Free sugars and gingival inflammation: A systematic review and meta-analysis.

AIM: Consumption of free sugars has been associated with chronic non-communicable diseases. The aim of the study was to investigate the effect of free-sugar consumption on gingival inflammation using a systematic review and meta-analysis based on the PICO question 'What impact does the restriction of free sugars have on the inflammation of gingival tissue?' MATERIALS AND METHODS: Literature review and analyses were based on the Cochrane Handbook for Systematic Reviews of Interventions. Controlled clinical studies reporting on free-sugar interventions and gingival inflammation were included. Risk of bias was performed with ROBINS-I and ROB-2, and effect sizes were estimated with robust variance meta-regressions. RESULTS: Of the 1777 primarily identified studies, 1768 were excluded, and 9 studies with 209 participants with gingival inflammation measures were included. Six of these studies reported on the dental plaque scores of 113 participants. Restriction of free sugars, when compared with no such restriction, was associated with statistically significantly improved gingival health scores (standard mean difference [SMD] = -0.92; 95% confidence interval [CI]: -1.43 to -0.42, p < .004; I2 [heterogeneity] = 46.8) and a trend towards lower dental plaque scores (SMD = -0.61; 95% CI: -1.28 to 0.05, p < .07; I2 = 41.3). The observed improvement of gingival inflammation scores with restricted consumption of free sugar was robust against various statistical imputations. No meta-regression models were feasible because of the limited number of studies. The median publication year was 1982. Risk-of-bias analysis showed a moderate risk in all studies. CONCLUSION: Restriction of free sugar was shown to be associated with reduced gingival inflammation. The systematic review was registered at PROSPERO (CRD 42020157914).

Dental risk factors for osteonecrosis of the jaws: a CONDOR case-control study.

BACKGROUND: Reports of osteonecrosis of the jaw (ONJ) have associated this lesion to treatment with bisphosphonates (BPs) and dental procedures. In this study, we investigated the association of specific dental diagnoses and procedures with ONJ among patients with past BP use. METHODS: Dentists from three practice-based research networks provided ONJ cases and controls (1:3). Data gathered from patients and dental offices with two respective standard questionnaires included demographic, medical, pharmaceutical, and dental information. Diagnoses and procedures up to 3 years prior to ONJ (prior to interview for controls) were analyzed within risk strata, defined by BP use and cancer status, using interaction terms within conditional logistic regression models. RESULTS: We enrolled 191 ONJ cases and 573 controls from 119 dental offices. Among participants who had used only oral BP, extraction was the only dental risk factor for ONJ (odds ratio (OR) = 12, p = 0.01). Suppuration was also more prevalent in cases (18 %) than in controls (9 %), but not statistically significant (OR = 9, p = 0.06). Among participants who had not used either oral or IV BP (a majority of whom received radiation therapy to the head and neck), suppuration was the only dental risk factor for ONJ (prevalence = 34 % for cases and 8 % for controls; OR = 7, p = 0.01). The prevalence of extractions in this group was also higher, but not statistically significant (44 vs 10 %; OR = 3). Limited power precludes definitive findings among participants exposed to IV BP. CONCLUSIONS: Among patients taking oral BP, extraction was the only dental procedure associated with subsequent ONJ development CLINICAL RELEVANCE: Results of this study suggest that routine dental procedures are not associated with development of ONJ in patients exposed to BPs.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR Dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with 3 dental practice-based research networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95% CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased 4-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment >2 years; suppuration and dental extractions were independent risk factors for ONJ.

Systemic antibiotics and tooth loss in periodontal disease.

Systemic antibiotics have been recommended for the treatment of destructive periodontal disease. Our goal was to relate antibiotic use for medical or dental reasons to subsequent tooth loss in a cohort of 12,631 persons with destructive periodontal disease. After adjustment for age, smoking, and other confounders, the dispensing of antibiotics for 1-13 days, 14-20 days, or 21 or more days was not associated with reduced tooth loss [Adjusted rate ratio (RR) = 1.0; 95% Confidence Interval (CI) = 0.8-1.1; RR = 1.2; 95% CI = 0.9-1.4, and RR =1.2, 95% CI =1.0-1.3, respectively]. Numerous subgroup analyses were consistent with these overall null findings, with two exceptions: Longer courses of tetracyclines were associated with reduced tooth loss among persons receiving periodontal care, and penicillin was associated with reduced tooth loss among persons with more severe disease. Long-term, larger randomized trials are needed to provide evidence that antibiotics reduce tooth loss when used in the management of destructive periodontal disease.

