Review of 36,537 patient records for tooth health and longevity of dental restorations.

To develop an automatic system for utilizing electronic dental records, a data mining system to extract the diagnostic and treatment codes from the records for an intermediate file and automatic drawing of Kaplan-Meier-type survival curves was first created. Then this intermediate file was analyzed with SAS software for the scientific determination of Kaplan-Meier survival of tooth/surface-specific healthy time and survival of restorations in each permanent tooth, health center, and age cohort and also combined. All patients born in 1985, 1990 or 1995 in 28 health centers in Finland were analyzed. Patients classified as caries-active were those who had caries in any first permanent molar under the age of 8 years, while resistant patients did not have caries in these teeth before 10 years. In the younger age cohorts, a shortening of survival of caries-free teeth was seen. The shortest caries-free survival was seen in mandibular and maxillary molars in the youngest age cohort. Occlusal surfaces of molars determined their caries onsets and proximal caries occurred equally in molars, incisors and premolars, whereas canines or mandibular incisors did not have caries in these age cohorts. Caries-prone subjects had the shortest survival in all their teeth. The median longevity of all restorations was 11.7 years, with great variation between health centers and teeth. Because of the great variation between individual teeth, the tooth-specific approach seems appropriate in both caries epidemiology and material sciences.

Has dental caries prevalence some connection with caries index values in adults?

DMF index values have been used for 70 years and were originally meant to describe both dental status and treatment need in elementary school children. Since then its application to caries experience and severity determination has expanded. Today, WHO has standardized its use in oral health surveys in describing past and present caries experience in adults and the elderly as well. This expansion to all age cohorts creates some problems if the index is limited to dental caries, which can be easily avoided when individual values are not combined. This has been performed in some of the 7,187 DMF index publications included in PubMed. The high number of scientific articles using this index underlines its leading role in the present epidemiological caries research. On the other hand, WHO uses different determinations for clinical dental caries and missing teeth in ICD-10, the 10th revision of International Classification of Diseases, which does not include dental restorations. Combining the individual parameters of Oral Health Surveys and diseases of ICD-10, and analyzing the mean value of each parameter separately, will give a precise picture of dental health at different ages.

A practice-based study of the variation of diagnostics of dental caries in new and old patients of different ages.

Data mining of digital dental records provides possibilities for analysing the variation between dentists when diagnosing caries. A total of 71,317 male and 82,302 female subjects visited the health centres in Vantaa and Kemi during the 'digital era' (1994-2005). As subjects were classified as 'new patients' at the first examination, all re-examinations of the same subjects thereafter by the same dentist produced 'old patients'. A mean number of decayed surfaces (DS) was counted as a function of the age of the subject during the follow-up. The significance of the difference between old and new patients was determined by the Mann-Whitney test for each age cohort at the cross sections, and for the whole follow-up. Caries was seen to affect new patients more than the old ones in both health centres after the age of 20 years. The mean DS values were the same, reaching about 1 for new and old patients at the age of 15 years. The mean DS had a peak for new patients in both health centres at the age of 25 years and another peak around 45-50 years in Kemi. With a few exceptions there was a significant difference between the DS values of new and old patients at most cross sections and for the whole follow-up time. Evidently dentists examine new patients more carefully than their old patients. After the age of 18 years patients may have changed their dentists because they have finished the free-of-charge treatment period.

Long-term predictive value of salivary microbial diagnostic tests in children.

AIM: To investigate in a group of children (n=183) the predictive value of early colonization of salivary lactobacilli and candida on caries development in primary molars and permanent first molars in 7 years of follow-up time by applying a longitudinal survival analysis method. STUDY DESIGN: Longitudinal cohort study of clinical outcomes based on dental records. METHODS: The Kaplan-Meier survival analysis method was used to compare survival times to caries onset in primary molars and permanent first molars for children colonized by salivary lactobacilli and candida and children who were not colonized by those microbes at baseline when children's mean age was 2.5 years. The survival time was the time elapsing between the birth of a child and the first restoration as a result of dental caries, that is the time when caries has progressed to a stage when a dentist has made a decision to restore the affected tooth. RESULTS: The survival curves for primary and permanent molars were consistently lower for those children whose mouths were colonized by salivary lactobacilli at baseline. A statistically significant relationship was found with onset of caries in both primary and permanent molars and colonization by salivary lactobacilli. The survival of primary second molars was 60% at the age of 9 years in the group colonized by lactobacilli and 80% in those children whose mouths were not colonized. Colonization by candida was also a significant risk factor for caries onset in primary molars but not in permanent first molars. CONCLUSION: Children whose mouths were colonized by salivary lactobacilli at baseline were more susceptible to caries onset in both primary and permanent molars at any given time during follow- up of seven years than children who were not colonized by those caries associated microorganisms.

Tooth by tooth survival analysis of dental health in girls with epilepsy.

