Current concepts and an alternative perspective on periodontal disease.

BACKGROUND: Epidemiological data from countries worldwide show a consistent pattern implying that a fraction of around 10% of those over 40-50 years in all populations will exhibit severe periodontitis with the potential risk of losing teeth during their life-time. The subgingival microbiota shows striking similarities between populations irrespective of disease severity and can only marginally explain the clinical pattern. It is also difficult to explain this pattern by genetic and acquired risk factors such as systemic disease (e.g. diabetes) or habits (e.g. smoking) even if they may have a confounding effect on the disease. MAIN TEXT: Inflammation of the gingiva appears to be a normal and physiological response to the presence of commensal bacteria along the gingival crevice and in the dental biofilm. Over many years of exposure to the dental biofilm, the chronic inflammation in the gingiva gradually results in a loss of attachment and bone loss. Numerous laboratory and clinical studies have provided insight into the potential role of determinants that are associated with periodontitis. However, it has been difficult to relate the findings to the pattern of the distribution of the disease observed in epidemiological studies. We propose a simple and parsimonious model that considers all the multitude of potential determinants as creating effectively random noise within the dental biofilm to which the tissues react by accumulating the effects of this noise. CONCLUSIONS: We suggest that such a model can explain many of the epidemiological features of periodontal breakdown over time, and we discuss its clinical implications.

Caries and Periodontitis: Contesting the Conventional Wisdom on Their Aetiology.

We review the literature on the oral microbiome and the role of the microbiota in the development of dental caries and periodontitis. While most research has been focused on identifying one or more specific determinants of these diseases, the results have provided limited predictive value and have not been able to explain the variation in the distribution of these diseases observed in epidemiological or clinical studies. Drawing on existing knowledge about the nature of the oral microbiota, we suggest that a stochastic model based on the Weiner process provides simple and parsimonious explanations for the pathogenesis of both caries and periodontitis, making few assumptions, and providing explanations for phenomena that have hitherto proved difficult, or have required complex arguments, to explain. These diseases occur as the result of the dental hard tissues and periodontal tissues integrating the random "noise" caused by normal metabolic activities of commensal microorganisms in the dental biofilm. The processes that result in the progression and regression of caries and periodontitis may be considered as "natural," rather than pathological, even if, when left unchecked over long periods of time, they can result in the development of pathologies. The likelihood of progression or regression can be influenced by other determinants, but these processes will nevertheless occur in the absence of such influences. The distributional characteristics of the model approximate the findings of epidemiological studies indicating that, for both caries and periodontitis, there will be few sites affected in the early period after the eruption of the permanent dentition, but in those older there is an almost linear relationship with increasing age; furthermore, the longer a site survives without being affected, the less likely that it will be affected. We discuss the clinical and public health importance of these findings.

Subgingival bacterial clusters and serum antibody response as markers of extent and severity of periodontitis in adult Chinese.

This study evaluated the associations between clinical, microbiological, and antibody activity manifestations of periodontitis in 123 adult rural Chinese subjects with no dental intervention. All participants were registered for full-mouth clinical attachment level (CAL) and pocket probing depth (PD) measurements, and microbial samples were taken from four sites and analyzed for 18 different bacterial species using the 'checkerboard'. Serum from each individual was analyzed to determine the antibody activity against the same 18 species. Exploratory factor analysis disclosed two microbial factors - Factor 1, consisting of seven species associated with periodontal health ('early colonizers'); and Factor 2, consisting of eight species associated with periodontitis ('putative periodontopathogens') - which explained 87% of the variation among the microbial variables. Factor 2 was consistently associated with disease-severity measures, whereas the 'early colonizer' factor was not. The antibody response showed weak or no correlations with bacterial load or with disease severity. We conclude that the bacteria investigated are resident in the subgingival plaque; that their load and proportions in the pocket may be ecologically driven; and that the antibody response is based on bacterial carrier state rather than on disease. The different antibody-response pattern found between the individuals may suggest that each individual could be classified as a good or a weak immune responder.

