Bruce L. Pihlstrom

A Twin Study of Genetic Variation in Proportional Radiographic Alveolar Bone Height

The purpose of this study was to estimate the genetic variance for alveolar bone height by means of the classic twin method and the study of monozygous twins reared apart. Panoramic radiographs were obtained from 120 pairs of adult twins (mean age = 40.4 years, S.D. = 10.4 years), for comparison of 62 pairs of monozygous twins reared together (MZT), 25 pairs of like-sexed dizygous twins reared together (DZT), and 33 pairs of monozygous twins reared apart (MZA). Mesial and distal bone heights were determined as a proportion of tooth length. A full-mouth bone score was computed for each twin by averaging these proportions from all measurable teeth. Between-pair (B) and within-pair (W) variances were computed for each twin group. The population variances (B + W) of the MZT and DZT twin groups were similar, which validated a basic assumption of the twin model. Intraclass correlations and heritability estimates were also computed for the reared-together and reared-apart twin groups. Boot-strap sampling was used to provide estimates and confidence limits for these values. The intraclass correlations for the twin groups were: MZT = 0.70, DZT = 0.52, and MZA = 0.55. The results of this study suggest that there is significant genetic variance in the population for proportional alveolar bone height.

A critical assessment of adverse pregnancy outcome and periodontal disease

BACKGROUND Pre-term birth is a major cause of infant mortality and morbidity that has considerable societal, medical, and economic costs. The rate of pre-term birth appears to be increasing world-wide and efforts to prevent or reduce its prevalence have been largely unsuccessful. AIM To review the literature for studies investigating periodontal disease as a possible risk factor for pre-term birth and adverse pregnancy outcomes. MAIN FINDINGS AND CONCLUSION Variability among studies in definitions of periodontal disease and adverse pregnancy outcomes as well as widespread inadequate control for confounding factors and possible effect modification make it difficult to base meaningful conclusions on published data. However, while there are indications of an association between periodontal disease and increased risk of adverse pregnancy outcome in some populations, there is no conclusive evidence that treating periodontal disease improves birth outcome. Based on a critical qualitative review, available evidence from clinical trials indicates that, although non-surgical mechanical periodontal treatment in the second trimester of pregnancy is safe and effective in reducing signs of maternal periodontal disease, it does not reduce the rate of pre-term birth. Clinical trials currently underway will further clarify the potential role of periodontal therapy in preventing adverse birth outcomes. Regardless of the outcomes of these trials, it is recommended that large, prospective cohort studies be conducted to assess risk for adverse pregnancy outcome in populations with periodontal disease. It is critical that periodontal exposure and adverse birth outcomes be clearly defined and the many potential confounding factors and possible effect modifiers for adverse pregnancy outcome be controlled in these studies. If periodontal disease is associated with higher risk of adverse pregnancy outcome in these specific populations, large multicenter randomized-controlled trials will be needed to determine if prevention or treatment of periodontal disease, perhaps combined with other interventions, has an effect on adverse pregnancy outcome in these women.

MEASUREMENT OF ATTACHMENT LEVEL IN CLINICAL TRIALS : PROBING METHODS

Measurement of clinical attachment level has become a standard for judging clinical response in periodontal therapy. A number of probing methods and instruments have been developed in an attempt to address limitations in obtaining this measurement. First generation instruments include conventional periodontal probes; second generation probes utilize controlled forces; and third generation probes incorporate automated measurement, controlled forces, and computerized data capture. Various types of Stents have been used and repeated measurement techniques have been proposed to reduce examiner error. Controlled force probes appear to have their greatest advantage in increasing inter-examiner repeatability. The use of measurement Stents increases inter- and intra-examiner reliability. However, use of such Stents may be limited to small sample studies of limited duration. Third generation instruments offer advantages in terms of automated measurement and data capture, increased resolution, and a more continuous measurement scale, but do not necessarily result in increased intra-or inter-examiner reliability. Examiner training and calibration are essential for any measurement instrument. Decisions for or against use of a particular instrument must be made on the basis of the needs of each clinical trial. At the present time, no commercially available instrument resolves all of the inherent limitations of clinical measurement of attachment level. J Periodontol 1992; 63:1072-1077.