Secular trends in socio-economic disparities in edentulism: USA, 1972-2001.

For health care planning and policy, it is important to determine whether socio-economic disparities in edentulism, an ultimate marker of oral health, have improved over time. The aim of this study was to investigate the socio-economic disparities in edentulism between 1972 and 2001. Representative samples of the United States population, 25-74 years old, were obtained from NHANES I (1972), III (1991), and 1999-2002. Differences in the edentulism prevalence between high and low socio-economic positions (SEP) were compared. Differences in edentulism prevalence remained stable over approximately three decades (p = 0.480), being 10.6 percentage points in 1972, 12.1 percentage points in 1991, and 11.3 percentage points in 2001. Exploratory subgroup analyses suggested that disparities decreased for those individuals reporting a dental visit in the prior year and those reporting never having smoked. In conclusion, the absolute prevalence difference in edentulism between low and high socio-economic positions has remained unchanged over the last three decades.

Chlorhexidine and preservation of sound tooth structure in older adults. A placebo-controlled trial.

The Trial to Enhance Elderly Teeth Health (TEETH) was designed to test the impact of regular rinsing with a 0.12% chlorhexidine (CHX) solution on tooth loss, and the causes of tooth loss (caries, periodontal disease and trauma) were also investigated. This paper reports on the effectiveness of a 0.12% CHX solution for controlling caries using a tooth surface (coronal and root) survival analysis. A total of 1,101 low income elders in Seattle (United States) and Vancouver (Canada), aged 60-75 years, were recruited for a double-blind clinical trial and assigned to either a CHX (n = 550) or a placebo (n = 551) mouth rinse. Subjects alternated between daily rinsing for 1 month, followed by weekly rinsing for 5 months. All sound coronal and root surfaces at baseline were followed annually for up to 5 years. At each follow-up examination, those tooth surfaces with caries, restored, or extracted were scored as 'carious'. The hazard ratio associated with CHX for a sound surface to become filled, decayed, or extracted was 0.87 for coronal surfaces (95% confidence interval: 0.71-1.14, p = 0.20) and 0.91 for root surfaces (95% confidence interval: 0.73-1.14, p = 0.41). These findings suggest that regular rinsing with CHX does not have a substantial effect on the preservation of sound tooth structure in older adults.

Dental flossing and interproximal caries: a systematic review.

Our aim was to assess, systematically, the effect of flossing on interproximal caries risk. Six trials involving 808 subjects, ages 4 to 13 years, were identified. There were significant study-to-study differences and a moderate to large potential for bias. Professional flossing performed on school days for 1.7 years on predominantly primary teeth in children was associated with a 40% caries risk reduction (relative risk, 0.60; 95% confidence interval, 0.48-0.76; p-value, < 0.001). Both three-monthly professional flossing for 3 years (relative risk, 0.93; 95% confidence interval, 0.73-1.19; p-value, 0.32) and self-performed flossing in young adolescents for 2 years (relative risk, 1.01; 95% confidence interval, 0.85-1.20; p-value, 0.93) did not reduce caries risk. No flossing trials in adults or under unsupervised conditions could be identified. Professional flossing in children with low fluoride exposures is highly effective in reducing interproximal caries risk. These findings should be extrapolated to more typical floss-users with care, since self-flossing has failed to show an effect.

Statin use and tooth loss in chronic periodontitis patients.

BACKGROUND: Statins have anti-inflammatory and bone stimulating properties that may positively affect chronic periodontitis. Our objective in this study was to evaluate whether statin use by chronic periodontitis patients had a beneficial impact on tooth loss. METHODS: In a retrospective cohort study (N patients = 1,021; mean follow-up = 7.1 years), dental records were merged with pharmacy data. Any statin use during 3 years, statin use during each of 3 consecutive years (regular use), and any statin use during the first 3 years after the initial periodontal exam were evaluated as predictors of tooth loss using negative binomial regression models with adjustment for potential confounding factors. RESULTS: Any statin use during 3 years was not associated with tooth loss rate in the year subsequent to the 3-year period (rate ratio [RR] = 1.00; 95% confidence interval [CI] = 0.56 to 1.81). Regular statin use during 3 years was associated with a non-significant 37% reduced tooth loss rate in the year subsequent to the 3-year period (RR = 0.63; 95% CI = 0.32 to 1.25). Any statin use during the first 3 years after the initial periodontal exam was associated with a 48% decreased tooth loss rate in year 4 and subsequent years (RR = 0.52; 95% CI = 0.29 to 0.95). CONCLUSIONS: Our findings were mixed for an association of statin use with reduced tooth loss in chronic periodontitis patients. Lack of control for some potential confounders, particularly smoking, and evaluation of different patterns of statin usage hamper the interpretation of the results. Exploration of these findings in additional epidemiological studies may be worthwhile.

