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A biologic is a therapeutic agent with biological activity that is administered to achieve an enhanced regenerative or reparative effect. The use of biologics has progressively become a core component of contemporary periodontal practice. However, some questions remain about their safety, indications, and effectiveness in specific clinical scenarios. Given their availability for routine clinical use and the existing amount of related evidence, the goal of this American Academy of Periodontology (AAP) best evidence consensus (BEC) was to provide a state-of-the-art, evidence-based perspective on the therapeutic application of autologous blood-derived products (ABPs), enamel matrix derivative (EMD), recombinant human platelet-derived growth factor BB (rhPDGF-BB), and recombinant human bone morphogenetic protein 2 (rhBMP-2). A panel of experts with extensive knowledge on the science and clinical application of biologics was convened. Three systematic reviews covering the areas of periodontal plastic surgery, treatment of infrabony defects, and alveolar ridge preservation/reconstruction and implant site development were conducted a priori and provided the foundation for the deliberations. The expert panel debated the merits of published data and exchanged experiential information to formulate evidence-based consensus statements and recommendations for clinical practice and future research. Based on an analysis of the current evidence and expert opinion, the panel concluded that the appropriate use of biologics in periodontal practice is generally safe and provides added benefits to conventional treatment approaches. However, therapeutic benefits and risks range based on the specific biologics used as well as patient-related local and systemic factors. Given the limited evidence available for some indications (e.g., gingival augmentation therapy, alveolar ridge preservation/reconstruction, and implant site development), future clinical studies that can expand the knowledge base on the clinical use of biologics in periodontal practice are warranted.

Introduction: On the topic of adjuncts to scaling and root planing (SRP), numerous randomized clinical trials (RCTs) were published by a single group of authors and frequently reported unusually large effect sizes. A meta-analysis in part 1 of this project failed to explain the causes for these unusual findings. We assessed the reporting quality and trial registration discrepancies to examine the possibility of replicating the work of this research group as well as the overall rigor of the research methodology. Methods: This study was preregistered at the Open Science Framework ( https://osf.io/4meyd/ ). The Scopus platform was utilized for the RCT search on SRP adjuncts in intrabony defects in patients with periodontitis as compared with SRP alone. The search analysis was limited from 2010 to 2017, and RCTs on SRP adjuncts published by a single research group were selected for screening and inclusion. RCT registration records were assessed for consistency. Results: Out of 92 studies that were retrieved from Scopus and PubMed, 32 were included for quality assessment per the CONSORT guidelines (Consolidated Standards of Reporting Trials). Results showed that all RCTs were characterized by a low reporting quality. The majority of CONSORT items scored Conclusion: RCTs by this group were characterized by poor adherence to reporting quality guidelines. Crucial RCT elements, such as randomization, blinding, and primary outcomes, were not reported properly. RCT registration records revealed systematic inconsistencies when compared with RCT publication. Therefore, the unusually large effects reported by this group should be viewed with extreme caution. Knowledge Transfer Statement: The included randomized clinical trials were characterized by poor adherence to reporting quality guidelines, missing information about important trial items, and discrepancies between the reports and trial registrations. This quality assessment should guide clinical research and show clinicians that they should be cautious when applying evidence in their clinical practice.

Background: A number of studies in patients with periodontitis have compared scaling and root planning (SRP) combined with an adjunctive treatment to SRP alone. Within that literature, an array of studies with overlapping investigators has consistently yielded substantially greater effects of adjunctive treatments than had been previously noted. This report investigates discrepancies between that cluster of research and the most recent American Dental Association (ADA) systematic review. Methods: This review was preregistered at https://osf.io/4meyd/ . A search using the Scopus platform identified 32 articles published from 2010 to 2017 by investigators affiliated with the Government Dental College and Research Institute (GDCRI) in Bangalore, India. The primary outcome used in this meta-analysis was the change in clinical attachment level (CAL) after 6 mo. Effect sizes were estimated using Comprehensive Meta-Analysis software after categorizing agents into groups based on pharmacologic similarity. Results: The search identified 32 studies encompassing 5 sets of adjunctive agents. Across the GDCRI studies, the CAL averaged 1.67 mm (95% confidence interval [CI]: 1.43–1.91 mm), substantially exceeding values reported in the ADA review (mean: 0.39 mm, 95% CI: 0.27–0.51 mm). For categories of studies in which comparable subgroup estimates were available, the evaluations yielded overlapping estimates of SRP alone, but CAL estimates were discrepant for both locally delivered antimicrobials (GDCRI studies: mean: 1.45 mm, 95% CI: 0.63–2.27 mm; ADA review: mean: 0.38 mm, 95% CI: 0.16 –0.60 mm) and systemic antibiotics (GDCRI studies: mean: 1.35 mm, 95% CI: 0.97–1.73 mm; ADA review: mean: 0.39 mm, 95% CI: 0.21–0.57 mm). Conclusion: In the literature on adjunctive agents supplementing SRP, findings from investigators linked to GDCRI stand out as having significantly more favorable estimated effects. Meanwhile, some agents studied by GDCRI-linked investigators have not been investigated by other researchers. In the absence of a clear explanation for discrepant results, it is recommended that unusually favorable reported effects of adjunctive agents be viewed with caution. Knowledge Transfer Statement: The present meta-analysis observed an unusually large effect size of adjunctive agents to scaling and root planning in studies conducted by the same research group. These results were not consistent with trials on adjunctive agents and previous reports. As this research group has exclusively tested most of the agents, their results must be viewed with caution until other independent groups replicate the studies and reproduce the effect size.