AIM: The aim of this study was to analyse, tooth by tooth, the timing of caries attacks leading to dental restoration in girls with epilepsy. STUDY DESIGN: The series comprised 60 girls with epilepsy, 8-18 years old, treated in the Departments of Paediatrics or Neurology of the Oulu University Hospital. A group of healthy age matched girls served as control. METHODS: A tooth by tooth survival analysis of the time between tooth eruption and caries attacks to a stage leading to the restorations of the permanent teeth was conducted retrospectively using data from the dental health records with annual examinations. RESULTS: The rate of dental restorations placed due to caries was constantly higher in the girls with epilepsy than in their controls. STATISTICS: The difference was significant between the first molars (p=<0.03), second molars (p=<0.02) and central incisors (p=<0.02) in the maxilla. CONCLUSION: The present observation supports the hypothesis that factors related to epilepsy, the antiepileptic medication in particular, might increase the risk of caries.

Caries occurrence in a fluoridated and a nonfluoridated town in Finland: a retrospective study using longitudinal data from public dental records.

The tap water of Kuopio, Finland, was fluoridated from 1959 to 1992. In the first decade of fluoridation, children in Kuopio had lower DMF values than children in Jyväskylä, a nearby low-fluoride town, but later differences between the towns have been small and inconsistent. The present study aimed to gain further insight into caries occurrence in Kuopio and Jyväskylä using longitudinal tooth-specific data from public health records on cohorts born in 1970/71 and 1980/81 (total n = 1,503). Survival analyses were used to summarize the tooth-specific times elapsed between eruption and the first filling (used as a proxy for dental caries). Generally, the first filling was placed sooner after eruption in the 1970/71 cohort than in the 1980/81 cohort. The curves for the two towns were virtually identical except for the first molars of the 1970/71 cohort, for which the percentage of filled first molars was consistently lower in Jyväskylä than in Kuopio. This study indicates that, among children and adolescents whose permanent teeth erupted in the mid-1970s or thereafter, even a longitudinal approach did not reveal a lower caries occurrence in the fluoridated than in the low-fluoride reference community. The main reason for the modest effect of water fluoridation in Finnish circumstances is probably the widespread use of other measures for caries prevention. The children have been exposed to such intense efforts to increase tooth resistance that the effect of water fluoridation does not show up any more. The results must not be extrapolated to countries with less intensive preventive dental care.

The localization of matrix metalloproteinase-20 (MMP-20, enamelysin) in mature human teeth.

MMP-20 (enamelysin), the matrix metalloproteinase family member discovered in the enamel organ, has also been detected in odontoblasts during dentin formation. We studied the presence and localization of MMP-20 in mature human teeth in health and disease. In immunohistochemistry, MMP-20-positive staining was observed most intensively in the radicular odontoblastic layer and also in dilated dentinal tubuli of caries lesions. By Western blotting, MMP-20 was detected in odontoblasts and pulp tissue of both sound and carious teeth, in dentinal fluid and dentin of sound teeth, but not in soft carious dentin. We conclude that MMP-20 produced during primary dentinogenesis is incorporated into dentin and may be released during caries progression. The main cellular source of MMP-20 in the dentin-pulp complex is the odontoblasts, which secrete MMP-20 into the dentinal fluid.

Regulation and interactions of MT1-MMP and MMP-20 in human odontoblasts and pulp tissue in vitro.

MT1-MMP is a cell-membrane-bound metalloenzyme that activates other proMMPs such as proMMP-2 and -13. We studied MT1-MMP expression in mature human odontoblasts and pulp tissue, the regulation of MT1-MMP expression by growth factors TGF-beta1 and BMP-2, and the activation of odontoblast-derived MMP-20 by MT1-MMP. MT1-MMP mRNA is expressed by native and cultured mature human odontoblasts and pulp tissue. Western blot analysis of human odontoblasts and pulp tissue detects 65- and 51-kDa pro- and active forms of MT1-MMP, and smaller truncated MT1-MMP forms. BMP-2 down-regulates MT1-MMP expression in odontoblasts and pulp tissue, while TGF-beta1, alone or with BMP-2, decreases MT1-MMP mRNA levels only slightly. We also demonstrate that MT1-MMP is capable of converting proMMP-20 into a form corresponding to the active MMP-20. In conclusion, this study demonstrates the expression and differential regulation of MT1-MMP in human dentin-pulp complex cells, and the activation of MMP-20 by MT1-MMP.

The effect of a high-sucrose diet on dentin formation and dental caries in hyperinsulinemic rats.