Phenotypic characteristics of adolescents with concave and convex facial profiles - The National Health Examination Survey.

It has been suggested that facial traits are informative on the inherited susceptibility to tuberculosis and obesity, two current global health issues. Our aim was to compare the phenotypic characteristics of adolescents with dental markers for a concave (n=420), a convex (n=978), and a straight (n=3542) facial profile in a nationally representative sample of United States adolescents. The results show that adolescents with a concave facial profile, when compared to a straight facial profile, had an increased waist-to-height ratio (Δ, 1.1 [95% CI 0.5-1.7], p<0.003) and an increased acne prevalence (OR, 1.5 [95% CI 1.2-1.9], p<0.001). Adolescents with a convex facial profile, when compared to a straight facial profile, had an increased prevalence of tuberculosis (OR, 4.3 [95% CI 1.4-13.1], p<0.02), increased ectomorphy (Δ, 0.3 [95% CI 0.2-0.4], p<0.0001), increased left-handedness (OR, 1.4 [95% CI 1.1-1.7], p<0.007), increased color-blindness (OR, 1.7 [95% CI 1.3-2.3], p<0.004), and rhesus ee phenotype (OR, 1.3 [95% CI 1.1-1.5], p<0.008). Adolescents with a concave facial profile, when compared to a convex profile, had increased mesomorphy (Δ, 1.3 [95% CI 1.1-1.5], p<0.0001), increased endomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), lower ectomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), and lower vocabulary test scores (Δ, 2.3 [95% CI 0.8-3.8], p<0.008). It is concluded that population-based survey data confirm that distinct facial features are associated with distinct somatotypes and distinct disease susceptibilities.

Zinc gluconate in the treatment of dysgeusia--a randomized clinical trial.

In the treatment of dysgeusia, the use of zinc has been frequently tried, with equivocal results. The aim of the present randomized clinical trial, which involved a sufficiently large sample, was therefore to determine the efficacy of zinc treatment. Fifty patients with idiopathic dysgeusia were carefully selected. Zinc gluconate (140 mg/day; n=26) or placebo (lactose; n=24) was randomly assigned to the patients. The patients on zinc improved in terms of gustatory function (p <0.001) and rated the dysgeusia as being less severe (p <0.05). Similarly, signs of depression in the zinc group were less severe (Beck Depression Inventory, p <0.05; mood scale, p <0.05). With the exception of the salivary calcium level, which was higher in the zinc patients (p <0.05), no other significant group differences were found. In conclusion, zinc appears to improve general gustatory function and, consequently, general mood scores in dysgeusia patients.

Definitive vs. exploratory periodontal trials: a survey of published studies.

Definitive and exploratory randomized controlled trials (RCTs) have different goals as well as different design and analysis characteristics. The goal of definitive studies is to provide unequivocal evidence of a treatment's tangible benefit to the patient; a pre-trial-specified hypothesis is tested by use of a pre-trial-specified method. The goal of exploratory studies is to elucidate biological treatment mechanisms, to identify promising treatments, and to generate hypotheses for definitive studies; multiple hypotheses are evaluated to extract as much information from the data as possible. The purposes of this study were: (1) to survey selected design and analysis characteristics of randomized controlled periodontal trials published between 1988 and 1992 (n = 86), and (2) to classify trials as exploratory or definitive studies. The peridontal RCTs surveyed were typical of exploratory studies whose primary goal was to elucidate biological treatment mechanisms. Trial reports indicated the testing of multiple hypotheses (> or = 6 hypothesis tests in 70 of the 86 trials) on a variety of biological markers (86 out of 86 trials). The sample size (< or = 30 subjects in 67 out of 86 trials), duration (< or = 6 months in 65 out of 86 trials), and design and analysis characteristics (e.g., an absence of masking in 57 out of 86 trials) were also typical of exploratory studies which strive to obtain quick answers (short duration) at a low cost (small sample size; accept bias for increased efficiency and a lower cost). No definitive trials were identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination and selection of the optimum number of sites and patients for clinical studies.

