Master’s Research Project Opportunities

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245878/

https://www.sciencedirect.com/science/article/pii/S0889540620300731?via%3Dihub

https://repository.tudelft.nl/islandora/object/uuid:9009e4af-1d2e-446c-a083-6ad07c809e06

https://pubmed.ncbi.nlm.nih.gov/38447351/

https://doi.org/10.1016/j.eclinm.2024.102550

https://repository.tudelft.nl/islandora/object/uuid%3A26bbbef4-bf75-493d-b8a1-c2da0dc132c2

The lack of availability and effectiveness of early detection measures of poor skeletal health makes patients reliant on associated factors that are easily and widely monitored. Literature shows that there is a possible association between skeletal health and dental health. From an early age, examination for dental caries is performed during the biannual dental check-ups, which makes the disease an interesting biomarker for early detection of diseases. This might enable the identification of poor skeletal health patients at an early age for whom primary and secondary preventative measures would still be effective. The purpose of this study is to overcome limitations from previous studies by evaluating the association and causal relationship between skeletal health and the severity of dental caries through an observational and genetic approach of Mendelian randomisation (MR).

The research question is: ‘To what extent is an association present between skeletal health as established by total body-less head bone mineral density and dental caries in the deciduous dentition of a paediatric population?’ The goal is to change the strategy of preventative and curative measures of both diseases from an early age through the addition of these new screening methods. This retrospective, cross-sectional study evaluates the variables in 4,378 six-year old children from the Generation R Study in Rotterdam, the Netherlands. Total body-less head bone mineral density (TBLH-BMD) and genetically predicted TBLH-BMD are indicators of skeletal health, while the decayed missing filled tooth index (dmft index) indicates the severity of dental caries divided into no caries, mild caries and severe caries. TBLH-BMD was previously measured using Dual X-ray Absorptiometry (DXA) scans, participants were previously genotyped to determine genetically predicted TBLH-BMD and the dmft index was determined from intraoral photography. Multinomial logistic regression analyses were performed to explore the observational differences of TBLH-BMD in children with different caries severity. Two-stage least squares analysis was performed using the one-sample MR framework to study the causal relationship between genetically predicted TBLH-BMD and dental caries.

According to this analysis, TBLH-BMD and mild caries have no significant relationship while there is a significant inverse relationship between TBLH-BMD and severe caries. No causal relationship of genetically predicted TBLH-BMD with dental caries could be established from the MR. This study provides evidence that it is prudent to check the skeletal health when severe caries is present. Osteoporosis at a later age might be prevented by optimizing BMD at childhood. To confirm the findings in the current study, further research could be performed with a larger sample size through combining different populations.

Bone mineral density (BMD) is the amount of mineralized content of bone per square centimeter (PMID: 20499378) in a given region of interest. Dual-energy X-ray Absorptiometry (DXA) is considered the gold standard for BMD measurements. Sufficiently low BMD leads to osteoporosis, which may lead to fractures and thus diminished quality of life (PMID: 36383282, PMID: 34165773). Peak bone mass is an important determinant of BMD and refers to the state of maximum accretion of skeletal mass, usually achieved prior to the third decade of life. Environmental factors may be modified in childhood to maximize BMD before peak bone mass is reached.  Approximately 25% of adult bone mass is accrued during the 2-year period surrounding the growth spurt (i.e., period of peak height velocity), which occurs at 12.5 ± 0.90 years old in girls and 14.1 ± 0.95 years old in boys (PMID: 10491214). By 18 years of age, 90% of peak bone mass is already achieved (PMID: 27816219). Therefore, bone mass accrual during childhood and early adulthood is an important modifiable determinant of lifelong skeletal health. Lifestyle factors also influence bone health with adequate nutrition and weight bearing physical activity having the strongest evidence of benefit (PMID: 26856587).

In children, skeletal health is assessed in DXA scans using total body less head BMD. Because DXA is affected by bone size, its use is limited in children with abnormal growth patterns, chronic disease or younger than 4 years old. Hand radiographs can be utilized to assess BMD via digital x-ray radiogrammetry. This method was shown to provide measurements similar to those obtained with DXA in children (PMID: 34029779). Radiographs are widely available, inexpensive and safe due to the relatively low radiation dose. Dental panoramic radiographs (DPRs) have been proposed as a useful tool for assessing low BMD in adults  (PMID: 23811576, PMID: 12827223, PMID: 25179243, PMID: 25480009). Many quantitative indices have been proposed to evaluate mandibular BMD. Within those, mandibular cortical thickness has been reported as having the best specificity for low BMD (PMID: 25365969). As studies have shown a positive correlation between mandibular cortical thickness and BMD of various skeletal sites, it is plausible to assume that it could be also correlated with skull BMDSK-BMD).

