Can vitamins improve periodontal wound healing/regeneration?

Periodontitis is a complex inflammatory disorder of the tooth supporting structures, associated with microbial dysbiosis, and linked to a number if systemic conditions. Untreated it can result in an irreversible damage to the periodontal structures and eventually teeth loss. Regeneration of the lost periodontium requires an orchestration of a number of biological events on cellular and molecular level. In this context, a set of vitamins have been advocated, relying their beneficial physiological effects, to endorse the biological regenerative events of the periodontium on cellular and molecular levels. The aim of the present article is to elaborate on the question whether or not vitamins improve wound healing/regeneration, summarizing the current evidence from in vitro, animal and clinical studies, thereby shedding light on the knowledge gap in this field and highlighting future research needs. Although the present review demonstrates the current heterogeneity in the available evidence and knowledge gaps, findings suggest that vitamins, especially A, B, E, and CoQ10 , as well as vitamin combinations, could exert positive attributes on the periodontal outcomes in adjunct to surgical or nonsurgical periodontal therapy.

A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis.

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. The disease is characterized by destruction of the alveolar bone due to an aberrant host inflammatory response to a dysbiotic oral microbiome. Previous genome-wide association studies (GWAS) have reported several suggestive susceptibility loci. Here, we conducted a GWAS using a German and Dutch case-control sample of aggressive periodontitis (AgP, 896 cases, 7,104 controls), a rare but highly severe and early-onset form of periodontitis, validated the associations in a German sample of severe forms of the more moderate phenotype chronic periodontitis (CP) (993 cases, 1,419 controls). Positive findings were replicated in a Turkish sample of AgP (223 cases, 564 controls). A locus at SIGLEC5 (sialic acid binding Ig-like lectin 5) and a chromosomal region downstream of the DEFA1A3 locus (defensin alpha 1-3) showed association with both disease phenotypes and were associated with periodontitis at a genome-wide significance level in the pooled samples, with P = 1.09E-08 (rs4284742,-G; OR = 1.34, 95% CI = 1.21-1.48) and P = 5.48E-10 (rs2738058,-T; OR = 1.28, 95% CI = 1.18-1.38), respectively. SIGLEC5 is expressed in various myeloid immune cells and classified as an inhibitory receptor with the potential to mediate tyrosine phosphatases SHP-1/-2 dependent signaling. Alpha defensins are antimicrobial peptides with expression in neutrophils and mucosal surfaces and a role in phagocyte-mediated host defense. This study identifies the first shared genetic risk loci of AgP and CP with genome-wide significance and highlights the role of innate and adaptive immunity in the etiology of periodontitis.

A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis.

AIM: The intronic variant rs4252120 in the plasminogen gene (PLG) is known to be associated with aggressive periodontitis (AgP) and atherosclerosis. Here, we examined the chromosomal region spanning PLG for associations with both chronic periodontitis (CP) and AgP. MATERIALS AND METHODS: The association of PLG candidate rs4252120 was tested in a German case-control sample of 1,419 CP cases using the genotyping assay hCV11225947 and 4,562 controls, genotyped with HumanOmni BeadChips. The German and Dutch sample of AgP cases (N = 851) and controls (N = 6,836) were genotyped with HumanOmni BeadChips. The North American CP sample (N = 2,681 cases, 1,823 controls) was previously genotyped on the Genome-Wide Human SNP Array 6.0. Genotypes were imputed (software Impute v2), and association tests were performed using an additive genetic model adjusting for sex and smoking. RESULTS: Rs4252120 was not associated with CP. However, a haplotype block downstream of PLG and not in linkage disequilibrium with rs4252120 (r2  = .08) was associated with both AgP (rs1247559; p = .002, odds ratio [OR] = 1.33) and CP (p = .02, OR = 1.15). That locus was also significantly associated with PLG expression in osteoblasts (p = 6.9 × 10-5 ). CONCLUSIONS: Our findings support a role of genetic variants in PLG in the aetiology of periodontitis.

Primary prevention of periodontitis: managing gingivitis.