ObjectivePoor reporting in randomized clinical trial (RCT) abstracts reduces quality and misinforms readers. Spin, a biased presentation of findings, could frequently mislead clinicians to accept a clinical intervention despite non-significant primary outcome. Therefore, good reporting practices and absence of spin enhances research quality. We aim to assess the reporting quality and spin in abstracts of RCTs evaluating the effect of periodontal therapy on cardiovascular (CVD) outcomes.MethodsPubMed, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), and 17 trial registration platforms were searched. Cohort, non-randomized, non-English studies, and pediatric studies were excluded. RCT abstracts were reviewed by 2 authors using the CONSORT for abstracts and spin checklists for data extraction. Cohen's Kappa statistic was used to assess inter-rater agreement. Data on the selected RCT publication metrics were collected. Descriptive analysis was performed with non-parametric methods. Correlation analysis between quality, spin and bibliometric parameters was conducted.Results24 RCTs were selected for CONSORT analysis and 14 fulfilled the criteria for spin analysis. Several important RCT elements per CONSORT were neglected in the abstract including description of the study population (100%), explicitly stated primary outcome (87%), methods of randomization and blinding (100%), trial registration (87%). No RCT examined true outcomes (CVD events). A significant fraction of the abstracts appeared with at least one form of spin in the results and conclusions (86%) and claimed some treatment benefit in spite of non-significant primary outcome (64%). High-quality reporting had a significant positive correlation with reporting of trial registration (p = 0.04) and funding (p = 0.009). Spinning showed marginal negative correlation with reporting quality (p = 0.059).ConclusionPoor adherence to the CONSORT guidelines and high levels of data spin were found in abstracts of RCTs exploring the effects of periodontal therapy on CVD outcomes. Our findings indicate that journal editors and reviewers should consider strict adherence to proper reporting guidelines to improve reporting quality and reduce waste.

Background Standard recommendations for oral hygiene practices have focused on mechanical methods (toothbrushing and interdental cleaning). Published evidence indicates antimicrobial mouthrinses provide oral health benefits beyond mechanical methods alone. The purpose of this meta-analysis was to evaluate the combined effectiveness of mechanical methods with essential oil–containing mouthrinses (MMEO) versus mechanical methods (MM) alone in achieving site-specific, healthy gingival tissue and reducing plaque and gingivitis. Types of Studies Reviewed All industry-sponsored clinical trials investigating the antigingivitis and antiplaque effects of essential oil (EO)–containing mouthrinses conducted from 1980 to 2012 were reviewed; 29 of 32 studies met the inclusion criteria of 6 months or longer duration, randomized, observer-masked, placebo-controlled, and with individual-level site-specific data. By-study treatment effects were estimated through generalized linear models for binary data and analysis of covariance for continuous data, and then combined using standard meta-analysis techniques; heterogeneity was also assessed. Results Summary odds ratios for a healthy gingival site and for a plaque-free site were, respectively, 5.0 (95% confidence interval [CI], 3.3-7.5) and 7.8 (95% CI, 5.4-11.2) for MMEO participants versus MM participants at 6 months. The summary percentage reductions in whole-mouth mean gingivitis and plaque at 6 months were 16.0 (95% CI, 11.3-20.7) and 27.7 (95% CI, 22.4-32.9), respectively. Responder analyses using aggregate individual-level data showed 44.8% of MMEO participants and 14.4% of MM participants achieved at least 50% healthy sites in their mouths at 6 months. Similarly, 36.9% of MMEO participants and 5.5% of MM participants achieved at least 50% plaque-free sites in their mouths at 6 months. Conclusions and Practical Implications This is the first meta-analysis to demonstrate the clinically significant, site-specific benefit of adjunctive EO treatment in people within a 6-month period (that is, between dental visits).