A high-sucrose diet decreases dentin formation and its minerals, but the mechanisms behind the effect are largely unknown. We studied the combined and separate effects of sucrose and insulin on dentin formation and mineral metabolism in growing rats. At weaning, animals were randomized into 4 groups: control/sucrose diets both with and without external insulin (1 U/x 100 g body weight daily). After 4 weeks, we measured areas of dentin formation, numbers and areas of dentinal caries lesions, and serum and urine glucose, insulin, Ca, Na, K, and P. Exogenous insulin increased serum and urine insulin levels and decreased serum glucose level, but did not affect dentin formation or dentinal caries lesion formation or progression. A high-sucrose diet decreased dentin formation independently of insulin. The differences in serum and urine minerals between the groups were minor. The findings confirm that sucrose-diet-induced reduction in dentinogenesis is independent of insulin and loss of minerals in urine.

Applying modern survival analysis methods to longitudinal dental caries studies.

Before the 1960s, tooth-specific caries risk was reported to be highest at 2 to 4 years after eruption. We studied the tooth-specific caries risk in three contemporary age cohorts in Finland. All together, 4072 boys and girls were followed annually from age 6 to age 18+ years in three age cohorts born in the 1960s, 1970s, and 1980s. We used a survival model and Bayesian inferential methods in the statistical analyses to establish the secular changes during this period. The analysis was based on the caries risk in individual teeth as a function of tooth age instead of summary measures, such as DMFS values. Our first finding was a marked overall decrease of caries. Moreover, analyses of the 1960 and 1970 cohorts revealed that the risk in molar teeth was highest immediately after eruption; in the youngest cohort, however, the risks of individual teeth were so low that no such dependencies on tooth age could be established.

The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats.

Previous studies suggest that salivary and pulp-derived host enzymes, matrix metalloproteinases (MMPs), may be involved in dentin caries pathogenesis. To study the inhibition of acid-activated human salivary MMPs by non-antimicrobial chemically modified tetracyclines (CMTs), we used a functional activity assay with 125I-labeled gelatin as a substrate. To address the role of MMPs in the progression of fissure caries in vivo, we administered the MMP inhibitors CMT-3 and zoledronate to young rats per os for 7 weeks, 5 days a week. Caries lesions were visualized by Schiff reagent in sagittally sectioned mandibular molars. Marked reduction in gelatinolytic activity of human salivary MMPs was observed with CMT-3. CMT-3 and zoledronate, both alone and in combination, also reduced dentin caries progression in the rats. These results suggest that MMPs have an important role in dentin caries pathogenesis, and that MMP inhibitors may prove to be useful in the prevention of caries progression.

High-sucrose diet reduces defensive reactions of the pulpo-dentinal complex to dentinal caries in young rats.

The significance of systemic dietary effects on the response of the pulpo-dentinal complex to dentinal caries was examined. Weanling rats were divided into high sucrose or control diet groups both with and without cariogenic bacterial inoculation. At the onset, tetracycline was injected to mark the dentin formation during the experiment. After 5-6 week, mandibular molars were sectioned sagittally. The areas of dentin formed during the experiment and those of dentinal caries were quantified separately in the first and second molars. In the control diet groups the area of dentin was significantly greater under carious fissures, whereas in the high sucrose diet groups the area of dentin formed did not differ between intact and carious fissures. The high sucrose diet resulted in a significantly smaller area of dentin formation than did the control diet. The high sucrose diet with cariogenic bacterial inoculation resulted in the greatest area of dentinal caries. With the control diet a positive response against dentinal caries occurs, but the high dietary sucrose content impairs the defensive reactions of pulpo-dentinal complex against dentinal caries. These findings add further evidence of the importance of the local endogenous factors of caries progression.

Baseline expression and effect of TGF-beta 1 on type I and III collagen mRNA and protein synthesis in human odontoblasts and pulp cells in vitro.

Since growth factors have been suggested to regulate dentin collagen formation in response to external irritation, we investigated the effect of TGF-beta 1 on pro alpha 1 (I) collagen mRNA expression in cultured mature human odontoblasts and pulpal fibroblasts, as well as cultured human pulp tissue, using quantitative PCR. Cultured gingival fibroblasts (GF) and osteoblasts (OB) served as controls. Also, type I collagen synthesis in cultured odontoblasts and pulp tissue, as well as type III collagen synthesis in odontoblasts, were studied by measuring respective procollagen (PINP and PIIINP) secretion into culture media with radio-immunoassay (RIA). Odontoblasts expressed significantly higher basic level of type I collagen mRNA than pulp tissue or pulp fibroblasts in culture, but markedly lower level than GF and OB cells. TGF-beta 1 (10 ng/ml) had negligible effects on type I collagen mRNA expression or PINP synthesis in cultured odontoblasts and pulp tissue, and PIIINP synthesis in the odontoblasts. In PF cells, the effect of TGF-beta 1 depended on culturing conditions; a 6-fold increase in mRNA expression was observed using serum-free medium but no effect was seen in the cells cultured with 10% FBS. In contrast, GF cells serving as controls were not markedly affected by the culture conditions, with 2-3-fold increase in mRNA expression by TGF-beta 1. These experiments demonstrate that mature human odontoblasts are capable of synthesizing type III collagen protein, and that TGF-beta 1 has negligible effect on mature human odontoblast and pulp tissue collagen expression.