No Heritability of Temporomandibular Joint Signs and Symptoms

The causes of temporomandibular joint (TMJ)-rclatcd signs and symptoms are largely unknown. We tested the hypotheses that these signs and symptoms, as well as oral parafunctional habits, are substantially heritable. Questionnaire and clinical data were collected from 494 twins, including pairs of reared-apart and reared-together monozygotic (MZ) and dizygotic (DZ) twins. A history of joint-area pain, joint noises, and clenching and grinding habits was scorcd as present or absent. Twenty-nine percent of the population experienced at least one sign or symptom. Nearly one-quarter of subjects clenched or ground their teeth, and 8.7% reported a history of joint-area pain. Pain was associated with clenching, grinding, and joint noises. MZ twins were no more similar than DZ twins for any outcome, suggesting that genetic factors do not influence these traits in the population. Reared-together MZ twins were no more similar than reared-apart MZ twins, suggesting a negligible effect of the family environment on these outcomes. Environmental factors unique to each twin appeared to be the major determinants of variation in this population.

Design, Operation, and Interpretation of Clinical Trials

Randomized controlled clinical trials offer the best evidence for changing clinical practice and informing public health policy. Using examples from the literature, this paper reviews clinical trials for those who may be unfamiliar with their design, operation, and interpretation. In the design of a clinical trial, the question to be answered and a clinically meaningful outcome must be clearly defined. Ethics must be considered, sample size carefully estimated, and use of biomarkers and surrogate outcomes understood. Prominent issues in trial implementation include developing a manual of operations, trial registration, subject recruitment and retention, use of a data coordinating center, and data and safety monitoring. Interpretation of clinical trials requires understanding differences between efficacy and effectiveness; superiority, equivalence, and non-inferiority; intent-to-treat; primary and secondary analyses; and limitations of unregistered small clinical trials compared with large multi-center Phase III trials that are more likely to be representative of a population and change clinical practice or public health policy.

Multiple-outcomes Meta-analysis of Treatments for Periodontal Disease

The results of periodontal therapy vary by disease severity, outcome measure, and method of data analysis. Several clinical trials and a subsequent meta-analysis have demonstrated that, for teeth with severe disease, surgery decreases probing depth (PD) and increases attachment level (AL) more than non-surgical treatment. For other disease levels, the choice of therapy depends on the outcome measure. When clinical trials use two or more outcome measures (such as PD and AL), investigators ordinarily analyze each outcome separately. When the correlations are incorporated among the outcomes, a meta-analysis can use generalized-least-squares (GLS) regression to analyze multiple outcomes jointly. We applied the GLS multiple-outcomes model in a meta-analysis of 5 trials comparing surgical and non-surgical periodontal treatments, each assessing the outcomes PD and AL one year after treatment. The clinical conclusions are similar to those reported earlier, but our estimates of the relative benefits of surgical and non-surgical treatment should be more accurate, because the GLS method takes into account correlation between AL and PD. When correlations between the two outcomes rise, as they do with increasing severity of disease, the GLS estimates depart from those derived from separate analyses of PD and AL.

Randomized controlled trials: what are they and who needs them?

Dentistry is rapidly entering a new era of evidence-based practice, and society is demanding prevention and treatment that has been proven to be effective in terms of meaningful health outcomes. Practitioners, individual patients and the public need randomized controlled trials because they provide the highest level of scientific evidence to change clinical practice and inform public health policy. Well-designed randomized controlled trials are conceptually simple but deceptively complex to design, implement and translate into clinical practice. Randomized controlled trials are fundamentally different from observational clinical research because they randomly assign volunteers to receive test or control interventions, they are prospective and the success of the test intervention is based on a meaningful clinical outcome that is specified before the trial begins. To be successful, randomized controlled trials must be carefully designed and powered to answer a specific question that will be generalizable to the population under study. Randomized controlled trials can be designed to evaluate efficacy, effectiveness, superiority, equivalence or noninferiority. Prominent issues and challenges in designing and conducting randomized controlled trials include carefully defining enrollment criteria, establishing an organizational infrastructure, use of a data-coordinating center, developing a manual of procedures, obtaining informed consent, recruiting and ensuring the safety of volunteer subjects, ensuring data quality, analysis and publication of trial outcomes, and translating results into clinical practice.