Smile esthetics have been shown to play a major role in the perception of whether a person is attractive, and whether they are perceived as friendly, trustworthy, intelligent, and self-confident. A proposed major determinant of the esthetics of a smile is the amount of gingival display, which can be excessive in cases of altered passive eruption. The aim of this study is to see whether altering the amount of gingival display of patients would affect dental professionals' and laypersons' perceptions of the aforementioned social parameters.Patients were identified as having altered passive eruption and excessive gingival display. Smiling "control" photographs were taken and then digitally altered so as to lengthen the teeth and thus reduce the amount of gingival display. These became the "test" photographs. The control and test photographs were shown in random order. The control group of evaluators consisted of senior dental students, and the test group of evaluators comprised students who had no formal dental training. Groups were asked to rate, on a visual analog scale, each picture's attractiveness, friendliness, trustworthiness, intelligence, and self-confidence.The test pictures with less gingival display were consistently and statistically significantly rated higher for all five social parameters than were their control counterparts (P0.0001). When analyzed as an isolated effect, there were no statistically significant differences between the control group and the test group of evaluators when rating the pictures. Pictures depicting African Americans were judged to be more trustworthy (P = 0.0467) and self-confident (P = 0.0490) than pictures depicting white individuals. Pictures depicting women were judged to be more trustworthy (P = 0.0159) and intelligent (P = 0.0329) than pictures depicting men. All the social parameters were positively and statistically significantly correlated with each other (P0.0001).Excessive gingival display did negatively affect how attractive a person's smile is judged to be. In addition, how friendly, trustworthy, intelligent, and self-confident a person was perceived to be was inversely related to the amount of gingival display. Untrained laypeople were just as sensitive to these differences as senior dental students.

Although brief alcohol interventions have proven effective in a variety of health care settings, the present article describes the development of the first brief intervention for heavy drinkers in dental practice. Elements of motivational interviewing and personalized normative feedback were incorporated in a 3- to 5-minute intervention delivered by dental hygienists. The intervention is guided by a one-page feedback report providing personalized normative feedback regarding the patient’s current oral health practices, their drinking in comparison to others, and oral cancer risk associated with current smoking and drinking. Future publications will present data regarding intervention effectiveness from an ongoing randomized trial.

It was hypothesized that if periodontal infections predispose low birth weights and premature birth, then such outcomes should be apparent when the mother has aggressive periodontitis (AgP).Birth weight data were collected by questionnaire from females with AgP, their periodontally healthy siblings, and unrelated periodontally healthy women. Both prospective and retrospective birth outcome data were used. Because many of the periodontal evaluations were performed after the births, there were incomplete data regarding most of the risk factors for low birth weight. We determined associations between mothers' periodontal diagnoses and clinical variables and the reported birth weights.There were no significant differences in mean birth weights of babies born to control subjects or AgP patients. This was true whether all the births were considered or only those reported1 or 2 years before periodontal examination. For periodontally healthy controls, 13.2% of babies born to siblings of AgP patients and 12.8% of babies born to unrelated mothers weighed2,500 g, whereas 9.9% of those born to mothers with generalized AgP and 10.3% of those born to mothers with localized AgP weighed2,500 g.Because of the relative rarity of AgP in the population, and attendant difficulties in performing a prospective study of its association with pregnancy outcomes, we used a compromised approach using prospective data as well as weaker retrospective data assuming that disease onset was likely before the births. Our results, within the limitations of this approach, indicate no evidence that AgP in the mother predisposes low birth weights. AgP has many unique biologic characteristics that differentiate it from chronic forms of periodontal disease, and the possible lack of its association with birth weight may be another such characteristic.

This study compared faculty perceptions and expectations of dental students' abilities using virtual reality simulation (VRS) to those who did not use virtual reality simulation (non-VRS) in an operative dentistry preclinical course. A sixteen-item survey with a ten-point rating scale and three open-ended questions asked about students' abilities in ergonomics, confidence level, performance, preparation, and self-assessment. The surveys were administered three times to a small group of preclinical faculty members. First, faculty members (n=12, 92 percent response rate) gave their perceptions of non-VRS students' abilities at the end of their traditional course. Secondly, faculty members (n=13, 100 percent response rate) gave their expectations of the next incoming class's abilities (VRS students) prior to the start of the course with traditional and VRS components. Finally, faculty members (n=13, 100 percent response rate) gave their perceptions of VRS students' abilities after completion of the course. A Tukey's test for multiple comparisons measured significance among survey items. Faculty perceptions of VRS students' abilities were higher than for non-VRS students for most abilities examined. However, the faculty members' expectations of VRS training were higher than their perceptions of the students' abilities after VRS training for most abilities examined. Since ergonomic development and technical performance were positively impacted by VRS training, these results support the use of VRS in a preclinical dental curriculum.

