Bernadette Drummond

Postnatally, severe vitamin D deficiency commonly results in rickets as well as potential defects in tooth mineralization. The effects of milder deficiency on oral health outcomes later in life are still unclear. This study used micro–computed tomography (μCT), energy dispersive X‐ray analysis (EDX), and Raman spectroscopy to investigate mineral density, total density, and elemental composition of enamel and dentine in 63 exfoliated primary incisors from participants with known 25‐hydroxyvitamin D levels (25‐OHD) at birth. No differences in mineralization and chemical composition using μCT and EDX analysis were observed irrespective of 25‐OHD status. Subtle structural differences were observed via Raman spectroscopy, with more crystalline enamel observed in those with sufficient 25‐OHD at birth. Although subtle, the differences seen suggest further attention should be given to children with known milder levels of vitamin D deficiency in early life. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Vitamin D (25OHD) status during pregnancy is closely correlated with foetal and new-born 25OHD. Calcification for primary teeth begins from the fourth month of intrauterine life and from birth for permanent teeth. Dental consequences of severe 25OHD deficiency are well documented; however, consequences are less documented for milder degrees of 25OHD deficiency. This study examined the dental consequences of vitamin D deficiency/insufficiency during gestation and infancy in a cohort of 81 New Zealand children. Pregnancy and birth data for the children and their mothers and 25OHD status during gestation, birth and at five months were obtained, and dental examinations were conducted. Associations between 25OHD and enamel defects or caries experience were investigated. Of the 81 children, 55% had experienced dental caries and 64% had at least one enamel defect present. Vitamin D insufficiency (25OHD < 50 nmol/L) at all timepoints was not associated with enamel defect prevalence, but during third trimester pregnancy it was associated with an increased caries risk IRR of 3.55 (CI 1.15-10.92) by age 6. In conclusion, maternal 25OHD insufficiency during the third trimester of pregnancy was associated with greater caries experience in primary dentition. No association was found between early life 25OHD and enamel defect prevalence or severity.

Dental pulp stem cells from primary teeth cultured in serum-free conditions may have clinical use for the repair and regeneration of teeth as well as other complex tissues and organs. The aim of this study was to test the change in the stem cell markers expression/ stem cell population in human primary pulp cells at the different stages of root resorption. Caries-free human primary canines at defined stages of physiological root resorption were included (n = 9). In vitro cultures were established in xeno-free, serum-free Essential 8™ medium with human truncated vitronectin for cell attachment. An embryonic stem cell line (GENEA002) was used as a positive control. The expression of embryonic stem cell markers (Oct4, Nanog and Sox2), neural crest stem cell markers (nestin and Dlx2) and mesenchymal stem cell surface markers (CD90, CD73 and CD105) were investigated by immunocytochemistry. Mesenchymal stem cell markers CD105, CD73 and CD90 and haematopoietic markers: CD45, CD34, CD11b, CD19 and HLA-DR were quantified with flow cytometry. The early neural progenitor markers nestin and Dlx2 were detected in most serum-free cultured dental pulp stem cells, regardless of the tooth resorption stage from which they were harvested. Only isolated cells were found that expressed the embryonic stem cell transcription factors Oct4A, Nanog and Sox2, and in the late stages of resorption, no Oct4A was detected. The majority expressed the mesenchymal stem cell markers CD90, CD73 and CD105. Flow cytometry found positive signals for CD90 > 97.3%, CD73 > 99.6% and CD105 > 82.5%, with no detectable differences between resorption stages. This study identified populations of dental pulp cells in vitro with markers characteristically associated with embryonic stem cells, neural crest-derived cells and mesenchymal stem cells. Flow cytometry found CD105 expressed at lower levels than CD90 and CD73. The consistency of stem cell marker expression in cells cultured from teeth at different resorption stages suggests that pre-exfoliated primary teeth that are free of caries may provide a convenient source of multipotent stem cells for use in regenerative medicine.

