A quantitative bias analysis to assess the impact of unmeasured confounding on associations between diabetes and periodontitis.

AIM: To investigate unmeasured confounding in bidirectional associations between periodontitis and diabetes using quantitative bias analysis. METHODS: Subsamples from the Veterans Affairs Dental Longitudinal Study were selected. Adjusted for known confounders, we used Cox proportional hazards models to estimate associations between pre-existing clinical periodontitis and incident Type II Diabetes (n = 672), and between pre-existing diabetes and incident severe periodontitis (n = 521), respectively. Hypothetical confounders were simulated into the dataset using Bernoulli trials based on pre-specified distributions of confounders within categories of each exposure and outcome. We calculated corrected hazard ratios (HR) over 10,000 bootstrapped samples. RESULTS: In models using periodontitis as the exposure and incident diabetes as the outcome, adjusted HR = 1.21 (95% CI: 0.64-2.30). Further adjustment for simulated confounders positively associated with periodontitis and diabetes greatly attenuated the association or explained it away entirely (HR = 1). In models using diabetes as the exposure and incident periodontitis as the outcome, adjusted HR = 1.35 (95% CI: 0.79-2.32). After further adjustment for simulated confounders, the lower bound of the simulation interval never reached the null value (HR ≥ 1.03). CONCLUSIONS: Presence of unmeasured confounding does not explain observed associations between pre-existing diabetes and incident periodontitis. However, presence of weak unmeasured confounding eliminated observed associations between pre-existing periodontitis and incident diabetes. These results clarify the bidirectional periodontitis-diabetes association.

The impact of periodontitis exposure misclassification bias from partial-mouth measurements on association with diabetes and cardiovascular disease.

AIM: To quantify exposure misclassification bias arising from use of partial-mouth protocols in studies of periodontitis-systemic disease associations. MATERIALS AND METHODS: Using data from 10,134 adults participating in the National Health and Nutrition Examination Survey, we classified periodontal status based on full-mouth clinical examinations and three commonly used partial-mouth protocols. Associations between periodontitis and self-reported diabetes and cardiovascular disease were evaluated under each protocol using adjusted logistic regression. Percent relative bias was calculated to evaluate magnitude and direction of bias. RESULTS: Misclassification primarily resulted in underestimation of associations, the extent of which depended on both the outcome under study and exposure severity. Bias due to misclassification of severe periodontitis was negligible for cardiovascular disease (0%-4.1%) compared to diabetes (177.7%-234.1%). In contrast, bias in moderate periodontitis associations was comparable across each outcome-diabetes (28.4%-39.5%) and cardiovascular disease (8.9%-46.7%). Results did not meaningfully change based on the partial-mouth protocol implemented. Stratified analyses showed increased bias among those with ≤15 teeth. Use of mean attachment loss as a continuous exposure resulted in minimal-to-no bias. CONCLUSIONS: Exposure misclassification bias due to use of partial-mouth protocols can yield inaccurate conclusions about periodontitis-systemic disease associations, the extent of which may depend on periodontitis classification and the association under study.

Improving Diversity of Dental Students Through the Boston University Master's of Oral Health Sciences Postbaccalaureate Program.

Boston University Goldman School of Dental Medicine (GSDM), in collaboration with Boston University School of Medicine, introduced the Oral Health Sciences (OHS) pipeline program in 2005 to enhance the academic preparedness of students from underrepresented minority (URM) groups for dental school admission. The aim of this study was to evaluate the OHS program's success in preparing URM students for dental school, as measured by acceptance to dental school and performance in the first and second years. Data on 2005-15 program enrollees were collected from admissions records, the registrar, and the Office of Institutional Research on students' race/ethnicity, undergraduate and OHS grade point average (GPA), and Dental Admission Test (DAT) scores. Acceptance to dental school and performance at GSDM for non-URM OHS graduates, URM OHS graduates, and non-OHS dental students were compared. A total of 55 URM students completed the OHS program during this period, with 49 successfully matriculating to a dental school in the U.S. and 33 attending GSDM. Average OHS GPA was higher for those URM students accepted to dental school than for those who did not gain admission (3.36±0.30 vs. 2.94±0.19). Evaluation of the academic performance of URM OHS students in the first year (p=0.13) and second year (p=0.88) at GSDM showed that these students performed as well as the non-OHS and non-URM OHS students. These results demonstrate that the OHS master's program serves as a successful credential-enhancing program for dental school applicants, while also serving as a pipeline to increase the number of qualified applicants from URM groups.

