Vitamin A enhanced periosteal osteoclastogenesis is associated with increased number of tissue-derived macrophages/osteoclast progenitors.

A deleterious effect of elevated levels of vitamin A on bone health has been reported in clinical studies. Mechanistic studies in rodents have shown that numbers of periosteal osteoclasts are increased, while endocortical osteoclasts are simultaneously decreased by vitamin A treatment. The present study investigated the in vitro and in vivo effect of all-trans retinoic acid (ATRA), the active metabolite of vitamin A, on periosteal osteoclast progenitors. Mouse calvarial bone cells were cultured in media containing ATRA, with or without the osteoclastogenic cytokine receptor activator of nuclear factor kappa B-ligand (RANKL), on plastic dishes or bone discs. Whereas ATRA did not stimulate osteoclast formation alone, the compound robustly potentiated the formation of RANKL-induced bone resorbing osteoclasts. This effect was due to stimulation by ATRA (half-maximal stimulation ∼3 nM) on the numbers of macrophages/osteoclast progenitors in the bone cell cultures, as assessed by mRNA and protein expression of several macrophage and osteoclast progenitor cell markers, such as macrophage colony-stimulating factor receptor, receptor activator of nuclear factor kappa B, F4/80, and CD11b, as well as by flow cytometry (FACS) analysis of CD11b+/F480+/Gr1- cells. The stimulation of macrophage numbers in the periosteal cell cultures was not mediated by increased macrophage colony-stimulating factor or interleukin-34. In contrast, ATRA did not enhance macrophages in bone marrow cell cultures. Importantly, ATRA treatment upregulated the mRNA expression of several macrophage-related genes in the periosteum of tibia in adult mice. These observations demonstrate a novel mechanism by which vitamin A enhances osteoclast formation specifically on periosteal surfaces.

The novel cytotoxic polybisphosphonate osteodex decreases bone resorption by enhancing cell death of mature osteoclasts without affecting osteoclastogenesis of RANKL-stimulated mouse bone marrow macrophages.

It has previously been demonstrated that the polybisphosphonate osteodex (ODX) inhibits bone resorption in organ-cultured mouse calvarial bone. In this study, we further investigate the effects by ODX on osteoclast differentiation, formation, and function in several different bone organ and cell cultures. Zoledronic acid (ZOL) was used for comparison. In retinoid-stimulated mouse calvarial organ cultures, ODX and ZOL significantly reduced the numbers of periosteal osteoclasts without affecting Tnfsf11 or Tnfrsf11b mRNA expression. ODX and ZOL also drastically reduced the numbers of osteoclasts in cell cultures isolated from the calvarial bone and in vitamin D3-stimulated mouse crude bone marrow cell cultures. These data suggest that ODX can inhibit osteoclast formation by inhibiting the differentiation of osteoclast progenitor cells or by directly targeting mature osteoclasts. We therefore assessed if osteoclast formation in purified bone marrow macrophage cultures stimulated by RANKL was inhibited by ODX and ZOL and found that the initial formation of mature osteoclasts was not affected, but that the bisphosphonates enhanced cell death of mature osteoclasts. In agreement with these findings, ODX and ZOL did not affect the mRNA expression of the osteoclastic genes Acp5 and Ctsk and the osteoclastogenic transcription factor Nfatc1. When bone marrow macrophages were incubated on bone slices, ODX and ZOL inhibited RANKL-stimulated bone resorption. In conclusion, ODX does not inhibit osteoclast formation but inhibits osteoclastic bone resorption by decreasing osteoclast numbers through enhanced cell death of mature osteoclasts.

Osteoprotective effect by interleukin-4 (IL-4) on lipoprotein-induced periodontitis.

