Published literature was reviewed and screened systematically, and eight studies met the criteria for the high-quality category. The evidence for each element inferring a causal association between smoking and tooth loss in high-quality studies was summarised and evaluated on the basis of standardised methodologies with respect to consistency and study design. The evidence supporting this causal association was consistent. The association cannot be explained by confounding factors. Several concerns regarding the reporting of the synthesis of evidence will be addressed before the final description of the overall evidence.
First, the validated association in the epidemiologic literature should be biologically plausible. The most plausible biological connection between substances in tobacco smoke and tooth loss is the destruction of tooth-supporting tissue. Previous studies have shown several pathways on the basis of exisisting knowledge of the effects on the entire body of smoking [1
]. These include dysfunction of gingival fibroblasts, a decrease in microcirculatory function and immune system deficiency. Periodontal destruction in smokers may be modulated by an impaired ability to repair damaged tissue rather than by direct tissue damage. Recent progress in molecular and genetic approaches have made a deeper exploration of the mechanisms possible [29
]. In a previous study, smokers exhibited overproduction of inflammatory molecules and suppression of anti-inflammatory molecules, thereby leading to inflammatory destruction of connective tissue and alveolar bone, though evidence of interaction with genetic factors is inconsistent.
A series of recent studies [30
] revealed a bacteriological mechanism by utilising a novel methodology for bacterial identification. The microbial profile of disease-associated and health-compatible organisms in smoking-associated periodontitis patients was significantly different from that in non-smokers. Following nonsurgical periodontal therapy and smoking cessation counselling, those who continued smoking had a microbial profile similar to the baseline, while the subgingival microbiome in those who stopped smoking exhibited a healthy profile. These findings explain the connection between smoking and periodontal tissue breakdown by pathogenic periodontal micoorganisms.
The effects of several chemicals in tobacco smoke on the immune system and tissue repair in relation to periodontal tissue breakdown have been reported [1
]. Nicotine, benzo(a)pyrene and benzo(a)anthracene are immunosuppressive, whereas tobacco glycoprotein and metals are immunostimulatory. Exposure to hydrocarbons could modulate immune response. Nicotine and some other tobacco compounds such as acrolein and acetaldehyde inhibit the function of gingival fibroblasts, including proliferation, collagen production, adhesion to root surfaces and induce cytotoxicity. Together, the substantive evidence strongly supports the biological plausibility of these effects.
The NOS evaluated the methodological considerations for various biases, but other sources may be considered. Early death in current smokers that have lost more teeth than non-smokers could dilute the effect of smoking in the elderly, particularly in studies that employ total tooth loss as the outcome measure. Only one study reported the dropout rate in the entire cohort population [24
], and no other study accounted for the possibility of participation bias between comparison groups in identical cross-sectional samples. Smokers with fewer teeth may not have participated in the study compared with non-smokers with more teeth, leading to the underestimation of the effect of smoking.
Publication bias based on the finding of a significant association is inevitable in a literature review. Although associations between smoking and tooth loss were focused on in five high-quality studies, three other studies that reported significant associations examined various other factors, which may weaken the existence of a publication bias.
In Japanese studies, 20 existing teeth or more was used as the definition of tooth loss [16
], because '20 existing teeth till 80 years' was set as an objective of the national oral health promotion programme. A definition based on malfunction may more accurately reflect the risk of smoking than one lost tooth or total tooth loss. In a cross-sectional study, the 15th percentile for each age group was employed as the definition of tooth loss [27
]. This method may help to decrease heterogeneity in the definition of tooth loss due to differences in study populations in terms of the variety of tooth-loss profiles. Study funding can also be an important source of heterogeneity, but all studies were supported by public or quasi-public grants.
Distribution of the level of exposure within groups of current or former smokers may vary according to the study population; for example, health professionals may have stopped smoking many years ago [24
]. Observed differences in effect size could be explained in part by the difference in distribution of exposure level. The results reported for populations in four countries where smoking has been prevalent strongly support a causal association at the population level. Because effects of smoking generally appear in later life, reports from countries where smoking rates are increasing are expected. Unfortunately, reports from such countries were excluded due to concerns regarding methodological quality (data not shown). Further studies with high-quality methodology that use data from populations in countries where smoking rates are increasing are necessary.
In the present review of cross-sectional studies, qualitative evaluation was based on differences in the prevalence of tooth loss. Because the difference in prevalence was not adjusted for any possible confounder, the results of qualitative evaluation should be interpreted carefully. For example, the lack of adjustment for age underestimates differences in the prevalence of tooth loss because of the increasing prevalence of tooth loss in a decreasing number of current smokers with age. The hazard ratio, which considers the observational period of each case in a cohort study, is the most accurate indicator of the effect size [23
]. We did not use unpublished material and articles written in languages other than English or contact authors of original studies. The effect sizes in two studies were represented by the data of specific categories. These issues may be limitations on the interpretation of the abstracted data.
Randomised controlled studies are scarce because of difficulties associated with smoking cessation and the need for long-term observations. Natural experiments on the decreased risk in former smokers over time after stopping smoking could provide reliable secondary evidence of causal associations in observational studies. Cohort studies have revealed that longer periods of smoking cessation are associated with a lower risk of tooth loss in a dose-response manner [23
]. The findings of a decreasing risk of tooth loss with increasing time since stopping smoking may strengthen the interpretation of causal association. Further studies with data obtained from longitudinal cohorts should be conducted among populations from countries other than the United States.