Dental Educators' Perceptions of Educational Learning Domains.

The aim of this study was to seek the views of a national sample of dental educators regarding the importance of learning domains in dental education, their defined outcomes of those domains, and their perceived effectiveness of their schools in guiding learning in those domains. The study defined the educational domains important for training future dentists as knowledge, technical skills, critical thinking, ethics, social responsibility, and interprofessional education/practice (IPE/IPP). A survey of members of the American Dental Education Association (ADEA) Special Interest Group on the Scholarship of Teaching and Learning was conducted in 2017. In addition to reporting their demographics, participants were asked to rate and rank the importance of each learning domain as well as answer open-ended questions. Of the 89 respondents (response rate 12.5%), 31% were course directors, and 48% had been dental faculty members for more than ten years. Knowledge was ranked as the most important domain, followed by critical thinking, technical skills, clinical decision making, ethics, problem-solving, social responsibility, and finally IPE/IPP. When rating the absolute importance of these domains in the training of dental students, the respondents gave all but IPE/IPP and social responsibility the highest rating. Knowledge and technical skills were rated highest for respondents' confidence in defining student outcomes with similar high ratings for their confidence in guiding this learning. There was little consensus concerning a definition of critical thinking, and a third of the respondents were uncertain of specific learning outcomes for it. Participants expressed even less confidence in defining outcomes for ethics, IPE/IPP, and social responsibility. This baseline information will be used for a future in-depth study to aid in the development of strategies for articulating outcomes, guiding learning, and assessing performance in U.S. dental schools.

Incisor malalignment and the risk of periodontal disease progression.

INTRODUCTION: The objective of this study was to investigate the association between incisor crowding, irregularity, and periodontal disease progression in the anterior teeth. METHODS: Data collected over 35 years from men enrolled in the Veterans Affairs Dental Longitudinal Study included information concerning pocket depth and alveolar bone loss. Plaster casts of the maxillary (n = 400) and mandibular (n = 408) arches were available for baseline measurements. Periodontal disease in the anterior teeth was defined as per arch sum of pathologic pocket depth and sum of teeth with any alveolar bone loss in the anterior sextants. Incisor malalignment status was defined by the anterior tooth size-arch length discrepancy index and Little's Irregularity Index. Adjusted mixed effects linear models computed the beta (ß) estimates and 95% confidence intervals (95% CI) of the amounts of change in periodontal disease outcomes by the level of malalignment. RESULTS: In the anterior maxillary arch, crowding and spacing were significantly associated with an increased per-arch sum of pathologic pocket depth (ß, 0.70 mm; 95% CI, 0.20-1.21, and ß, 0.49 mm; 95% CI, 0.06-0.91, respectively). In the anterior mandibular arch, incisor crowding and irregularity were significantly associated with an increased per-arch sum of pathologic pocket depth (mild crowding: ß, 0.47 mm; 95% CI, 0.01-0.93; severe irregularity: ß, 0.94 mm; 95% CI, 0.50-1.38), and the sum number of teeth with alveolar bone loss (mild and moderate-to-severe crowding: ß, 0.45 teeth; 95% CI, 0.08-0.82; and ß, 0.45 teeth; 95% CI, 0.13-0.83, respectively; moderate irregularity: ß, 0.34 teeth; 95% CI, 0.06-0.62). CONCLUSIONS: Certain incisor malalignment traits (ie, maxillary incisor crowding, maxillary incisor spacing, mandibular incisor mild crowding, mandibular incisor moderate-to-severe crowding, mandibular incisor moderate irregularity, and mandibular incisor severe irregularity) are associated with significant periodontal disease progression.

Local intraoral autologous bone harvesting for dental implant treatment: alternative sources and criteria of choice.

Dental implants are established alternatives for replacing missing teeth. In case of alveolar bone resorption, implant placement may be prevented unless the volume of hard tissues is increased before or during implantation. Autologous bone graft is still regarded as the "gold standard" in alveolar reconstruction., but many factors may influence the final outcome. The success of intraoral bone grafts, in fact, depends, among other factors, on the choice of donor graft material as well as on how the material is handled. The evidence supporting the use of autogenous intramembranous bone with or without the use of barrier membranes is briefly reviewed. The rational of donor site choice is also presented. Advantages and disadvantages of different harvesting site are discussed.