In children, the head has a (proportional) larger size and different growth pattern compared to the whole body (PMID: 16004538). Hence, the head ROI is excluded from the BMD assessment in pediatric populations. SK-BMD has been shown to have weaker associations with anthropometric, body composition, and lifestyle factors than other skeletal sites (PMID: 35398588). As such, SK-BMD has emerged as a relevant parameter for bone research. It has high heritability and is considerably less affected by environmental influences (PMID: 37402774). Interestingly, in spite of less mechanical loading, calvarial osteocytes have been shown to maintain bone mass. Cranial bone mass does not decline abruptly after menopause, bed rest, or spaceflight (PMID: 36225206). On account of those unique characteristics, analyzing SK-BMD provides an opportunity to elucidate an individual’s genetic potential for bone mass accrual, peak bone mass, and growth (PMID: 22792070). Previous genome-wide association studies (GWAS) in children have identified genetic variants influencing SKBMD and other skeletal sites with site-specific effects. This suggests differences in gene regulation across skeletal sites (PMID: 24945404, doi: https://doi.org/10.1101/2021.11.01.21265592).

Altogether, these genetic discoveries allow the study of the association between SK-BMD and mandibular cortical thickness in an unconfounded manner. The recallby-genotype (RbG) approach focuses on the extremes of a polygenic risk score (PRS) distribution allowing to stablish an unconfounded association between two traits. PRS are representations of the summarized effects of multiple independent genetic variants affecting the individual’s phenotype (PMID: 32709988). Due to the random allele allocation at conception, the confounders across groups of the PRS are assumed randomized as well (PMID: 29459775). Thus, the RbG design is less susceptible to confounding and reverse causality. 

Introduction: Tooth agenesis is one of the most common human anomalies, with the third molar (M3) being most frequently affected. No Dutch epidemiological data is available and less is known about possible predictors of M3 agenesis. The research question is: What is the prevalence of M3 agenesis and what are possible predictors associated with this anomaly? This will provide Dutch epidemiological findings and may contribute to a better understanding of the etiology.

Materials and methods: This study was embedded in the Generation R Study, a Dutch populationbased, prospective cohort study. Orthopantomographs (OPTs) were taken to ascertain M3 agenesis and questionnaires were used to collect data about maternal smoking and medication use, children’s ethnic background and other population characteristics. A McNemar test and a binary logistic regression analysis with a forward selection model were used for statistical analyses and p-values of 0.05 and 0.1 were chosen as significant, respectively.

Results: In total, the population consisted of 4,713 participants with data on M3 agenesis. The prevalence of M3 agenesis was 19.7%. Prevalence did not significantly differ between maxilla and mandible (p = .709). A Western ethnicity (p = .007) and maternal iron supplement use (p = .074) were associated with a significant higher odds of M3 agenesis, while antimycotic use (p = .058) was associated with a lower odds. Sex, maternal smoking status and other maternal used medication groups were found to have no significant influence on the odds of M3 agenesis.

Conclusion: These results show the higher presence of M3 agenesis within the Western population and the association between specific maternal used medication groups and M3 agenesis. No association was shown among the other variables. This provide clinicians useful information for patient counseling and diagnostics. Due to lack of supporting literature, further studying the association between maternal medication use and M3 agenesis is recommended.

Introduction: Caries is the most common chronic disease worldwide. Because the widespread prevalence of caries is mainly caused by individual behaviour, it is paramount to research caries risk factors components related to oral health behaviours to overcome a growing health burden. Considering parents lay the foundation towards their children’s attitude about food makes research about the association between parental feeding practices and dental caries important. Since there is a lack of study whether there is an association between parental feeding practices and dental caries it is important to study this association. The primary research question is: “What is the association between parental feeding practices and dental caries in the deciduous dentition?”

Materials and methods: The present longitudinal observational study is embedded in Generation R, a large population-based cohort study in Rotterdam. Parental feeding practices were assessed by a modified version of the validated CFQ questionnaire around 4 years of age. Dental caries was determined from a series of digital intra-oral photographic records using dmft around 6 years of age. Information about the confounders (age, sex, ethnic background and socio-economic status, toothbrushing frequency and regular dental check-ups) were assessed via questionnaires during enrolment in the study and around 5 years of age. For statistical analysis multinomial logistic regression were used.