Calculating required sample sizes is a critical step in the design of any study. For dental studies, the sample size needs to be specified at two levels: (1) the number of patients (n) enrolled in the study, and (2) the average number of sites (m) examined per patient. In general, m and n should be selected in such a way that the precision of the research findings is maximized, while the cost of the study is minimized. This objective can be realized by taking stock of the components of variation and the costs involved with enrolling patients and examining sites. The research cost for n patients ($C1/patient), at an average of m sites per patient ($C2/site), can usually be approximated by nC1 + nmC2. The precision varies as a function of the variance components, m, and n. To optimize precision for a fixed cost, the average number of sites examined per patient (m(opt)) should be approximately equal to [formula: see text] where rho is the within-patient correlation coefficient of the site-specific variable measured. When m(opt) is approximately equal to or in excess of the average number of sites available per patient, whole-mouth examinations are indicated. When m(opt) is considerably smaller than the average number of sites available, the sample of optimum size should be obtained by some random mechanism. Examination of a number of sites considerably different from m(opt) results in a waste of resources, regardless of the number of patients studied. Standard statistical analyses for determination of the patient sample size required to obtain a pre-specified precision or power are discussed.

The utility of the BANA test for monitoring anaerobic infections due to spirochetes (Treponema denticola) in periodontal disease.

Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus each possesses an enzyme(s) that hydrolyzes the synthetic substrate benzoyl-DL-arginine-naphthylamide (BANA). The presence of these organisms in a subgingival plaque sample can be determined by the ability of the plaque to hydrolyze BANA. In the present study, we describe the usefulness of the BANA test at various stages of a clinical trial of the efficacy of metronidazole in the treatment of periodontal disease. A BANA-positive test was significantly associated with high levels and proportions of spirochetes in the plaque, so that it provided information comparable with that which could be obtained by a microscopic examination of the plaque. Patients with such anaerobic spirochetal infections were randomly assigned to a group receiving either metronidazole or placebo (250 mg, three times a day) for one week and whose teeth were scaled and root-planed. The advantages of the decision that metronidazole be used were apparent from the comparison with the results obtained in the patients who received only the scaling and root planing. The initially BANA-positive teeth in the patients treated with metronidazole, scaling, and root planing gained attachment and exhibited a significant reduction in the need for periodontal surgery, when compared with the BANA-positive teeth in the patients who received only placebo, scaling, and root planing. After the conclusion of this therapy, those teeth with persistent BANA-positive plaques had significantly higher proportions and levels of spirochetes than did the teeth with BANA-negative plaques.(ABSTRACT TRUNCATED AT 250 WORDS)

Statistical issues in periodontal research.

In the past 10 to 12 years, there have been several statistical issues identified in periodontal research which require and have generated non-standard or new statistical approaches. The purpose of this paper is to give an overview of these issues and approaches. Three general categories of issues are described: (i) statistical methods for detecting when disease progression occurs, and biological theories and corresponding statistical models which attempt to describe how the disease progresses; (ii) design issues in studies of therapeutic efficacy; and (iii) analytic issues arising from periodontal data analysis.

The effects of simple interventions on tooth mortality: findings in one trial and implications for future studies.

The purpose of this report was to use a particular clinical trial, the Preventive Geriatric Trial (PGT), as a starting point to discuss whether treatment efficacy can be evaluated by means of tooth mortality. In the PGT, 296 subjects were recruited and randomly assigned to five treatment groups: (1) usual procedures (UP); (2) UP + a cognitive-behavioral intervention (CB); (3) UP + CB + weekly chlorhexidine rinse (CHX); (4) UP + CB + CHX + semi-annual fluoride varnish (F); and (5) UP + CB + CHX + F + semi-annual prophylaxis, including scaling (P). Exploratory analyses revealed that tooth mortality after the 1st year was lower in treatment groups 3, 4, and 5 than in groups 1 and 2. A one-year exposure resulted in a 45% reduction in tooth mortality (p < 0.05); a two-year exposure resulted in a 59% reduction (p-value < 0.04). The PGT findings suggested that it is possible to design trials based on clinically relevant endpoints, such as tooth mortality. For the detection of moderate treatment effects, such trials could take the form of Large, Simple Trials (LST), where many subjects are recruited with minimally restrictive entry criteria, and data are collected only on essential baseline characteristics and tooth mortality. LSTs have provided "reliable answers to important clinical questions" for other chronic diseases, and several arguments suggest that they could play a similar critical role in dental research: (1) Periodontitis and caries are among the most common and costly chronic diseases affecting humans, and the identification of even moderately effective treatments by LSTs can have a large socio-economic impact; (2) the identification of low-cost widely practicable treatments that lend themselves to be investigated in LSTs is likely to benefit more people than the identification of high-cost complex treatments; and (3) tooth mortality is simple to assess and more relevant than the unvalidated surrogate endpoints that have largely failed for more than 20 years to provide reliable answers to certain controversial issues regarding treatment efficacy. The cost of not reliably establishing the safety and the efficacy of treatments may be far greater than the cost of conducting LSTs.