Diminished bone formation during diabetic fracture healing is related to the premature resorption of cartilage associated with increased osteoclast activity.

UNLABELLED: Histological and molecular analysis of fracture healing in normal and diabetic animals showed significantly enhanced removal of cartilage in diabetic animals. Increased cartilage turnover was associated with elevated osteoclast numbers, a higher expression of genes that promote osteoclastogenesis, and diminished primary bone formation. INTRODUCTION: Diminished bone formation, an increased incidence of nonunions, and delayed fracture healing have been observed in animal models and in patients with diabetes. Fracture healing is characterized by the formation of a stabilizing callus in which cartilage is formed and then resorbed and replaced by bone. To gain insight into how diabetes affects fracture healing, studies were carried out focusing on the impact of diabetes on the transition from cartilage to bone. MATERIALS AND METHODS: A low-dose treatment protocol of streptozotocin in CD-1 mice was used to induce a type 1 diabetic condition. After mice were hyperglycemic for 3 weeks, controlled closed simple transverse fractures of the tibia were induced and fixed by intramedullary pins. Histomorphometric analysis of the tibias obtained 12, 16, and 22 days after fracture was performed across the fracture callus at 0.5 mm proximal and distal increments using computer-assisted image analysis. Another group of 16-day samples were examined by microCT. RNA was isolated from a separate set of animals, and the expression of genes that reflect the formation and removal of cartilage and bone was measured by real-time PCR. RESULTS: Molecular analysis of collagen types II and X mRNA expression showed that cartilage formation was the same during the initial period of callus formation. Histomorphometric analysis of day 12 fracture calluses showed that callus size and cartilage area were also similar in normoglycemic and diabetic mice. In contrast, on day 16, callus size, cartilage tissue, and new bone area were 2.0-, 4.4-, and 1.5-fold larger, respectively, in the normoglycemic compared with the diabetic group (p < 0.05). Analysis of microCT images indicated that the bone volume in the normoglycemic animals was 38% larger than in diabetic animals. There were 78% more osteoclasts in the diabetic group compared with the normoglycemic group (p < 0.05) on day 16, consistent with the reduction in cartilage. Real-time PCR showed significantly elevated levels of mRNA expression for TNF-alpha, macrophage-colony stimulating factor, RANKL, and vascular endothelial growth factor-A in the diabetic group. Similarly, the mRNA encoding ADAMTS 4 and 5, major aggrecanases that degrade cartilage, was also elevated in diabetic animals. CONCLUSIONS: These results suggest that impaired fracture healing in diabetes is characterized by increased rates of cartilage resorption. This premature loss of cartilage leads to a reduction in callus size and contributes to decreased bone formation and mechanical strength frequently reported in diabetic fracture healing.

Immunization enhances inflammation and tissue destruction in response to Porphyromonas gingivalis.

It is well established that host-bacterium interactions play a critical role in the initiation and progression of periodontal diseases. By the use of inhibitors, it has been shown that mediators associated with the innate immune response significantly contribute to the disease process. Less is known regarding the role of the acquired immune response. To investigate mechanisms by which the acquired immune response to Porphyromonas gingivalis could affect connective tissue, we used a well-documented calvarial model to study host-bacterium interactions. Injection of P. gingivalis stimulated gamma interferon, interleukin 6, macrophage inflammatory protein 2, and monocyte chemoattractant protein 1 expression as determined by real-time PCR. Prior immunization against P. gingivalis significantly enhanced the mRNA levels of these cytokines and chemokines. Similarly, immunization significantly increased and prolonged the formation of a polymorphonuclear leukocyte and mononuclear cell infiltrate (P < 0.05). In addition, the area of connective tissue destruction, osteoclastogenesis, bone loss, mRNA expression of proapoptotic genes, and degree of fibroblast apoptosis were increased in immunized mice (P < 0.05). These results indicate that activation of the acquired immunity by P. gingivalis increases the inflammatory and destructive responses which occur in part through up-regulating the innate immune response and enhancing osteoclastogenesis and fibroblast apoptosis.

Morphometric analysis of the furcation anatomy of mandibular molars.