UNLABELLED: Periodontitis is a ubiquitous and irreversible inflammatory condition and represents a significant public health burden. Severe periodontitis affects over 11% of adults, is a major cause of tooth loss impacting negatively upon speech, nutrition, quality of life and self-esteem, and has systemic inflammatory consequences. Periodontitis is preventable and treatment leads to reduced rates of tooth loss and improved quality of life. However, successful treatment necessitates behaviour change in patients to address lifestyle risk factors (e.g. smoking) and, most importantly, to attain and sustain high standards of daily plaque removal, lifelong. While mechanical plaque removal remains the bedrock of successful periodontal disease management, in high-risk patients it appears that the critical threshold for plaque accumulation to trigger periodontitis is low, and such patients may benefit from adjunctive agents for primary prevention of periodontitis. AIM: The aims of this working group were to systematically review the evidence for primary prevention of periodontitis by preventing gingivitis via four approaches: 1) the efficacy of mechanical self-administered plaque control regimes; 2) the efficacy of self-administered inter-dental mechanical plaque control; 3) the efficacy of adjunctive chemical plaque control; and 4) anti-inflammatory (sole or adjunctive) approaches. METHODS: Two meta-reviews (mechanical plaque removal) and two traditional systematic reviews (chemical plaque control/anti-inflammatory agents) formed the basis of this consensus. RESULTS: Data support the belief that professionally administered plaque control significantly improves gingival inflammation and lowers plaque scores, with some evidence that reinforcement of oral hygiene provides further benefit. Re-chargeable power toothbrushes provide small but statistically significant additional reductions in gingival inflammation and plaque levels. Flossing cannot be recommended other than for sites of gingival and periodontal health, where inter-dental brushes (IDBs) will not pass through the interproximal area without trauma. Otherwise, IDBs are the device of choice for interproximal plaque removal. Use of local or systemic anti-inflammatory agents in the management of gingivitis has no robust evidence base. We support the almost universal recommendations that all people should brush their teeth twice a day for at least 2 min. with fluoridated dentifrice. Expert opinion is that for periodontitis patients 2 min. is likely to be insufficient, especially when considering the need for additional use of inter-dental cleaning devices. In patients with gingivitis once daily inter-dental cleaning is recommended and the adjunctive use of chemical plaque control agents offers advantages in this group.

SLC23A1 polymorphism rs6596473 in the vitamin C transporter SVCT1 is associated with aggressive periodontitis.

AIM: Identification of variants within genes SLC23A1 and SLC23A2 coding for vitamin C transporter proteins associated with aggressive (AgP) and chronic periodontitis (CP). MATERIAL AND METHODS: Employment of three independent case-control samples of AgP (I. 283 cases, 979 controls; II. 417 cases, 1912 controls; III. 164 cases, 357 controls) and one sample of CP (1359 cases, 1296 controls). RESULTS: Stage 1: Among the tested single-nucleotide polymorphisms (SNPs), the rare allele (RA) of rs6596473 in SLC23A1 showed nominal significant association with AgP (p = 0.026, odds ratio [OR] 1.26, and a highly similar minor allele frequency between different control panels. Stage 2: rs6596473 showed no significant association with AgP in the replication with the German and Dutch case-control samples. After pooling the German AgP populations (674 cases, 2891 controls) to significantly increase the statistical power (SP = 0.81), rs6596473 RA showed significant association with AgP prior to and upon adjustment with the covariates smoking and gender with padj  = 0.005, OR = 1.35. Stage 3: RA of rs6596473 showed no significant association with severe CP. CONCLUSION: SNP rs6596473 of SLC23A1 is suggested to be associated with AgP. These results add to previous reports that vitamin C plays a role in the pathogenesis of periodontitis.

Validation of reported genetic risk factors for periodontitis in a large-scale replication study.

AIM: Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). MATERIAL AND METHODS: We analysed 23 genes in 600 German AgP patients and 1441 controls on the Illumina custom genotyping array Immunochip. We tested a suggestive association in a Dutch and German/Austrian AgP case-control sample, and a German chronic periodontitis (CP) case-control sample using Sequenom iPlex assays. We additionally tested the common known risk variant rs1333048 of the gene ANRIL for its association in a Turkish and Italian population. RESULTS: None of the analysed genes gave statistical evidence for association. Upon covariate adjustment for smoking and gender, in the pooled German-Austrian AgP sample, IL10 SNP rs6667202 was associated with p = 0.016, OR = 0.77 (95% CI = 0.6-0.95), and in the Dutch AgP sample, adjacent IL10 SNP rs61815643 was associated with p = 0.0009, OR = 2.31 (95% CI = 1.4-3.8). At rs61815643, binding of the transcription factor PPARG was predicted. ANRIL rs1333048 was associated in the Turkish sample (pallelic = 0.026, OR = 1.67 [95% CI = 1.11-2.60]). CONCLUSIONS: Previous candidate genes carry no susceptibility factors for AgP. Association of IL-10 rs61815643 with AgP is suggested. ANRIL is associated with periodontitis across different populations.