The purpose of this study was to compare the performance of students exposed to two different instructional modalities for dental anatomy wax carving: CAI (computer-assisted instruction) using DVD technology, or traditional laboratory instruction. Students' self-assessment scores were also compared to faculty scores, and students' perceptions of their teaching modality were analyzed. Seventy-three first-year dental students (response rate 81 percent) participated in this randomized single blind trial, in which faculty graders were blinded to student group assignment. There were no statistical differences, as determined by the Wilcoxon non-parametric test and a t-test, between the faculty grades on the wax carving from the two teaching methods the students experienced. The student self-assessments revealed higher mean grades (3.0 for the DVD-only group and 3.1 for the traditional group) than the faculty actual mean grades (2.2 for both the DVD-only group and the traditional group) by almost one grade level on a 4.0 grade scale. Similar percentages of students in the traditional group had either favorable or unfavorable perceptions of their learning experience, while more students in the DVD-only group reported favorable perceptions. Students from both groups said they wanted more faculty feedback in the course. Based on these objective and subjective data, merging CAI and traditional laboratory teaching may best enhance student learning needs.

Low-calorie diets are commonplace for reducing body weight. However, no information is available on the effects of a reduced-calorie diet on periodontal inflammation and disease. The purpose of this study was to evaluate the clinical effects of a long-term calorie-restriction (CR) diet on periodontitis in an animal model of periodontitis.Periodontitis was induced in 55 young, healthy, adult rhesus monkeys (Macaca mulatta) by tying 2.0 silk ligatures at the gingival margins of maxillary premolar/molar teeth. Animals on a CR diet (30% CR; N = 23) were compared to ad libitum diet controls (N = 32). Clinical measures, including the plaque index (PI), probing depth (PD), clinical attachment level (CAL), modified gingival index (GI), and bleeding on probing (BOP) were recorded at baseline and 1, 2, and 3 months after ligature placement.Significant effects of CR were observed on the development of inflammation and the progression of periodontal destruction in this model. Compared to controls, CR resulted in a significant reduction in ligature-induced GI (P0.0001), BOP (P0.0015), PD (P0.0016), and CAL (P0.0038). Periodontal destruction, as measured by CAL, progressed significantly more slowly in the CR animals than in the controls (P0.001).These clinical findings are consistent with available evidence that CR has anti-inflammatory effects. Moreover, these experimental findings are the first observations, to the best of our knowledge, that CR dampens the inflammatory response and reduces active periodontal breakdown associated with an acute microbial challenge.

Background and Methods The author conducted a systematic review of the literature to evaluate the efficacy of antigingivitis and antiplaque products in six-month trials. He searched electronic databases for six-month randomized clinical studies that evaluated both antiplaque and antigingivitis properties of dentifrices or mouthrinses. In addition, the author solicited unpublished studies from manufacturers. Results Seventeen studies support the antiplaque, antigingivitis effects of dentifrices containing 0.30 percent triclosan, 2.0 percent Gantrez copolymer. There was no evidence of efficacy for triclosan products containing either soluble pyrophosphate or zinc citrate. Dentifrices with stannous fluoride had statistically significant, but marginally clinically significant, evidence of an antiplaque effect; however, there was both a statistically and clinically significant antigingivitis effect. The largest body of studies (21 studies) supported the efficacy of mouthrinses with essential oils. A smaller body of studies (seven) supported a strong antiplaque, antigingivitis effect of mouthrinses with 0.12 percent chlorhexidine. Results for mouthrinses with cetylpyridinium chloride varied and depended on the product's formula. Conclusions The studies in this systematic review provide strong evidence of the antiplaque, antigingivitis effects of multiple agents. These results support the use of these agents as part of a typical oral hygiene regimen.

Previous surgical crown lengthening studies have investigated positional changes of the free gingival margin but not the biological width. Histological studies utilizing animal models have shown that postoperative crestal resorption allowed reestablishment of the biological width. However, very little work has been done in humans. Therefore, the purpose of this study was to evaluate the positional changes of the periodontal tissues, particularly the biological width, following surgical crown lengthening in human subjects.Twenty-three (23) patients who needed surgical crown lengthening to gain retention necessary for prosthetic treatment and/or to access caries, tooth fracture, or previous prosthetic margins entered the study. The following parameters were obtained from line angles of treated teeth (teeth requiring surgical crown lengthening) and adjacent teeth with adjacent and non-adjacent sites: plaque and gingival indexes, free gingival margin, probing depth, attachment level, bone level, direct bone level, and biological width. During surgery, the bone level was reduced based on the future prosthetic margin and predetermined biological width; flaps were placed at the bony crest. Patients were examined at baseline and at 3 and 6 months postoperatively.Eighteen patients completed the study. Overall, the amount of bone resected was 1 to 5 mm. At 90% of treated sites,or = 3 mm of bone was removed. At 3 months, the apical displacement of the free gingival margin at non-adjacent, adjacent, and treated sites was 2.46 +/- 0.25 mm, 2.68 +/- 0.20 mm, and 3.07 +/- 0.16 mm, respectively. There was no significant change in the position of the free gingival margin from 3 to 6 months. The biological width at all sites was smaller at 3 and 6 months compared to baseline (P0.05) except for the treated sites, which were not significantly different from baseline at 6 months.During surgical crown lengthening, the bone level was lowered for placement of the prosthetic margin and reestablishment of the biological width. The biological width, at treated sites, was reestablished to its original vertical dimension by 6 months. In addition, a consistent 3 mm gain of coronal tooth structure was observed at the 3- and 6-month examinations.

