype type I according to the Maynard and Wilson classification. The sella turcica bridging was a novel finding for this group of patients. CONCLUSION: Due to the elevated prevalence of gingivitis, caries and malocclusion, a multidisciplinary approach including dental follow-ups should be the standard of care in WS patients.

Periodontal diseases and adverse pregnancy outcomes. Present and future.

For more than two decades the possible association between periodontal diseases and adverse pregnancy outcomes has been extensively evaluated. Numerous observational, intervention, and mechanistic studies have offered valuable information on this topic. However, several methodologic limitations still remain a significant drawback for this set of investigations, and therefore safe conclusions are not always easy to draw. Unfortunately, despite the strong recommendations from the scientific community, recent studies have not sufficiently addressed these limitations and, therefore, have not significantly altered our perception regarding the association between periodontal disease and adverse pregnancy outcomes. This review briefly describes the established knowledge and gives emphasis to the current literature. In addition, owing to the main theme of this Periodontology 2000 volume, special reference will be made regarding the results from European studies on periodontal disease and adverse pregnancy outcomes. Finally, new strategies and research guidelines are proposed in order to move on to the next level of evidence that will help connect the theoretical knowledge with meaningful clinical interventions that will benefit our pregnant patients and their offspring.

Clinical evaluation of different alveolar ridge preservation techniques after tooth extraction: a randomized clinical trial.

OBJECTIVE: The aim of the present randomized controlled trial (RCT) was to evaluate the efficacy of different alveolar ridge preservation (ARP) techniques on dimensional alterations after tooth extraction, based on clinical measurements. BACKGROUND: Alveolar ridge preservation (ARP) is a common procedure in every day clinical practice, when dental implants are involved in treatment planning. In ARP procedures, a bone grafting material is combined with a socket sealing (SS) material in order to compensate the alveolar ridge dimensional alterations after tooth extraction. Xenograft and allograft are the most frequently used bone grafts in ARP, while free gingival graft (FGG), collagen membrane, and collagen sponge (CS) usually applied as SS materials. The evidence comparing xenograft and allograft directly in ARP procedure is scarce. In addition, FGG is usually combined with xenograft as SS material, while the evidence combing allograft with FGG is absent. Moreover, CS could probably be an alternative choice in ARP as SS material, since it has been used in previous studies but more clinical trials are required to evaluate its effectiveness. MATERIALS AND METHODS: Forty-one patients were randomly assigned in four treatment groups: (A) freeze-dried bone allograft (FDBA) covered with collagen sponge (CS), (B) FDBA covered with free gingival graft (FGG), (C) demineralized bovine bone mineral xenograft (DBBM) covered with FGG, and (D) FGG alone. Clinical measurements were performed immediately after tooth extraction and 4 months later. The related outcomes pertained to both vertical and horizontal assessment of bone loss. RESULTS: Overall, groups A, B, and C presented significantly less vertical and horizontal bone resorption compared to group D. No statistically significant difference was observed between allograft and xenograft, except for the vertical bone resorption at the buccal central site, where xenograft showed marginally statistically significantly reduced bone loss compared to allograft (group C vs group B: adjusted ß coef: 1.07 mm; 95%CI: 0.01, 2.10; p = 0.05). No significant differences were observed in hard tissue dimensions when CS and FGG were applied over FDBA. CONCLUSIONS: No differences between FDBA and DBBM could practically be confirmed. In addition, CS and FGG were equally effective socket sealing materials when combined with FDBA, regarding bone resorption. More RCTs are needed to compare the histological differences between FDBA and DBBM and the effect of CS and FGG on soft tissue dimensional changes. CLINICAL RELEVANCE: Xenograft and allograft were equally efficient in ARP 4 months after tooth extraction in horizontal level. Xenograft maintained the mid-buccal site of the socket marginally better than the allograft, in vertical level. FGG and CS were equally efficient as SS materials regarding the hard tissue dimensional alterations. TRIAL REGISTRATION: Clinical trial registration Number: NCT04934813 (clinicaltrials.gov).