BACKGROUND: Successful treatment of molar furcation defects remains a challenge in clinical practice. Knowledge of anatomic factors facilitates predictable management of furcation involvement lesions. The degree of success in managing furcation involvement is inversely related to the horizontal probing depth. The depth of the horizontal component of attachment loss can vary depending on the external tooth-surface reference points used. However, the anatomical factors affecting horizontal component of attachment loss have not been previously assessed. Therefore, this study determined the bucco-lingual measurements of the cemento-enamel junction and the mesial and distal roots and at the level of root separation. METHODS: One hundred extracted permanent human mandibular first (N = 50) and second (N = 50) molars were studied. Four horizontal bucco-lingual widths were measured with calibrated calipers: 1) furcation entrance/roof (FE); 2) cemento-enamel junction level (CEJ); 3) mesial root width (MRW); and 4) distal root width (DRW). RESULTS: The mean widths at FE, CEJ, MRW, and DRW were, respectively, 5.53 +/- 0.45 mm, 8.71 +/- 0.54 mm, 8.57 +/- 0.54 mm, and 7.97 +/- 0.65 mm in the first molars and 5.61 +/- 0.65 mm, 8.40 +/- 0.65 mm, 7.95 +/- 0.88 mm, and 7.16 +/- 0.84 mm in the second molars. Analysis of variance revealed significant differences between FE and the other variables tested. The results showed that the bucco-lingual width of the furcation roof is considerably shorter than the MRW and DRW. The difference in the mean bucco-lingual dimension between FE and the other measurements occurred in all teeth evaluated and varied between 0.7 and 4.30 mm. CONCLUSIONS: Our findings demonstrate that clinical measurements of horizontal probing depth that use the external surfaces of roots as reference points overestimate the true anatomical component of furcation involvement in mandibular molars. Conversely, positive treatment outcomes in these teeth may be underestimated. This has implications not only for clinical practice but also for clinical research studies evaluating treatment outcomes.

Human salivary gland-specific daily variations in histatin concentrations determined by a novel quantitation technique.

Histatins constitute a distinct family of human salivary antimicrobial peptides, of which histatins 1, 3 and 5 are the most abundant. To evaluate salivary gland-specific differences in histatin secretion, we used the recently developed histatin-zinc precipitation method to quantify histatins and to assess daily variations in secretions. Stimulated pure secretions from parotid glands (HPS) and submandibular/sublingual glands (SMSL) were collected from 10 different subjects at four different times of the day (9:35 a.m.; 12:40 p.m.; 2:50 p.m. and 5:00 p.m.). Zinc precipitation and subsequent reversed phase HPLC analysis were performed to determine concentrations of histatins 1, 3 and 5 with reference to purified histatin standards. Both HPS and SMSL secretions displayed daily variations in histatin concentrations. HPS values showed a maximum at mid-day and SMSL samples showed a maximum in the morning. Mean daily histatin concentrations were almost three fold higher in SMSL than in HPS. Mean histatin 1, 3 and 5 concentrations in HPS from 10 subjects ranged from 0.7 to 2.8, 0.6 to 4.3 and 1.0 to 4.3mg%, respectively. The corresponding means in SMSL were 2.8-12.2, 1.5-7.5 and 2.6-9.0mg%, respectively. Remarkably, although histatins constitute only 3-10% of total protein in these secretions, an almost perfect correlation between total protein and total histatin concentrations was observed for both glands. Despite a broad range in histatin concentrations between individuals, this study demonstrated a hitherto unidentified daily variation in histatin concentrations in HPS and SMSL secretions and a differential expression pattern which might have functional implications.

Diabetes causes decreased osteoclastogenesis, reduced bone formation, and enhanced apoptosis of osteoblastic cells in bacteria stimulated bone loss.

The most common cause of inflammatory bone loss is periodontal disease. After bacterial insult, inflammation induces bone resorption, which is followed by new reparative bone formation. Because diabetics have a higher incidence and more severe periodontitis, we examined mechanisms by which diabetes alters the response of bone to bacterial challenge. This was accomplished with db/db mice, which naturally develop type 2 diabetes. After inoculation of bacteria osteoclastogenesis and bone resorption was measured. Both parameters were decreased in the diabetic group. Diabetes also suppressed reparative bone formation measured histologically and by the expression of osteocalcin. The impact of diabetes on new bone formation coincided with the effect of diabetes on apoptosis of bone-lining cells. Within 5 d of bacterial challenge, apoptosis declined in the wild-type animals yet remained significantly higher in the diabetic group. Thus, diabetes may cause a net loss of bone because the suppression of bone formation is greater than the suppression of bone resorption. The uncoupling of bone formation and resorption may be due in part to prolonged apoptosis of bone lining cells.