Infected Dentine Revisited.

Dentine becomes infected as a result of caries lesion formation on root surfaces and when lesions progress following cavitation of enamel lesions. However, this infection is unimportant because the driving force for lesion formation and progression is the overlying biofilm. This explains why root surface caries can be controlled by mechanical plaque control and fluoride, and restorations are not needed to arrest these lesions. Similarly, the infected dentine in cavitated coronal lesions does not have to be removed to arrest the lesion. If the lesion is either accessible or opened for cleaning by the patient or parent, the lesion can be arrested. Sealing of infected dentine within the tooth, either by a Hall crown in the primary dentition or by partial caries removal prior to placing a well-sealed filling, will also arrest the lesion. When restoring deep lesions in symptomless, vital teeth, vigorous excavation of infected dentine is likely to expose the pulp and make root canal treatment necessary. Thus complete excavation'is not needed and should be avoided. CPD/CLINICAL RELEVANCE: Root surface caries can be arrested by cleaning and fluoride application. Restorations are not essential. Vigorous excavation of softened dentine in deep cavities of symptomless, vital teeth is contra-indicated. It is not needed and increases the risk of pulp exposure.

Changing concepts in cariology: forty years on.

UNLABELLED: The caries lesion is a sign or symptom resulting from numerous pH fluctuations in biofilms on teeth. The lesion may or may not progress and lesion progression can be controlled, slowed down or arrested. Control of the biofilm is the treatment of caries, the most important measure being to disturb the biofilm mechanically using a fluoride-containing toothpaste. The informed patient controls caries and the role of the dental professional is to advise how this should be done. This is the non-operative treatment of caries and it is worthy of payment. It should be mandatory as part of any operative treatment to ensure that the patient understands, and is able to perform, adequate plaque control. CLINICAL RELEVANCE: It is very unfortunate that the current remuneration scheme (Unit of Dental Activity) in Health Service practice in England and Wales prevents practitioners adopting a modern biological approach to caries control.

Targeted disruption of the Cl-/HCO3- exchanger Ae2 results in osteopetrosis in mice.

Osteoclasts are multinucleated bone-resorbing cells responsible for constant remodeling of bone tissue and for maintaining calcium homeostasis. The osteoclast creates an enclosed space, a lacuna, between their ruffled border membrane and the mineralized bone. They extrude H(+) and Cl(-) into these lacunae by the combined action of vesicular H(+)-ATPases and ClC-7 exchangers to dissolve the hydroxyapatite of bone matrix. Along with intracellular production of H(+) and HCO(3)(-) by carbonic anhydrase II, the H(+)-ATPases and ClC-7 exchangers seems prerequisite for bone resorption, because genetic disruption of either of these proteins leads to osteopetrosis. We aimed to complete the molecular model for lacunar acidification, hypothesizing that a HCO(3)(-) extruding and Cl(-) loading anion exchange protein (Ae) would be necessary to sustain bone resorption. The Ae proteins can provide both intracellular pH neutrality and serve as cellular entry mechanism for Cl(-) during bone resorption. Immunohistochemistry revealed that Ae2 is exclusively expressed at the contra-lacunar plasma membrane domain of mouse osteoclast. Severe osteopetrosis was encountered in Ae2 knockout (Ae2-/-) mice where the skeletal development was impaired with a higher diffuse radio-density on x-ray examination and the bone marrow cavity was occupied by irregular bone speculae. Furthermore, osteoclasts in Ae2-/- mice were dramatically enlarged and fail to form the normal ruffled border facing the lacunae. Thus, Ae2 is likely to be an essential component of the bone resorption mechanism in osteoclasts.

Ion transporters in secretory and cyclically modulating ameloblasts: a new hypothesis for cellular control of preeruptive enamel maturation.