This study aimed to investigate the impact of self-reported dental trauma on oral-heath-related quality of life (OHRQoL) of young adults and determine whether personality characteristics influenced how it was reported. A cross-sectional study was carried out using a sample of 435 university students. A questionnaire sought data on previous dental trauma. OHRQoL was assessed using the short-form of the oral health impact profile (OHIP-14); the outcome being one or more impacts occurring 'fairly often'/'very often'. Personality was assessed using the Positive and Negative Affect Scale (PANAS). The participation rate was 87.2%. Dental trauma experience was reported by 110 participants (25.3%), and 242 (55.6 %) indicated previous dental caries experience. Among those with dental trauma history, one or more OHIP-14 impacts was reported by 29.1% (with 21.2% among those with no history). Impact prevalence was higher among those who had previous dental caries experience (29.8%) than among those who had not (14.7%; P < 0.001). Higher PANAS negative affect scores were observed among those reporting one or more OHIP-14 impacts (P < 0.001). While dental trauma does not appear to have a negative impact on OHRQoL in young adults, past dental caries experience does. Negative emotionality influences self-reported oral health.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate treatment. Zoledronic acid (ZA) is a commonly used bisphosphonate due to its effectiveness in increasing bone density and reducing skeletal events, with evidence that it alters angiogenesis. Replacement of the mevalonate pathway using geranylgeraniol (GGOH) was studied to determine the effects of ZA on angiogenic gene expression in primary human osteoclasts. Osteoclast cultures were generated from peripheral blood mononuclear cells of three patients using the peripheral blood mononuclear cell isolation. These cells were phenotyped by phase-contrast microscopy, tartrate-resistant acid phosphatase staining, and pit assays. Primary osteoclasts were found to express a number of key angiogenic molecules at very high levels. Gene expression levels for 84 human angiogenic factors were determined using PCR arrays. Three genes with significant fold regulation (FR) in response to ZA were as follows: tumor necrosis factor (FR = +2.57, P = 0.050), CXCL9 (FR = +39.48, P = 0.028), and CXCL10 (FR = +18.52, P = 0.0009). The co-addition of geranylgeraniol with ZA resulted in the significant down-regulation of these three genes along with CCL2, TGFBR1, ENG, and CXCL1. GGOH reversed the gene changes induced by ZA and may offer a promising treatment for BRONJ.

To estimate via questionnaire within a population sample of New Zealand (NZ) children aged 6-to-10 years, the prevalence of sleep disordered breathing (SDB) and those struggling academically, and to identify individual and shared risk factors (health and demographic) for parent-reported SDB symptoms and academic difficulties. In this cross-sectional study, parents/caregivers of children were recruited through schools and social media to complete an online questionnaire covering health and demographic factors, their children's SDB symptoms (Pediatric Sleep Questionnaire; PSQ) and parental ratings of academic performance based on teacher feedback relative to expected progress in the national curriculum (well below/below/at/above) in reading, writing, and math. A total of 1205 children (53% male) aged (mean) eight years two months were included, comprising 79.4% NZ European/other and 15.0% Māori. The survey-weighted prevalence of SDB (based on the PSQ) was 17.5%. This was higher amongst those with academic difficulties rated ‘below/well below’ expected progress for reading, writing and math (estimated at 24.0%, 31.0% and 27.5% respectively), with increased odds (adjusted odds ratios) for poor progress of 1.9 (95% CI: 1.2, 3.0), 1.8 (95% CI: 1.2, 2.7) and 2.4 (95% CI: 1.6, 3.7) respectively. There were no shared risk factors common to both SDB and academic difficulties identified from multivariate analyses. The findings suggest that children with parent-reported SDB symptoms may be at high risk for poor progress in reading, writing, and math. Future research could examine whether treatment of SDB reduces barriers to learning and offsets educational risk. •The survey-weighted prevalence of ‘high risk’ for SDB was 17.5%.•These children were also at increased risk for performing ‘below’/‘well below’ that of their peers in reading, writing, and math.•There were common demographic correlates of SDB risk and academic difficulties.•No shared risk factors for SDB risk and academic difficulties were identified.