Lipoproteins are immunostimulatory bacterial components suggested to participate in inflammation-induced bone loss in periodontal disease through stimulation of osteoclast differentiation. Toll-like receptor 2 activation by Pam2CSK4 (PAM2), known to mimic bacterial lipoproteins, was previously shown to enhance periodontal bone resorption in mice. The anti-inflammatory cytokine interleukin-4 (IL-4) is a known inhibitor of RANKL-induced bone resorption in vitro. Here, we have investigated whether IL-4 could decrease PAM2-induced periodontal bone loss and osteoclastogenesis in vivo. In a model of periodontitis induced by gingival injections of PAM2 in mice, concomitant injections of IL-4 reduced bone loss. Histologically, IL-4 reduced the recruitment of inflammatory cells and the formation of TRAP+ osteoclasts stimulated by PAM2. Mouse bone marrow macrophages (BMMs) and neonatal calvarial osteoblasts were used to assess the effect of IL-4 on PAM2-induced osteoclastogenesis in vitro. In RANKL-primed BMMs stimulated by PAM2 Nfatc1, Ctsk, and Acp5 gene expression was up-regulated and resulted in robust formation of TRAP+ multinucleated osteoclasts, effects which were impaired by IL-4. These effects were mediated by impairment in PAM2-induced c-fos expression. In primary calvarial osteoblast cultures, IL-4 decreased PAM2-induced Tnfsf11 (encoding RANKL) mRNA and enhanced Tnfrsf11b (encoding OPG) expression. Our data demonstrate that the osteoprotective effect by IL-4 on lipoprotein-induced periodontal disease occurs through the inhibition of osteoclastogenesis by three mechanisms, one by acting directly on osteoclast progenitors, another by acting indirectly through decreasing the expression of osteoclast-regulating cytokines in osteoblasts and a third by decreasing inflammation.

Effects of fixed retainers on gingival recession - a 10-year retrospective study.

OBJECTIVE: The aetiology of gingival recessions is not fully understood, and no evidence has yet emerged of a single predisposing factor that instigates this apical shift of the gingival margin. Nonetheless, both fixed retainers and orthodontic treatment have been cited as potential risk factors. The aim of this study was to assess the effects of orthodontic treatment and orthodontic fixed retainers on gingival recessions. SUBJECTS AND METHODS: In total, 105 patients at the Department of Orthodontics at the University of Gothenburg who had undergone orthodontic treatment between 1995 - 2003 were included in this study. Intraoral photographs of the anterior segment and study casts acquired at baseline (pre-treatment), post-treatment and at the 10-year follow-up were used as recorded measurements of gingival recession and orthodontic treatment. At the 10-year follow-up, the patients were divided into two groups based on: long-term (10 years) presence of a fixed retainer [orthodontic treatment and retainer (OR) group; N = 76]; and short-term (<5 years) presence of a fixed retainer [orthodontic treatment (O) group; N = 57]. These groups were compared to a control group (C) of untreated subjects (N = 29). RESULTS: In the anterior segment, gingival recessions were not present at baseline and post-treatment between the two orthodontically treated groups. At the 10-year follow-up, there was no statistically significant difference between the two orthodontically treated groups and the controls. CONCLUSIONS: Orthodontic treatment per se does not increase the risk for gingival recessions, nor does the use of fixed retainers following orthodontic treatment.

Dentoskeletal and soft tissue changes after treatment of crowding with premolar extractions: a 50-year follow-up.

BACKGROUND: The long-term effects on dentofacial morphology of interceptive treatment with premolar extractions, in the absence of subsequent orthodontic treatment, have not been fully explored. OBJECTIVE: The aim was to investigate the effects of premolar extractions (without subsequent orthodontic treatment) on the dentoskeletal and soft tissue profile of patients aged between 12 and 62 years with Class I malocclusion with severe crowding, as compared to untreated controls. MATERIALS AND METHODS: The Extraction group (N = 30 with Class I crowding malocclusion) had their first premolars removed in early adolescence without subsequent orthodontic treatment. The Control group included 30 untreated subjects with Class I normal occlusion. Cephalograms were taken at 12 (T1), 15 (T2), 30 (T3), and 62 (T4) years of age. A superimposition-based cephalometric method was used to assess the dentoskeletal and soft tissue changes. RESULTS: There were no significant differences between the Extraction and Control groups in terms of skeletal sagittal relation, incisor inclination, and protrusion, or most of the soft tissue parameters throughout the observation period. However, significant differences were observed between the groups with respect to the vertical relations in T2-T3, such that the Extraction group showed more-pronounced decreases in the ML/NSL, ML/NL, and Gonial angles and more-pronounced increases in facial heights. CONCLUSIONS AND IMPLICATIONS: Treatment for subjects with Class I malocclusion with severe crowding by the extraction of four premolars, without subsequent orthodontic treatment, does not affect the long-term dentoskeletal and soft tissue profile, as compared to an untreated Control group. The degree of crowding, rather than changes in dentofacial morphology, is crucial in deciding on extraction therapy.