Efficiency issues among statistical methods for demonstrating efficacy of caries prevention.

Although repeated tooth-surface-specific information is commonly collected during a longitudinal caries clinical trial, traditional methods often make limited use of the repeated measures. Newer methods of analysis, such as methods based on time-to-event and methods for longitudinal or clustered data, have the potential to increase the efficiency of the statistical analysis. We compare a range of analytical methods from the traditional analysis based only on the number of caries onsets to newer methods that incorporate time at risk and surface-specific information, such as Poisson regression methods for clustered data, with respect to the efficiency of treatment comparisons. Under most circumstances, the greatest gain in efficiency associated with time-to-event methods will be due to the ability of subjects to contribute caries onsets to the analysis until they are lost from the study. Incorporating the number of surfaces at risk, the surface time at risk, and surface-specific characteristics will typically produce only a modest gain in efficiency.

Bias induced by self-reported smoking on periodontitis-systemic disease associations.

Non-causal associations between periodontitis and systemic diseases may be spuriously induced by smoking because of its strong relationship to both. The goal of this study was to evaluate whether adjustment for self-reported smoking removes tobacco-related confounding and eliminated such spurious confounding. Using NHANES III data, we evaluated associations between attachment loss and serum cotinine after adjustment by self-reported number of cigarettes smoked. Cotinine, a metabolite of nicotine, should not be related to attachment loss, if self-reported smoking captures the effect of tobacco on attachment levels. Adjustment for self-reported cigarette smoking did not completely remove the correlation between attachment loss and serum-cotinine level (r = 0.075, n= 1507, p = 0.003). Simulation studies indicated similar results for time-to-event data. These findings demonstrate the difficulty in distinguishing the effects of periodontitis from those of smoking with respect to a smoking-related outcome. Future studies should report results of analyses on separate subcohorts of never-smokers and smokers.

Pre-existing cardiovascular disease and periodontitis: a follow-up study.

Periodontal infections in individuals with pre-existing heart disease are believed to increase the risk for future coronary heart disease (CHD) events. The goal of this study was to search for an association between periodontitis and CHD events among individuals with pre-existing heart disease, reported in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Dentate adults (n = 636) with a history of pre-existing cardiovascular disease were followed for CHD events. The presence of periodontitis and gingivitis did not increase CHD risk among these at-risk individuals (hazard ratio [HR], 0.97, and 95% confidence interval [CI], 0.72-1.31; and HR, 1.09, and 95% CI, 0.79-1.50, respectively). When limited to individuals with a self-reported prior heart attack, periodontitis was associated with a 34% decreased CHD risk (HR, 0.66; 95% CI, 0.42-1.05). It is concluded that periodontitis or gingivitis does not elevate CHD risk among individuals with a prior heart attack or self-reported pre-existing cardiovascular disease.

Within-subject coronal caries distribution patterns: an evaluation of randomness with respect to the midline.

The distribution of caries among homologous surfaces can exhibit three possible patterns: random, aggregated, or regular. In a random caries pattern, caries lesions are randomly distributed among homologous surfaces. An aggregated caries pattern is distinguished by the aggregation of lesions on one side of the mouth or the other to a greater extent than would be expected by chance alone. For a regular caries pattern, the left-right distribution of lesions is more homogenous than would be expected by chance alone. A test statistic based on the left-right distribution of caries lesions among discordant homologous pairs was developed to investigate which of these three caries patterns is present in a representative sample of the adult United States population. The data originated from the National Survey of Oral Health in the US (Employed Adults), 1985-1986. Of the 15,132 subjects studied, 12,776 subjects had 2 or more decayed or filled teeth. (At least 2 carious or filled teeth are required for detection of patterns.) Approximately 50% of these subjects (n = 6,439) had two or more discordant homologous tooth pairs. With these tooth pairs, the hypothesis of a random caries pattern was rejected in favor of an aggregated caries pattern (p < 0.0001). Similar findings were obtained with discordant homologous surface pairs. This aggregation of caries on one side of the mouth or the other may be due to genetic, infectious, and/or environmental factors.