Proximal contact tightness between direct-composite additions in the posterior dentition: an in vitro investigation.

PURPOSE: The aim of the study was to test whether a novel three-step matrix technique for posterior direct-composite additions creates sufficiently strong proximal contacts. MATERIALS AND METHODS: Contact tightness was measured between direct-composite additions and between original teeth on a model. Therefore, the frictional forces required to remove a straight, 0.05-mm-thick, metal matrix band inserted between adjacent teeth and held by a universal testing machine (Zwicki, Zwick GmbH, Ulm, Germany) were recorded. Measurements were taken at three time points to carry out reference analysis: at baseline, after removal of the maxillary right second premolar (tooth #15) to simulate a diastema, and after closure of the diastema by inserting two direct-composite additions with the three-step matrix technique on the maxillary right first premolar (tooth #14) and first molar (tooth #16). Measurements were performed in the maxillary right (first) and left (second) quadrants to document sagittal displacement. RESULTS: The original contact tightness values were between 1.65 ± 0.88 N and 3.05 ± 0.60 N in the first quadrant and between 1.23 ± 0.51 N and 2.18 ± 0.43 N in the second quadrant. After removal of tooth 15, values decreased significantly in the first quadrant and insignificantly in the second. After reconstruction, the contact tightness between teeth 14 and 16 was significantly stronger (tighter) (3.20 ± 0.80 N) than the originally measured contact tightness between teeth 14 and 15 (2.86 ± 0.64 N) and teeth 15 and 16 (1.65 ± 0.88 N) (p=0.006 and 0.001, respectively). CONCLUSIONS: Within the limitations of an in vitro investigation, this study has shown that by using a novel, three-step matrix technique, direct posterior composite additions can form sufficiently tight proximal contacts.

Attitude of Midwives towards Fluoride Recommendations and Oral Prevention in Infants and Young Children.

Early childhood caries is a challenge. Early dental screening flanked by multidisciplinary preventions by pediatricians, dentists, and midwives (MWs) may be helpful. New recommendations for dental screening in children (FUs) and fluoride have been introduced in Germany. The aim of this study was to investigate whether midwives consider FUs useful and implement early childhood caries prevention, as well as fluoride recommendations. The survey was conducted using an online questionnaire. Demographic data, including 11 items on early childhood dental prophylaxis and fluoride, were requested. Agreement was recorded using Likert scales. The data were analyzed descriptively. Two hundred and seventeen female MWs participated (age: 44.1 (11.04) years). One hundred and four (47.9%) participants knew about the FUs. Of the MWs, 30.7% found a referral from the first tooth to be very important (important/neutral/unimportant: 27%/27.9%/14.4%), compared with 84.8% for the entire primary dentition (11.8%/2.8%/0.5%). Of the MWs, 41.7% always recommended fluoride toothpaste from the first tooth (often/occasionally/rarely/never: 22.7%/12.4%/7.9%/15.3%) and 48.1% completely rejected fluoride-free toothpaste (always/often/occasionally/rarely: 9.8%/8.9%/17.3%/15.9%). In addition, 54.8% never recommended the use of fluoride tablets (always/often/occasionally/rarely: 9.2%/7.4%/10.2%/18.4%). The FUs are not yet well-known among MWs, and only less than one-third recommended dental check-ups, starting with the first tooth. This contrasts with the high uptake of fluoridated toothpaste. More educational work should be carried out to convince more MWs of the benefits of the FUs.

Are the Dental Guidelines for Early Dental Visits and Fluoridation Measures Supported by Pediatricians, and What Are Their Caries Prevention Efforts?