Mature enamel consists of densely packed and highly organized large hydroxyapatite crystals. The molecular machinery responsible for the formation of fully matured enamel is poorly described but appears to involve oscillative pH changes at the enamel surface. We conducted an immunohistochemical investigation of selected transporters and related proteins in the multilayered rat incisor enamel organ. Connexin 43 (Cx-43) is found in papillary cells and ameloblasts, whereas Na(+)-K(+)-ATPase is heavily expressed during maturation in the papillary cell layer only. Given the distribution of Cx-43 channels and Na(+)-K(+)-ATPase, we suggest that ameloblasts and the papillary cell layer act as a functional syncytium. During enamel maturation ameloblasts undergo repetitive cycles of modulation between ruffle-ended (RA) and smooth-ended (SA) ameloblast morphologies. Carbonic anhydrase II and vacuolar H(+)-ATPase are expressed simultaneously at the beginning of the maturation stage in RA cells. The proton pumps are present in the ruffled border of RA and appear to be internalized during the SA stage. Both papillary cells and ameloblasts express plasma membrane acid/base transporters (AE2, NBC, and NHE1). AE2 and NHE1 change position relative to the enamel surface as localization of the tight junctions changes during ameloblast modulation cycles. We suggest that the concerted action of the papillary cell layer and the modulating ameloblasts regulates the enamel microenvironment, resulting in oscillating pH fluctuations. The pH fluctuations at the enamel surface may be required to keep intercrystalline spaces open in the surface layers of the enamel, enabling degraded enamel matrix proteins to be removed while hydroxyapatite crystals grow as a result of influx of calcium and phosphate ions.

Prevalence and extent of dental caries, dental fluorosis, and developmental enamel defects in Lithuanian teenage populations with different fluoride exposures.

The aim of this study was to describe the pattern of dental caries, dental fluorosis, and developmental defects of non-fluoride origin in Lithuanian children born and raised in regions with 1.1 ppm (1.1 mg/l F) and 0.3 ppm (0.3 mg/l F) water fluoride levels, respectively. All permanent surfaces/teeth of 300 teenagers were examined for dental caries, dental fluorosis, and non-fluoride developmental defects. The caries prevalence of the study population was 100%. The mean number of decayed surfaces (DS) differed only slightly and statistically insignificantly between the '1.1 ppm fluoride' and '0.3 ppm fluoride' groups (19.6 and 18.1, respectively). However, a greater number of inactive lesions and fewer fillings were found in the '1.1 ppm fluoride' group than in the '0.3 ppm fluoride' group (mean difference 1.18 and -2.80, respectively). The prevalence of dental fluorosis was 45% and 21%, respectively; the prevalence of non-fluoride opacities was 8% and 19%, respectively; and the prevalence of hypoplasia was 12% and 16%, respectively, in the '1.1 ppm fluoride' and '0.3 ppm fluoride' groups. Higher caries levels were noted in children with no fluorosis compared to those with fluorosis recorded (mean DS difference, 3.43). The results lend support to the hypothesis that the presence of fluoride in the oral environment promotes lesion arrest rather than inhibiting the initiation of new lesions.

Diagnosing dental caries in populations with different levels of dental fluorosis.

The aim of this study was to assess the reliability of the Nyvad visual-tactile caries-diagnostic criteria when used among children who have been lifelong residents in areas with 'optimal' or low concentrations of fluoride in the drinking water. In each of two areas with drinking water fluoride concentrations of 0.3 and 1.1 ppm (0.3 and 1.1 mg/l) fluoride, respectively, 150 children were clinically examined twice, 2 wk apart, for dental fluorosis, using the Thylstrup-Fejerskov index (TF index), and for dental caries using the Nyvad visual-tactile caries criteria. The prevalence of dental fluorosis was 45% in the 1.1 ppm fluoride area and 21% in the 0.3 ppm fluoride area. When the results of the duplicate caries recordings were compared at the surface level, only minute differences were observed in the percentage agreement (91.7 and 90.7%, respectively) and in the kappa values (0.73 and 0.72, respectively). When individual DFS counts were compared across examinations using Bland-Altman plots and estimation of prediction intervals for the differences, we observed a greater variability of the differences between recordings among children from the low-fluoride area. Contrary to our expectations, a pronounced dental fluorosis background did not reduce the reliability of the caries recordings, which appeared to be slightly less reliable at very low levels of dental fluorosis.