Oral diseases including periodontal disease and caries are some of the most prevalent infectious diseases in humans. Different microbial species cohabitate and form a polymicrobial biofilm called dental plaque in the oral cavity. Metagenomics using next generation sequencing technologies has produced bacterial profiles and genomic profiles to study the relationships between microbial diversity, genetic variation, and oral diseases. Several oral metagenomic studies have examined the oral microbiome of periodontal disease and caries. Gene annotations in these studies support the association of specific genes or metabolic pathways with oral health and with specific diseases. The roles of pathogenic species and functions of specific genes in oral disease development have been recognized by metagenomic analysis. A model is proposed in which three levels of interactions occur in the oral microbiome that determines oral health or disease.

Human immunoglobulin G2 (IgG2) serum concentrations and the IgG2 antibody response to Actinobacillus actinomycetemcomitans can be influenced by genes, by environmental factors such as smoking, and by periodontal disease status. Examination of the IgG2 response to phosphorylcholine (PC), a response thought to be mainly induced by the C polysaccharide of Streptococcus pneumoniae , suggested that periodontal disease status was also associated with this response. This prompted the hypothesis that PC is an important oral antigen associated with organisms in the periodontal flora and that anti-PC antibody is elevated as a consequence of periodontal disease. Subjects in various periodontal disease diagnostic categories in which attachment loss is exhibited were tested for anti-PC in serum. Those with adult periodontitis, localized juvenile periodontitis, generalized early-onset periodontitis, and gingival recession all had similar levels of anti-PC IgG2 serum antibody which were significantly greater than in the group of subjects with no attachment loss. Analysis of plaque samples from subgingival and supragingival sites in all diseases categories for reactivity with the anti-PC specific monoclonal antibody TEPC-15 revealed that a substantial proportion of the bacteria in dental plaque (30 to 40%) bear PC antigen; this antigen was not restricted to morphotypes resembling only cocci but was also present on rods and branched filamentous organisms. We found that S. mitis , S. oralis , and S. sanguis , as well as oral actinomycetes, including A. viscosus , A. odontolyticus , and A. israelii , incorporated substantial amounts of [ 3 H]choline from culture media. Further analysis of antigens derived from these organisms by Western blot indicated that S. oralis , S. sanguis , A. viscosus , A. odontolyticus , and A. israelii contained TEPC-15-reactive antigens. The data show that many commonly occurring bacterial species found in dental plaque contain PC antigen and that immunization with plaque-derived PC antigens as a consequence of inflammation and periodontal attachment loss may influence systemic anti-PC antibody concentrations.

We examined the subgingival bacterial biodiversity in untreated chronic periodontitis patients by sequencing 16S rRNA genes. The primary purpose of the study was to compare the oral microbiome in deep (diseased) and shallow (healthy) sites. A secondary purpose was to evaluate the influences of smoking, race and dental caries on this relationship. A total of 88 subjects from two clinics were recruited. Paired subgingival plaque samples were taken from each subject, one from a probing site depth >5 mm (deep site) and the other from a probing site depth ≤3mm (shallow site). A universal primer set was designed to amplify the V4-V6 region for oral microbial 16S rRNA sequences. Differences in genera and species attributable to deep and shallow sites were determined by statistical analysis using a two-part model and false discovery rate. Fifty-one of 170 genera and 200 of 746 species were found significantly different in abundances between shallow and deep sites. Besides previously identified periodontal disease-associated bacterial species, additional species were found markedly changed in diseased sites. Cluster analysis revealed that the microbiome difference between deep and shallow sites was influenced by patient-level effects such as clinic location, race and smoking. The differences between clinic locations may be influenced by racial distribution, in that all of the African Americans subjects were seen at the same clinic. Our results suggested that there were influences from the microbiome for caries and periodontal disease and these influences are independent.