(1) Background: In Germany, new recommendations for dental examinations of children and the use of fluorides have been introduced. The pediatrician (PA) should refer the patient to the dentist for dental examinations and check-ups (DEs) from the sixth month of age. Therefore, our aim was to determine with a questionnaire the extent to which PAs find DE useful, make referrals for DE and recommend fluoride. (2) Methods: The nationwide empirical survey was conducted with a self-developed and validated standardized online questionnaire. In addition to personal information, 16 items were collected. Agreement with the items was recorded using Likert scales. The data were primarily analysed descriptively. (3) Results: 696 PAs participated in the survey (age: 51.7 (8.4) years, women/men: 428/286 (61.5/38.5%). A total of 11% of PAs found referral by eruption of first tooth very important (important/neutral/unimportant: 13.8/32/43.2%), compared to 70% for complete deciduous teeth (21.3/7.3/1.4%). A total of 48.8% of PAs always recommended fluoridated toothpaste from the first tooth (often/occasionally/rarely/never: 18.3/7.8/8/17.1%) and 50.6% completely refused to recommend fluoride-free toothpaste (always/often/occasionally/rarely: 9.8/9/14.7/15.9%). A total of 44.8% never recommended the use of fluoridated toothpaste if the child cannot yet spit (always/often/occasionally/rarely: 19.2/13.9/7.8/14.3%). (4) Conclusions: Among PAs, referral to DEs was increasingly implemented as children grew older. Specific fluoride recommendations were accepted.

Shaping ability of four root canal instrumentation systems in simulated 3D-printed root canal models.

INTRODUCTION: The aim of this study was to compare the shaping ability of four root canal preparation systems in newly developed 3D-printed root canal models. MATERIALS AND METHODS: For this study, 1080 3D-printed acrylic resin blocks with nine different root canal configurations were produced. They were prepared with Reciproc R25 (#25), F6 SkyTaper (#25 and #30) F360 (#25 and #35) and One Shape (#25) (N = 30 per system). Pre- and post-instrumentation images were superimposed for evaluation of the centering ratio of the different systems. Ledges, instrument fractures and preparation times were also recorded. Analysis of variance (ANOVA) and post-hoc Tukey tests were conducted, comparing the mean canal centering ratios and the mean preparation times. RESULTS: There were significant differences between all systems regarding the centering ratios in the different root canal configurations (ANOVA p < 0.001). The root canal configuration had considerable effect on the centering ratio of the instruments. The best overall mean centering ratios were achieved with F6 SkyTaper #25 instruments especially in canal configurations with big curvature angles and radii, while F360 #35 was least centered especially in canals with small curvature angles and radii. Most ledges occurred with OneShape, while it was the significantly (p < 0.001) fastest preparation system (86.7 s (SD 13.53)) and Reciproc the significantly (p < 0.001) slowest (103.0 s (SD 20.67)). CONCLUSION: 3D-printed root canals are suitable to produce challenging canal configurations and to investigate the limitations of root canal instruments. We found that all instruments caused canal transportations. However, F6 SkyTaper #25 files had better overall centering ratios than the other instruments. In canal configurations with small curvature radii, the centering ratio of some instruments is low and the probability for ledges is increased.

Genetic evidence for PLASMINOGEN as a shared genetic risk factor of coronary artery disease and periodontitis.

BACKGROUND: Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms. METHODS AND RESULTS: In-depth genotyping of 46 published CAD risk loci of genome-wide significance in the worldwide largest case-control sample of the severe early-onset phenotype aggressive periodontitis (AgP) with the Illumina Immunochip (600 German AgP cases, 1448 controls) and the Affymetrix 500K array set (283 German AgP cases and 972 controls) highlighted ANRIL as the major risk gene and revealed further associations with AgP for the gene PLASMINOGEN (PLG; rs4252120: P=5.9×10(-5); odds ratio, 1.27; 95% confidence interval, 1.3-1.4 [adjusted for smoking and sex]; 818 cases; 5309 controls). Subsequent combined analyses of several genome-wide data sets of CAD and AgP suggested TGFBRAP1 to be associated with AgP (rs2679895: P=0.0016; odds ratio, 1.27 [95% confidence interval, 1.1-1.5]; 703 cases; 2.143 controls) and CAD (P=0.0003; odds ratio, 0.84 [95% confidence interval, 0.8-0.9]; n=4117 cases; 5824 controls). The study further provides evidence that in addition to PLG, the currently known shared susceptibility loci of CAD and periodontitis, ANRIL and CAMTA1/VAMP3, are subjected to transforming growth factor-ß regulation. CONCLUSIONS: PLG is the third replicated shared genetic risk factor of atherosclerosis and periodontitis. All known shared risk genes of CAD and periodontitis are members of transforming growth factor-ß signaling.