Low-wavenumber Raman spectroscopy is demonstrated for its potential to analyse mineralization abnormalities in human teeth. Four different dental samples were analysed in this study, denoted as healthy control, mild hypomineralization, enamel caries, and AI (severely degraded due to Amelogenesis imperfecta). All specimens were imaged using principal component analysis. The spectra from low- wavenumber and midwavenumber regions were simultaneously collected allowing for direct comparison between the two regions. This approach provided a method to characterize structural and chemical variation within samples. Structurally different hydroxyapatite was found to be present in the surface and bulk of the enamel. The thin outer layer of the enamel contained the most structurally ordered mineral. The obtained Raman images enabled characterization and comparison of lesion domains as well as relative hydroxyapatite abundances across all dental samples.

The etiology of dental anomalies is multifactorial; and genetic and environmental factors that affect the dental lamina have been implicated. We investigated two families of European ancestry in which males were affected by taurodontism, microdontia and dens invaginatus. In both families, males were related to each other via unaffected females. A linkage analysis was conducted in a New Zealand family, followed by exome sequencing and focused analysis of the X-chromosome. In a US family, exome sequencing of the X-chromosome was followed by Sanger sequencing to conduct segregation analyses. We identified two independent missense variants in KIF4A that segregate in affected males and female carriers. The variant in a New Zealand family (p.Asp371His) predicts the substitution of a residue in the motor domain of the protein while the one in a US family (p.Arg771Lys) predicts the substitution of a residue in the domain that interacts with Protein Regulator of Cytokinesis 1 (PRC1). We demonstrated that the gene is expressed in the developing tooth bud during development, and that the p.Arg771Lys variant influences cell migration in an in vitro assay. These data implicate missense variations in KIF4A in a pathogenic mechanism that causes taurodontism, microdontia and dens invaginatus phenotypes.

This study investigated the association between the prevalence of oral health problems (caries, gingivitis, mucosal pigmentation and enamel defects in one to 5 year-old children exposed and not exposed to environmental tobacco smoke before and/or after birth. Exposure to environmental tobacco smoke (ETS) in childhood may have significant health effects. A structured questionnaire was used to collect data on a child's current and previous illnesses, oral health behaviours, dietary habits, parental smoking behaviours and parents' dental history. The intraoral examination recorded dental caries (dmfs), enamel defects, gingival health, melanin pigmentation and soft tissue health. Stimulated saliva was collected. Total sIgA levels were quantified using indirect competitive ELISA with a SalimetricsTM kit. The 44 children (aged 15-69 months) recruited were divided into two groups: ETS and non-ETS (control). There were 22 children in each: 16 who were exposed to ETS during and after gestation were identified as the ETSB subgroup. Participants exposed to ETS were more likely to have had upper respiratory tract and middle ear infections during the neonatal period and had higher mean dmft, mean dmfs, mean percent of surfaces with demarcated opacities and mean GI than the non-ETS participants. The children exposed to ETS before and after birth had the highest occurrence of enamel opacities showed a higher risk for dental caries even though more children in this group used the recommended fluoride toothpaste (1000 ppm fluoride). Mothers who smoked either never breastfed their children or breastfed their children for less than the recommended period of 6 months. Children exposed to ETS were shown to have higher mean total sIgA (mu g/ml) than the children in the control group. Associations between ETS exposure before and after gestation and oral health, including salivary changes in young children were shown in the present study. Dental health professionals should include a question about household smoking in children's dental histories, which would allow opportunities to discuss the impact of smoking on child oral health. Longitudinal oral health studies should include a history of maternal smoking during pregnancy and afterwards.