Aim: The aim of this review was to critically appraise the evidence on the impact of periodontal treatment of cardiovascular diseases (CVDs) biomarkers and outcomes. Methods: A systematic search was performed in Cinhal, Cochrane, Embase and Medline for relevant articles up to July 2012. Duplicate screening and reference hand searching were performed. Data were then summarized and evidence graded in tables. Results: The search resulted in: (a) no evidence on the effects of periodontal therapy on subclinical atherosclerosis, serum levels of CD40 ligand, serum amyloid A and monocyte chemoattractant protein-1, (b) limited evidence on the effects of periodontal therapy on arterial blood pressure, leucocyte counts, fibrinogen, tissue necrosis factor-a, sE-selectin, von Willebrand factors, d-dimers, matrix metalloproteinases, oxidative stress and CVD events, and (c) moderate evidence suggesting a negligible effect of periodontal therapy in reducing interleukin-6 and lipids levels, whilst a positive effect in reducing serum C-reactive protein levels and improving endothelial function. Conclusions: Periodontal therapy triggers a short-term inflammatory response followed by (a) a progressive and consistent reduction of systemic inflammation and (b) an improvement in endothelial function. There is however limited evidence that these acute and chronic changes will either increase or reduce CVD burden of individuals suffering from periodontitis in the long term.

Patients with localized juvenile periodontitis (LJP) often have high titers of antibody reactive with the serotype-specific immunodominant carbohydrate antigen of Actinobacillus actinomycetemcomitans serotype b. The vast majority of this A. actinomycetemcomitans serotype b-specific antibody is immunoglobulin G2 (IgG2). The present study was undertaken to determine whether the overall total levels of IgG2 in the sera of LJP patients are elevated. LJP patients and nonperiodontitis (NP) controls matched for age, race (black and white), and gender were studied. Additional controls included patients with adult periodontitis (AP) and patients similar in age to LJP patients but with the more-severe, generalized form of early-onset periodontitis (SP). Sera from over 700 periodontally characterized subjects were examined by using radial immunodiffusion to quantitate IgG2 as well as IgG1, -3, and -4, which were included for comparison. Serum IgG2 levels increased with age, and this was most dramatic around puberty. Black subjects in all periodontal groups had nearly 1 mg more IgG2 per ml than their white counterparts. Serum IgG2 levels were elevated (about 30 to 40%) in LJP patients of both races compared with their age- and race-matched NP controls (P < 0.01). In contrast, SP patients and AP patients had IgG2 levels comparable to their age- and race-matched NP controls. No other IgG subclass concentration correlated with periodontal diagnosis except for IgG3, which was elevated in white LJP patients. We reason that the high levels of serum IgG2 in LJP may be helpful in localizing periodontal destruction.

Background- In the Periodontitis and Vascular Events (PAVE) pilot study periodontal therapy was provided as an intervention in a secondary cardiac event prevention model through five coordinated cardiac-dental centers. Methods- Subjects were randomized to either community care or protocol provided scaling and root planing to evaluate effects on periodontal status and systemic levels of high-sensitivity Creactive protein (hs-CRP). Results- After 6 months there was a significant reduction in mean probing depth and extent of 4- or 5-mm pockets. However there were no significant differences in attachment levels bleeding upon probing or extent of subgingival calculus comparing subjects assigned to protocol therapy (n = 151) to those assigned to community care (n = 152). Using intent-to-treat analyses there was no significant effect on serum hs-CRP levels at 6 months. However 48% of the subjects randomized to community care received preventive or periodontal treatments. Secondary analyses demonstrated that consideration of any preventive or periodontal care (i.e. any treatment) compared to no treatment showed a significant reduction in the percentage of people with elevated hs-CRP (values >3 mg/l)at 6 months. However obesity nullified the periodontal treatment effects on hs-CRP reduction. The adjusted odds ratio for hs-CRP levels >3 mg/l at 6 months for any treatment versus no treatment among non-obese individuals was 0.26 (95%confidence interval: 0.09 to 0.72) adjusting for smoking marital status and gender. Conclusion- This pilot study demonstrated the critical role of considering obesity as well as rigorous preventive and periodontal care in trials designed to reduce cardiovascular risk. Originally published Journal of Periodontology Vol. 80 No. 2 Feb 2009

Dietary caloric restriction (CR) has been found to reduce systemic markers of inflammation and may attenuate the effects of chronic inflammatory conditions. The purpose of this study was to examine the effects of long-term CR on naturally occurring chronic inflammatory periodontal disease in a nonhuman primate model.The effects of long-term CR on extent and severity of naturally occurring chronic periodontal disease, local inflammatory and immune responses, and periodontal microbiology, were evaluated in a cohort of 81 (35 female and 46 male; 13-40 y of age) rhesus monkeys (Macaca mulatta) with no previous exposure to routine oral hygiene. CR monkeys had been subjected to 30% CR for 13-17 y relative to control-fed (CON) animals starting at 3-5 y of age.Same sex CR and CON monkeys exhibited similar levels of plaque, calculus, and bleeding on probing. Among CON animals, males showed significantly greater periodontal breakdown, as reflected by higher mean clinical attachment level and periodontal probing depth scores, than females. CR males exhibited significantly less periodontal pocketing, lower IgG antibody response, and lower IL-8 and ss-glucuronidase levels compared to CON males, whereas CR females showed a lower IgG antibody response but comparable clinical parameters and inflammatory marker levels relative to CON females. Long-term CR had no demonstrable effect on the periodontal microbiota.Males demonstrated greater risk for naturally occurring periodontal disease than females. Long-term CR may differentially reduce the production of local inflammatory mediators and risk for inflammatory periodontal disease among males but not females.