Histopathology and electron and immunofluorescence microscopy of gingivitis granulomatosa associated with glossitis and cheilitis in a case of Anderson-Fabry disease

A 17-year-old white boy with signs, symptoms, and family history of angiokeratoma corporis diffusum universale, Anderson-Fabry disease (AFD), developed recurrent and then persistent swelling of both lips, erythematous hyperplastic gingivae, and a pebbled tongue. Positive blood findings were raised serum IgE, decreased T-cell level, and increased B-cell level. Histopathology of the gingiva showed noncaseating granulomas with multinucleate giant cells containing Schaumann bodies and large plasma-cell infiltrates in which immunofluorescence demonstrated immune globulins of several classes. Electron microscopy and histochemistry demonstrated ceramide in the vasculature. No glycolipid was found in the macrophages or giant cells of the granulomas which, in contrast, resembled sarcoid reactions. Plasma cells with Russell bodies and immune reaction-induced degranulation of mast cells were also identified. The pathogenesis of the oral findings possibly relates to altered immune reactivity associated with damage to the microvasculature analogous to that in Melkersson-Rosenthal syndrome.

Effect of gingival fluid collection on subgingival plaque sampling

The purpose of this study was to determine whether gingival crevicular fluid (GCF) sampling by paper strip removes sufficient bacteria to affect subsequent subgingival plaque sampling using a curette. In 25 subjects, one healthy, gingivitis and periodontitis site was sampled for GCF using a strip followed by subgingival plaque sampling with a curette. Bacterial assays indicated that GCF strips removed significant numbers of bacteria when placed intracrevicularly for 5 s. A greater proportion of total bacteria was removed with strip sampling at healthy rather than gingivitis or periodontitis sites. Qualitative assessment of presence or absence of spirochaetes and dark-pigmented species indicated potential for significant interference of curette sampling by the strip at gingivitis and healthy sites. We concluded that paper strip GCF sampling may significantly affect curette sampling at the same sites. The magnitude of this impact depended on the clinical classification of specific sites and the assay performed.

Diabetes and periodontal therapy.

This issue of The Journal of the American Dental Association (JADA) contains a report1 of the periodontal treatment response among people who participated in the Diabetes and Periodontal Therapy Trial (DPTT).2 The DPTT is a large, multicenter randomized controlled clinical trial that was designed to study the effect of nonsurgical periodontal therapy among people who have type 2 diabetes mellitus and periodontitis. The periodontal treatment consisted of two or more sessions of scaling and root planing (totaling more than 2.5 hours and involving the use of local anesthetic) and follow-up supportive periodontal care. The main conclusion of this six-month trial was that nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes who had periodontitis.2 This trial has received considerable attention because its findings are contrary to what many people anticipated—and because it did not support results of smaller clinical trials and meta-analyses that showed improvements in hemoglobin A1c (HbA1c) levels as a result of nonsurgical periodontal therapy.3 We wish to address the generalizability of the DPTT. As reported by the authors in this issue of JADA,1 the patient sample of the DPTT reflects the population of people with diabetes in the United States. The DPTT included participants who had type 2 diabetes with HbA1c levels between 7 percent and less than 9 percent; 72 percent of the participants were obese (body mass index [BMI] greater than 30 kilograms per square meter).1 The National Health and Nutrition Examination Survey is a population-based survey of people with diabetes in the United States; its results demonstrated that only 12.6 percent of people with diabetes in the United States are estimated to have HbA1c levels greater than 9 percent and 62.4 percent to have a BMI of 30 or greater.4,5 The DPTT does not address the possible effect of periodontal treatment in the 12 percent of the population with HbA1c levels greater than 9 percent or the 50 percent of the population with HbA1c levels less than 7 percent, because efforts were made to exclude these patients. However, the magnitude of obesity was not constrained by trial entry criteria. Patients with type 2 diabetes who have HbA1c levels higher than 9 percent and a BMI of less than 30 are rare. Because the participant sample was typical of patients with diabetes both in terms of HbA1c and obesity, the results of the DPTT should be viewed as fully generalizable to patients with diabetes in the United States.