Effect of high-fluoride toothpaste and mouth rinse on the prevention of demineralized lesions during orthodontic treatment: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of high-fluoride mouth rinse and high-fluoride toothpaste on the development of demineralized lesions (DLs) during orthodontic treatment. TRIAL DESIGN: Three-armed parallel-group randomized controlled trial. METHODS: The trial was performed with 270 adolescent orthodontic patients. Randomization was performed in blocks of 30, enrolling the patients into one of the following groups: the fluoride mouth rinse (FMR) group receiving 0.2% sodium fluoride (NaF) mouth rinse plus 1450 ppm fluoride (F) toothpaste; high-fluoride toothpaste (HFT) group receiving 5000 ppm F toothpaste; and the Control (CTR) group receiving 1450 ppm F toothpaste. Inclusion criteria were patients scheduled for treatment in both arches with fixed appliances and age between 12 and 20 years. The primary outcome variable was the proportion of participants with at least one new demineralized lesion as assessed on digital photos taken before and after treatment, analysed by a blinded clinician. The analysis included all teeth or teeth in the aesthetic zone, i.e. all central incisors, lateral incisors, and canines. A random sample of 30 participants was assessed to check intra- and inter-reliability. For pairwise comparison between groups, Fisher's non-parametric permutation test was used for continuous variables. Blinding was employed during the caries registration and data analysis. RECRUITMENT: October 2010 to December 2012. RESULTS: In total, 270 patients were randomized, of which 22 were excluded during treatment. Therefore, 248 participants were included in the study. The number of patients with an increase of ≥1 DL, including only central- and lateral incisors and canines, during orthodontic treatment, was significantly lower in the HFT group, 51/85 60%, compared to the CTR group, 64/82 78%, RR 0.77 (CI 0.62; 0.95), P = .01 and in the FMR group, 47/81 58%, compared to the CTR group, RR 0.74 (CI 0.60; 0.92), P < .01. CONCLUSIONS: To prevent demineralized lesions in the aesthetic zone, high-fluoride mouth rinse and high-fluoride toothpaste may be recommended. LIMITATIONS: The protocol was not registered, and the present study did not use a double-blinded design.

Early extractions of premolars reduce age-related crowding of lower incisors: 50 years of follow-up.

OBJECTIVES: To study the effects of extraction of four premolars, without subsequent orthodontic treatment, on the crowding of lower incisors in subjects between early adolescence and late adulthood, as compared to untreated subjects. MATERIALS AND METHODS: A total of 45 subjects were included in this study. The extraction group comprised 24 subjects who had all the first premolars removed at a mean age of 11.5 years, to relieve crowding in a class I malocclusion without subsequent orthodontic treatment. The control group had 21 untreated subjects, having a normal occlusion at a mean age of 13.0 years. The participants were documented with dental casts and cephalograms at mean ages of 11.4 and 13.0 years, for the two groups respectively (T1), and at mean ages of 30.9 years (T2) and 61.7 years (T3). Changes in lower incisor crowding were described as changes in "irregularity" and "space deficiency." RESULTS: The extraction group showed no changes in the irregularity of the lower incisors and significant improvement of the space deficiency of the lower teeth into late adulthood. While in the control group, both irregularity of the lower incisors and space deficiency of the lower teeth increased significantly into late adulthood. CONCLUSION: Lower incisor alignment remains mainly unchanged into late adulthood in subjects who have all their first premolars removed in childhood, as the only treatment to relieve teeth crowding. CLINICAL RELEVANCE: Severe crowding in a class I occlusion can be solved solely with premolar extraction, allowing for spontaneous adjustments with more stable incisor alignment up to late adulthood.

Effect of a mouth rinse and a high-fluoride toothpaste on caries incidence in orthodontic patients: A randomized controlled trial.