Aggregatibacter actinomycetemcomitans is frequently associated with localized aggressive periodontitis (LAP); however, longitudinal cohort studies relating A. actinomycetemcomitans to initiation of LAP have not been reported. A periodontal assessment was performed on 1,075 primarily African-American and Hispanic schoolchildren, ages 11 to 17 years. Samples were taken from each child for A. actinomycetemcomitans . A cohort of 96 students was established that included a test group of 38 A. actinomycetemcomitans -positive students (36 periodontally healthy and 2 with periodontal pockets) and 58 healthy A. actinomycetemcomitans -negative controls. All clinical and microbiological procedures were repeated at 6-month intervals. Bitewing radiographs were taken annually for definitive diagnosis of LAP. At the initial examination, clinical probing attachment measurements indicated that 1.2% of students had LAP, while 13.7% carried A. actinomycetemcomitans , including 16.7% of African-American and 11% of Hispanic students ( P = 0.001, chi-square test). A. actinomycetemcomitans serotypes a, b, and c were equally distributed among African-Americans; Hispanic students harbored predominantly serotype c ( P = 0.05, chi-square test). In the longitudinal phase, survival analysis was performed to determine whether A. actinomycetemcomitans -positive as compared to A. actinomycetemcomitans -negative students remained healthy (“survived”) or progressed to disease with attachment loss of >2 mm or bone loss (failed to “survive”). Students without A. actinomycetemcomitans at baseline had a significantly greater chance to remain healthy (survive) compared to the A. actinomycetemcomitans -positive test group ( P = 0.0001). Eight of 38 A. actinomycetemcomitans -positive and none of 58 A. actinomycetemcomitans -negative students showed bone loss ( P = 0.01). A. actinomycetemcomitans serotype did not appear to influence survival. These findings suggest that detection of A. actinomycetemcomitans in periodontally healthy children can serve as a risk marker for initiation of LAP.

Improved diagnostics remains a fundamental goal of biomedical research. This study was designed to assess cytokine biomarkers that could predict bone loss (BL) in localized aggressive periodontitis. 2,058 adolescents were screened. Two groups of 50 periodontally healthy adolescents were enrolled in the longitudinal study. One group had Aggregatibacter actinomycetemcomitans (Aa), the putative pathogen, while the matched cohort did not. Cytokine levels were assessed in saliva and gingival crevicular fluid (GCF). Participants were sampled, examined, and radiographed every 6 months for 2–3 years. Disease was defined as radiographic evidence of BL. Saliva and GCF was collected at each visit, frozen, and then tested retrospectively after detection of BL. Sixteen subjects with Aa developed BL. Saliva from Aa-positive and Aa-negative healthy subjects was compared to subjects who developed BL. GCF was collected from 16 subjects with BL and from another 38 subjects who remained healthy. GCF from BL sites in the 16 subjects was compared to healthy sites in these same subjects and to healthy sites in subjects who remained healthy. Results showed that cytokines in saliva associated with acute inflammation were elevated in subjects who developed BL (i.e., MIP-1α MIP-1β IL-α, IL-1β and IL-8; p

Recent data indicate that smoking is an important risk factor for the development of periodontitis. Smoking is also known to reduce serum immunoglobulin G (IgG) levels. Interestingly, patients with the localized form of early-onset periodontitis (LJP) have elevated levels of serum IgG2, and those who smoke are not clinically different from nonsmoking LJ subjects. In contrast, patients with the generalized form of early-onset periodontitis (G-EOP) who smoke have more extensive destruction than their nonsmoking counterparts. Given the effects of smoking on EOP and the association of IgG2 with less severe disease, we hypothesized that smoking might reduce serum IgG2 and that this might be most apparent in G-EOP. We therefore examined the effects of smoking on serum IgG subclass concentrations in race-matched groups: LJP, G-EOP, and age-matched periodontally healthy controls (NPs). Smoking status was established from serum cotinine levels, and serum IgG subclass concentrations were determined by using radial immunodiffusion. The data indicated that the effects of smoking were remarkably selective with respect to both IgG subclass and race. Smoking did not appear to have any effect on the concentration of IgG1 or IgG3 in either black or white subjects. In contrast, smoking was associated with depressed serum IgG2 concentrations in both white NP and G-EOP subgroups. Serum IgG2 levels in black subjects did not appear to be depressed by smoking, with the single striking exception of the black G-EOP subgroup which also had depressed serum IgG4 levels. The results here confirm that smoking has effects on serum immunoglobulin levels, but the effects were both race and serum IgG subclass specific. Furthermore, the periodontal diagnosis of EOP subjects appeared to be important, as indicated by the fact that IgG2 and IgG4 levels were reduced in smoking black G-EOP subjects whereas the IgG2 and IgG4 levels in black LJP and NP subjects were not reduced by smoking.