Baseline expression and effect of TGF-ß1 on Type I and III collagen mRNA and protein synthesis in human odontoblasts and pulp cellsIn Vitro.

Since growth factors have been suggested to regulate dentin collagen formation in response to external irritation, we investigated the effect of TGF-ß1 on proα1(I) collagen mRNA expression in cultured mature human odontoblasts and pulpal fibroblasts, as well as cultured human pulp tissue, using quantitative PCR. Cultured gingival fibroblasts (GF) and osteoblasts (OB) served as controls. Also, type I collagen synthesis in cultured odontoblasts and pulp tissue, as well as type III collagen synthesis in odontoblasts, were studied by measuring respective procollagen (PINP and PIIINP) secretion into culture media with radioimmunoassay (RIA). Odontoblasts expressed significantly higher basic level of type I collagen mRNA than pulp tissue or pulp fibroblasts in culture, but markedly lower level than GF and OB cells. TGF-ß1 (10 ng/ml) had negligible effects on type I collagen mRNA expression or PINP synthesis in cultured odontoblasts and pulp tissue, and PIIINP synthesis in the odontoblasts. In PF cells, the effect of TGF-ß1 depended on culturing conditions; a 6-fold increase in mRNA expression was observed using serum-free medium but no effect was seen in the cells cultured with 10% FBS. In contrast, GF cells serving as controls were not markedly affected by the culture conditions, with 2-3-fold increase in mRNA expression by TGF-ß1. These experiments demonstrate that mature human odontoblasts are capable of synthesizing type III collagen protein, and that TGF-ß1 has negligible effect on mature human odontoblast and pulp tissue collagen expression.

Human odontoblast culture method: the expression of collagen and matrix metalloproteinases (MMPs).

Studies on mature human odontoblasts have suffered for the lack of in vitro models. We recently introduced a human odontoblast and pulp tissue organ culture method, in which the odontoblasts are cultured in the pulp chamber after removal of the pulp tissue, and the pulp tissue can be cultured separately (Tjäderhane et al., 1998a). With this method, we have studied the effects of growth factors on the expression of collagen and extracellular matrix (ECM)-degrading enzymes, matrix metalloproteinases (MMPs), in mature human odontoblasts. TGF-beta 1 was selected because of its ability to regulate the response of the dentin-pulp complex to external irritation. The effect of TGF-beta 1 (10 ng/mL) on pro alpha 1(I) collagen mRNA was analyzed by quantitative PCR, and type I procollagen propeptide (PINP) was analyzed from conditioned culture media with RIA. Odontoblast media were also assayed for respective type III procollagen propeptide (PIIINP). TGF-beta had a negligible effect on collagen mRNA expression or protein synthesis, indicating that TGF-beta alone does not markedly induce dentin matrix formation per se in the human dentin-pulp complex (Palosaari et al., 2001). However, TGF-beta 1 seems to regulate MMP expression in mature human odontoblasts differentially. A strong down-regulation of MMP-8 (Palosaari et al., 2000), a modest down-regulation of MMP-20 (Tjäderhane et al., 2000), and considerable up-regulation of MMP-9, with no apparent effect on MMP-2 expression (Tjäderhane et al., 1998b), indicate that growth factors may affect the matrix synthesis by controlling the expression and activity of MMPs instead of collagen synthesis. The altered expression of MMPs may result in altered ECM formation, which in turn may contribute to the formation of atubular reparative dentin.

Odontoblast function seen as the response of dentinal tissue to dental caries.

Microbes are responsible for the initiation and maintaining of carious processes. They have an efficient machinery for dissolving crystalline hydroxyapatite. When initiating carious processes, microbial acid formation determines the rate of the process in enamel. When the process reaches dentin, the micro-environment changes. Dential fluid in dentin tubules is the liquid where dissolving products of apatites are destroyed. Inorganic composition of dentinal fluid, however, is not altered much during the carious process, indicating that a functional secretory domain is working to pump the dissolved calcium and phosphate ions out of the fluid. Activation of odontoblast alkaline phosphatase and dentin latent collagenases is the known cellular event during the carious process in dentin. Because the caries lesion is by definition undermining, this suggests that, in this degradation process, the extracellular compartment, crystalline hydroxyapatite is dissolved by microbial acids, and a mixture of proteinases degrades the organic matrix. The degradation products of collagen and other matrix components in dentinal fluid must be transported either through the caries lesion in the enamel to saliva or through the odontoblast to the pulp (active transport). This facilitates further processing of the degradation products intracellularly during the passage through the cell.