Results: In total, the population consisted of 3417 participants with data available on dmft and CFQ. The prevalence of dental caries in the study population was 25.5%. Monitoring, restrictive and pressuring feeding practices were significantly associated with severe caries. The only indicator associated with mild caries was the monitoring feeding practice. After making adjustments for the possible confounding variables, the monitoring feeding practice remained significantly negatively associated with both mild and severe dental caries, while the other initial significant findings about associating restrictive and pressuring feeding practices with caries could be accounted for by confounding variables. The protective effect on caries from monitoring feeding practices on caries is observed between complete and almost complete monitoring feeding practices.

Conclusion: Always applying monitoring feeding practices appears to be protective against dental caries, while restrictive and pressuring feeding practices lose their positive association with dental caries after correction for confounding variables. Given the lack of existing literature on the association between the CFQ and dmft it is advisable to further research this topic in order to be able to provide better indications of how caries development in children could be prevented through focusing on adapting changing parental feeding practices.

Objective: The aim of this study is to assess the association between asthma and asthma medication in young adolescents and the occurrence of caries, assessed on all permanent teeth, at the age of thirteen.

Methods: In our population-based study 2357 participants were included. This project is embedded in the Generation R study, a prospective cohort study that followed pregnant women and their offspring from birth until young adulthood. The asthma group was formed based on questionnaires completed by the parents. Dental caries was scored on intraoral photographs by using the decayed, missing and filled teeth (DMFT) index. The following variables were identified as confounders: child’s age, sex at birth, family socio-economic status (SES), ethnic background and oral hygiene habits. We applied the hurdle regression models to study the association between asthma and dental caries. A negative binomial distribution is used in the hurdle model.

Results: The results of the negative binomial hurdle models show that, after adjustment for confounding variables, asthma diagnosis or medication use is not significantly associated with dental caries. However, we did see an effect of sex, age, ethnicity, education level of the mother and frequency of tooth brushing on the prevalence of dental caries.

Conclusion: The results of this study show that nor asthma nor the use of asthma medications is associated with an increased risk of having dental caries in a generally healthy population.

Background and objectives: Previous studies have shown that oral health in adolescents has deteriorated in recent years. Over the past decades there is increasing evidence that dietary habits of adolescents have been changing rapidly. It has been suggested that the changes in dietary habits are responsible for the deterioration of oral health outcomes since several studies have shown that dietary habits are associated with eating more unhealthy cariogenic foods. The purpose of the study was to investigate the association between dietary habits and dental caries among young adolescents, and to identify the role of oral hygiene and SES. The following research question has been formulated: To what extent are dietary habits associated with dental caries among 13 year old adolescents in the Netherlands and how is this association influenced by oral hygiene and SES?

Methods: This study included 4085 thirteen-year-olds from the Generation R study, a prospective population-based birth cohort study. Dental caries data was collected via intraoral photographs and the application of the decayed, missing, and filled teeth (DMFT) index for permanent dentition. Data on dietary habits, oral health behavior and SES were collected via a questionnaires. A multinomial regression analysis was performed to analyze the association between dietary habits and dental caries, expressed in odd ratio’s (OR’s) with 95% confidence intervals (CI’s). The level of statistical significance was set at p < 0.05. Three different regression models (A,B and C) were constructed per dietary habit. The regression models were adjust for gender, age, oral health behavior and socioeconomic variables. Young adolescents were categorized into three groups based on their dental caries experience (DMFT = 0 versus DMFT = 1-3 or DMFT > 3).

Results: All dietary variables were significantly associated with severe caries in model A. After adjusting for oral health behavior and SES variables, only vegetable consumption remained inversed significantly associated with mild and severe caries. For model B all used dietary variables had no association for both mild and severe caries. The variable ‘’eat at fastfood restaurant’’ in model C was significantly associated with severe caries, but this association disappeared when SES indicators were taken into account.

Discussion/conclusion: The role of SES is very important for the associations between dental caries and dietary habits. In all models, the observed significant effect in model 1 (basic model adjust for age, sex and dietary habits) disappeared in model 3 (most complete model, adjust for oral health and SES variables), which can be explained by strong relation between dietary habits and SES. These results were not as expected because from the perspective of caries etiology, lower plaque pH values and slower increase in pH after exposure to sugar will cause dental caries. This unexpected results can be caused due to the method of measuring dietary data and the categorization. The results from model 1,2 and 3 showed clearly that the association to dental caries is attenuated after adjusting for oral health behavior and SES.