Localized juvenile periodontitis (LJP) runs in families, and a predisposition to develop disease appears to be inherited in an autosomal dominant fashion. Patients with LJP have elevated levels of serum immunoglobulin G2 (IgG2), and this is most striking in black LJP patients. We hypothesized that the markedly elevated serum IgG2 levels related to LJP status and race may be attributable to a fundamental difference in the response of black LJP leukocytes. To test this possibility, leukocytes from black LJP patients, black non-periodontitis (NP) controls, and white NP controls were cultured with a nonspecific mitogen (pokeweed mitogen) which stimulates immunoglobulin production. The levels of IgG2 produced were measured using an enzyme-linked immunosorbent assay. The results revealed that the serum IgG2 level differences among black LJP patients and white and black NP subjects were reproducible in peripheral blood leukocytes in vitro. Analysis revealed that B cells from the LJP patients appeared to be predisposed to produce high levels of IgG2. Further analysis supported the concept that the high IgG2 responses of B cells from black LJP patients were regulated by monocytes. Replacing the monocytes in cultures from white NP subjects with LJP monocytes from black patients resulted in production of IgG2 at levels that were comparable with those produced by the LJP B cells from black patients. In short, B cells from black LJP patients produce elevated levels of IgG2 in vitro, and at least part of this elevation appears to be attributable to regulation via the LJP monocytes.

Actinobacillus actinomycetemcomitans is frequently associated with severe periodontitis. Many periodontitis patients have elevated levels of serum IgG antibodies to A. actinomycetemcomitans, but the role of these antibodies is unknown. This study evaluated the functional capacity of anti-A. actinomycetemcomitans IgG antibody to enhance phagocytosis of A. actinomycetemcomitans by polymorphonuclear leukocytes. Chemoluminescence assays were done using sera from 64 subjects, 61 of whom had severe periodontitis; results were compared with the subject's anti-A. actinomycetemcomitans IgG titer and avidity. There was a strong correlation between chemoluminescence and antibody log titer (P < .00001) and a weak correlation between chemoluminescence and antibody avidity (P < .05). The results support the hypothesis that anti-A. actinomycetemcomitans IgG antibodies are important in promoting phagocytosis and killing of A. actinomycetemcomitans. Subjects who develop high levels of highly avid antibodies against A. actinomycetemcomitans may have greater resistance to continued or repeated infection by this pathogen.

Osteoclast development and growth were studied by determining the number of labelled nuclei in osteoclasts of different sizes (based on the number of nuclei per osteoclast, N/O) and the number of osteoclasts with labelled nuclei at various intervals after tritiated thymidine ([3H]TdR) injection in young rats. The osteoclast smears were made from the cellular periosteum of the proximal tibia. The frequency distribution of the N/O osteoclasts types in the smears had profiles similar to that of in situ osteoclasts in whole mounts of proximal tibia, which indicates that the osteoclast population of the smears was representative of that on the bone surface. A vast majority of the osteoclasts had a 1–6 N/O, and a number of the cells had as many as 26 or more nuclei. Furthermore, profiles of N/O frequency distributions were similar over the course of the study. Nuclei with [3H]TdR label were initially observed in osteoclasts between 4 and 12 hr after isotope injection. However, fusion of labelled nuclei to osteoclasts continued for at least 150 hr. In general, the labelled osteoclasts exhibited a significantly larger number of nuclei than the unlabelled osteoclasts. The probability of an osteoclast incorporating one or more labelled nuclei increased with time after injection and with an increase in N/O. Labelling intensity decreased with time post injection and with an increase in N/O. The data suggest that turnover of nuclei is more rapid in osteoclasts with high N/O values.

One hundred eight patients with a histologically confirmed diagnosis of epithelial dysplasia of the oral cavity and a prior history of smokeless tobacco (ST) usage were identified. The mean age at time of diagnosis for female patients was almost a decade later than for male patients (63.6 versus 51.2 years). In addition, women were more likely (P = 0.02) to have moderate or severe epithelial dysplasia than men. The two most common locations (buccal mucosa/vestibule and alveolar ridge/gingiva) accounted for 82.4% of all cases. In the 44 cases which specified both ST placement and biopsy site, 90.9% demonstrated epithelial dysplasia at the location used by the patient for holding the ST. When evaluating the histologic severity of epithelial dysplasia, a trend (P = 0.02) toward focal mild or mild was noted among ST users as compared to nonusers. No difference was found in the histologic grade of the lesions associated with either snuff or chewing tobacco.