Oral manifestations of eleven individuals with Noonan syndrome. A case series.

AIMS: Noonan syndrome (NS) is a clinically and genetically heterogeneous condition characterized by distinctive facial features, short stature, and congenital heart defects. The oral manifestations have not been sufficiently described. In an attempt to enrich our understanding regarding the oral manifestations, the aim of the current study was to present the clinical, radiographic, and microbiological findings of eleven subjects with NS syndrome. METHODS AND RESULTS: A complete intraoral clinical evaluation, a radiographic analysis using panoramic and cephalometric x-rays, and a supra- and sub-gingival microbiological profiling of 20 periodontal and cariogenic microbiota using the checkerboard DNA-DNA hybridization technique were performed in a series of 11 NS individuals. Compared to previous reports very few dental findings were present. Gingivitis and carious lesions were present in all subjects and could be related to poor oral hygiene. High-arched palate and malocclusions such as crossbite, open-bite, and deep-bite were very common findings but without a specific pattern. Two findings that have not been reported before included the different shapes of the condyles and the irregular shape of the sella turcica. CONCLUSION: Due to the elevated prevalence of gingivitis, caries, and malocclusion, a multidisciplinary approach including dental follow-ups should be the standard care in NS patients.

Etiology and Treatment of Peri-Implant Soft Tissue Dehiscences: A Narrative Review.

Implant soft tissue dehiscences compromise not only the aesthetics of the supported restorations but implant survival in the long run. The aim of this narrative review was to briefly present the causative factors of buccal peri-implant soft tissue dehiscences (PSTDs), how these are classified, and the current therapeutic approaches. Implant malposition and the thin peri-implant phenotype are the two major determinants for the occurrence of PSTDs, but other risk factors have also been identified. The most common surgical procedure for treating PSTDs is the split-thickness coronally advanced flap combined with either a connective tissue graft or acellular dermal matrix materials. However, depending on the class and subtype of the dehiscence, the combination of surgical techniques with modifications in the restoration may further ameliorate the final result. In general, within a five-year follow-up period, most techniques lead to a satisfactory aesthetic result, although full coverage of the implant/abutment surface is not always achievable, especially in more extended lesions.

Association between periodontal disease and vulnerable plaque morphology in patients undergoing carotid endarterectomy.

BACKGROUND: Periodontal disease (PD) is a chronic inflammatory oral condition with potentially important systemic sequelae. We sought to determine whether the presence of PD in patients with severe carotid disease was associated with morphological features consistent with carotid plaque instability. METHODS: A total of 52 dentate patients hospitalized for carotid endarterectomy (CEA) had standardized assessments of their periodontal status, including measurements of probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BoP). Carotid plaque morphology was assessed by ultrasound using the gray scale median (GSM) score and by immunohistochemistry using anti-CD68 and anti-alpha-actin antibodies, markers for macrophages and smooth muscle cells (SMCs) respectively. RESULTS: In total 30/52 patients (58%) had PD. Significant associations were noted between low GSM on ultrasound and each mm in PPD (p = 0.001), each mm in CAL (p = 0.002) and with a 10% increase in BoP (p = 0.009). Using the standardized PERIO definition the association remained robust (aOR = 10.4 [95% CI:2.3-46.3], p = .002). Significant associations were also observed with high macrophage accumulation and each individual PD measure (p < 0.01 for PPD, CAL and BoP) and with the PERIO definition (aOR = 15 [95% CI:1.8-127.8], p = .01). Similarly, low SMC density was also significantly associated with individual measures of PD (p < 0.05 for PPD, CAL and BoP), but not with the PERIO definition (aOR 3.4 [95% CI:0.9-12.8], p = .07). CONCLUSIONS: The presence of PD was significantly associated with both ultrasound and immunohistochemistry features of carotid plaque instability in patients undergoing CEA.