[Novel treatment possibilities for proximal caries]. / Neuartige Therapiemöglichkeiten bei approximaler Karies.

So far approaches for caries treatment follow a dichotomized scheme: Non invasive options of primary and secondary prevention are contrasted to invasive treatment of caries lesions. Depending on the treatment philosophy of dentists and dental schools an early or late invasive treatment threshold is recommended. Sealing of proximal lesions as done in pit and fissures has only been established in some dental schools, so far. Moreover, infiltration of the enamel part of lesions could close the gap between preventive and invasive measures. Most of these novel treatment options for proximal surfaces are currently in the last stages of product development. With respect to the good clinical results of proximal sealing with conventional sealants, this regimen seems already be recommendable to hamper further lesion progression in clinical practice. Caries infiltration of lesions situated on proximal and other smooth surfaces might even be a more promising approach, if clinical studies corroborate the recent in vitro findings. All these novel limited invasive strategies might be suitable to complete the current dichotomized way of caries treatment.

Root Surface Caries - Rationale Behind Good Diagnostic Practice.

Root surfaces, which with increasing age become exposed to dental biofilms, will react to the intermittent pH fluctuations at the interface between the biofilm and the cementum/dentin surface. If dental biofilm is left undisturbed in stagnation sites in the dentition, the underlying mineral surfaces may gradually develop dental caries characterized by a subsurface loss of mineral. In root surfaces, the demineralization is accompanied by microbial invasion of the cementum and dentin resulting in a pulpo-dentinal defense reaction. Most lesions progress slowly and experimental in situ studies as well as clinical studies document that the daily removal of the biofilm using fluoride toothpaste can arrest lesion progression. By applying this caries control measure, caries lesions can thus be transformed from active lesions to inactive lesions. The diagnostic characteristics of these types of lesions are mandatory to apply in daily clinical practice to avoid unnecessary restorative and antimicrobial treatments.

Fluctuations in surface pH of maturing rat incisor enamel are a result of cycles of H(+)-secretion by ameloblasts and variations in enamel buffer characteristics.

It is disputed if ameloblasts in the maturation zone of the enamel organ mainly buffer protons released by hydroxyapatite (HA) crystal growth or if they periodically secrete protons to create alternating acidic and alkaline conditions. The latter hypothesis predicts alternating pH regimes in maturing enamel, which would be affected by pharmacological interference with ameloblast H(+)-secretion. This study tests these predictions. Colorimetric pH-indicators and ratiometric fluorometry were used to measure surface pH in maturation zone enamel of rat incisors. Alternating acidic (down to pH6.24±0.06) and alkaline zones (up to pH7.34±0.08) were found along the tooth coinciding with ameloblast morphological cycles. Underlying the cyclic pattern, a gradual decrease in pH towards the incisal edge was seen. Vinblastine or FR167356 (H(+)-ATPase-inhibitor) disturbed ameloblast acid-secretion, especially in the early parts of acidic zones. Enamel surface pH reflects the titration state of surface PO4(3-)-ions. At the pH-values observed, PO4(3-) would be protonated (pKa>12) and HA dissolved. However, by molecular dynamics simulations we estimate the pKa of HPO4(2-) at an ideal HA surface to be 4.3. The acidic pH measured at the enamel surface may thus only dissolve non-perfect domains of HA crystals in which PO4(3-) is less electrostatically shielded. During repeated alkaline/acidic cycles, near-perfect HA-domains may therefore gradually replace less perfect HA-domains resulting in near-perfect HA-crystals. In conclusion, cyclic changes in ameloblast H(+)-secretion and the degree of enamel maturation determine enamel surface pH. This is in accordance with a hypothesis implicating H(+)-ATPase mediated acid-secretion by ameloblasts.