Periodontal disease and adverse pregnancy outcomes.

Periodontal diseases are considered not only to affect tooth-supporting tissues but also to have a cause-and-effect relationship with various systemic diseases and conditions, such as adverse pregnancy outcomes. Mechanistic studies provide strong evidence that periodontal pathogens can translocate from infected periodontium to the feto-placental unit and initiate a metastatic infection. However, the extent and mechanisms by which metastatic inflammation and injury contribute to adverse pregnancy outcomes still remain unclear. The presence of oral bacteria in the placenta of women with term gestation further complicates our understanding of the biology behind the role of periodontal pathogens in pregnancy outcomes. Epidemiological studies demonstrate many methodological inconsistencies and flaws that render comparisons difficult and conclusions insecure. Therefore, despite the fact that a number of prospective studies show a positive association between periodontal diseases and various adverse pregnancy outcomes, the evidence behind it is still weak. Future well-designed explanatory studies are necessary to verify this relationship and, if present, determine its magnitude. The majority of high-quality randomized controlled trials reveal that nonsurgical periodontal therapy during the second trimester of gestation does not improve pregnancy outcomes. From a biological standpoint, this can be partially explained by the fact that therapy rendered at the fourth to sixth months of pregnancy is too late to prevent placental colonization by periodontal pathogens and consequently incapable of affecting pathogen-induced injury at the feto-placental unit. Thus, interventions during the preconception period may be more meaningful. With the increase in our understanding on the potential association between periodontal disease and adverse pregnancy outcomes, it is clear that dental practitioners should provide periodontal treatment to pregnant women that is safe for both the mother and the unborn child. Although there is not enough evidence that the anti-infective therapy alters pregnancy outcomes, it improves health-promoting behavior and periodontal condition, which in turn advance general health and risk factor control.

Association of Vitamin D With Periodontal Disease: A Narrative Review.

PURPOSE: To present a review of available literature on the association of vitamin D and periodontal disease. MATERIALS AND METHODS: A thorough search of articles was carried out on the databases PUBMED and MEDLINE regarding vitamin D and periodontal disease. The selected literature included cross-sectional, case-control and prospective and retrospective cohort studies. The main aspects of the association evaluated were a) the association of 25(OH)D and 1,25(OH)2D3 with periodontal disease severity, periodontal disease progression and tooth loss, b) the effect of vitamin D supplementation on periodontal health and c) the association of vitamin D receptor polymorphisms with periodontal disease. A brief overview of the biological mechanisms linking periodontal disease with vitamin D was also included. RESULTS AND CONCLUSIONS: There is conflicting evidence regarding the effects of 25(OH)D on periodontal disease severity, progression and tooth loss, with some studies reporting beneficial effects of higher 25(OH)D serum concentrations on periodontal health and tooth retention, whereas others could not find such an association. Limited evidence also supports a positive association between 1,25(OH)2D3 and periodontal health as well as a trend towards better periodontal health with vitamin D supplementation. Finally, various vitamin D polymorphisms were associated with chronic and aggressive periodontitis, with different outcomes reported for the various ethnic populations assessed.

Detection Accuracy of Bone Defects Depending on Exposure Settings of Cone Beam Computed Tomography.

Despite the widespread use of cone beam computed tomography (CBCT), few articles have been published to assess the accuracy in detecting alveolar bone defects using different CBCT exposure settings. A human cadaver with rounded bone defects in various locations was scanned using a CBCT scanner at different settings. Four examiners twice studied 1,500 cross-sectional digital and printed slices for defect presence, location, and size. High-resolution zoom mode achieved the highest overall accuracy. Moreover, apical location of the defects significantly affected overall accuracy. Bone defect detection depends upon exposure settings of CBCT scans. Exposure settings and field of view dimensions should be individualized per case.

Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms.

AIM: To evaluate the evidence on potential biological pathways underlying the possible association between periodontal disease (PD) and adverse pregnancy outcomes (APOs). MATERIAL & METHODS: Human, experimental and in vitro studies were evaluated. RESULTS: Periodontal pathogens/byproducts may reach the placenta and spread to the foetal circulation and amniotic fluid. Their presence in the foeto-placental compartment can stimulate a foetal immune/inflammatory response characterized by the production of IgM antibodies against the pathogens and the secretion of elevated levels of inflammatory mediators, which in turn may cause miscarriage or premature birth. Moreover, infection/inflammation may cause placental structural changes leading to pre-eclampsia and impaired nutrient transport causing low birthweight. Foetal exposure may also result in tissue damage, increasing the risk for perinatal mortality/morbidity. Finally, the elicited systemic inflammatory response may exacerbate local inflammatory responses at the foeto-placental unit and further increase the risk for APOs. CONCLUSIONS: Further investigation is still necessary to fully translate the findings of basic research into clinical studies and practice. Understanding the systemic virulence potential of the individual's oral microbiome and immune response may be a distinctly different issue from categorizing the nature of the challenge using clinical signs of PD. Therefore, a more personalized targeted therapy could be a more predictive answer to the current "one-size-fits-all" interventions.

Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms.

AIM: To evaluate the evidence on potential biological pathways underlying the possible association between periodontal disease (PD) and adverse pregnancy outcomes (APOs). MATERIAL & METHODS: Human, experimental and in vitro studies were evaluated. RESULTS: Periodontal pathogens/byproducts may reach the placenta and spread to the foetal circulation and amniotic fluid. Their presence in the foeto-placental compartment can stimulate a foetal immune/inflammatory response characterized by the production of IgM antibodies against the pathogens and the secretion of elevated levels of inflammatory mediators, which in turn may cause miscarriage or premature birth. Moreover, infection/inflammation may cause placental structural changes leading to pre-eclampsia and impaired nutrient transport causing low birthweight. Foetal exposure may also result in tissue damage, increasing the risk for perinatal mortality/morbidity. Finally, the elicited systemic inflammatory response may exacerbate local inflammatory responses at the foeto-placental unit and further increase the risk for APOs. CONCLUSIONS: Further investigation is still necessary to fully translate the findings of basic research into clinical studies and practice. Understanding the systemic virulence potential of the individual's oral microbiome and immune response may be a distinctly different issue from categorizing the nature of the challenge using clinical signs of PD. Therefore, a more personalized targeted therapy could be a more predictive answer to the current "one-size-fits-all" interventions.

Exploring the relationship between periodontal disease and pregnancy complications.

BACKGROUND: Increasing evidence suggests that maternal gingivitis and periodontitis may be a risk factor for preterm birth and other adverse pregnancy outcomes. TYPES OF STUDIES REVIEWED: To clarify the possible mechanisms behind the association between periodontal disease and preterm delivery, the authors reviewed studies of the effect of infection with periodontal pathogens in animal models on pregnancy outcomes including fetal growth, placental structural abnormalities and neonatal health. After the first report, in 1996, of a potential association between maternal periodontal disease and delivery of a preterm/low-birth-weight infant in humans, many case control and prospective studies were published. This review summarizes these, as well as early studies involving periodontal intervention to reduce risk. RESULTS: Although there are some conflicting findings and potential problems regarding uncontrolled underlying risk factors, most of the clinical studies indicate a positive correlation between periodontal disease and preterm birth. Recent studies also have shown that there are microbiologic and immunological findings that strongly support the association. The studies indicate that periodontal infection can lead to placental-fetal exposure and, when coupled with a fetal inflammatory response, can lead to preterm delivery. Data from animal studies raise the possibility that maternal periodontal infections also may have adverse long-term effects on the infant's development. CLINICAL IMPLICATIONS: Education for patients and health care providers regarding the biological plausibility of the association and the potential risks is indicated, but there is insufficient evidence at this time for health care policy recommendations to provide maternal periodontal treatments for the purpose of reducing the risk of adverse pregnancy outcomes.