INTRODUCTION: The objective was to evaluate the effect of a fluoride mouth rinse and a high-fluoride toothpaste on caries incidence in patients undergoing orthodontic treatment with fixed appliances. METHODS: In this 3-armed, parallel-group, randomized controlled trial, patients referred to the Specialist Clinic of Orthodontics, Mölndal, Sweden, were randomly allocated to 1 of the 3 groups. (1) Fluoride mouth rinse (FMR) group: 0.2 % sodium fluoride (NaF) mouth rinse plus 1450 ppm fluoride (F) toothpaste; (2) High-fluoride tootpaste (HFT) group: 5000 ppm F toothpaste; and (3) Control (CTR) group: 1450 ppm F toothpaste. The generation of a randomization sequence was performed in blocks of 30. Inclusion criteria included patients scheduled for treatment with fixed appliances in the maxillary and mandibular arch aged 12-20 years. The primary outcome variable was the change in Decayed Initial Filled Surfaces (ΔDiFS) based on radiographs taken before and after the treatment. For statistical comparisons between groups, the Kruskal-Wallis test were used for continuous variables, whereas the Mann-Whitney U-test was used for pairwise group comparisons. Furthermore, the risk ratio (RR) and 95% confidence interval (CI) based on clinically relevant cutoffs (DiFS ≥2) were calculated to compare the increase of caries during orthodontic treatment between 2 groups. The Cochran-Mantel-Haenszel method was used to adjust RR for baseline values. Blinding was employed during the caries registration and the data analysis. RESULTS: In total, 270 participants were randomized, with 15 patients dropping out, such that 255 patients were included in the statistical analyses. Recruitment was from October 2010 to December 2012. An increase in DiFS (≥1 DiFS) during treatment was observed in 48.3% of the FMR group, 42.0% of the HFT group, and 35.6% of the CTR group. There was no significant difference between the groups regarding increased DiFS (P = 0.17). The risk of increase in DiFS ≥2 during orthodontic treatment was 31.0% in the FMR group, 25.9% in the HFT group, and 18.4% in the CTR group. The RR for an increase of ≥2 DiFS during orthodontic treatment was 1.38 (95% CI, 0.81-2.34; P = 0.23) for FMR vs CTR, 1.21 (95% CI, 0.70-2.10; P = 0.51) for HFT vs CTR, and 0.93 (95% CI, 0.57-1.49; P = 0.76) for HFT vs FMR. CONCLUSIONS: In patients who demonstrate a low prevalence of caries and are undergoing orthodontic treatment, daily use of high-fluoride toothpaste or fluoride mouth rinse in combination with regular toothpaste does not appear to significantly alter the caries incidence compared with the use of regular toothpaste. TRIAL REGISTRATION: The trial was registered in the FoU i Sverige research database (http://www.fou.nu/is/sverige), with registration no. 236251. PROTOCOL: The protocol was not published before trial commencement. FUNDING: Local Research and Development Board for Gothenburg and South Bohuslän (grant no. 768531); and The Swedish Patent Revenue Fund (grant number EKF-780/19).

Craniofacial changes from 13 to 62 years of age.

BACKGROUND: In long-term studies of orthodontic, orthognathic, and prosthodontic treatments, control subjects are needed for comparison. OBJECTIVES: To study the craniofacial (skeletal, soft tissue, and dental) changes that occur in untreated subjects with normal occlusion between 13 and 62 years of age. MATERIALS/METHODS: Thirty subjects with a Class I normal occlusion and harmonious facial profile were studied. X-ray examinations were performed at 13 (T1), 16 (T2), 31 (T3), and 62 (T4) years of age, and data were obtained from cephalograms. In total, 53 angular and linear parameters were measured using superimposition-based and conventional cephalometric methods to describe the craniofacial changes. RESULTS: The jaws showed significant anterior growth from T1 to T2, and significant retrognathism from T3 to T4. The anterior face height and jaw dimensions increased significantly until T3. Significant posterior rotation of the mandible and opening of the vertical jaw relation, in addition to significant retroclination of the incisors and straightening of the facial profile, were found from T3 to T4. LIMITATIONS: Given the small sample size at T4, it was not possible to analyse the gender dimension. CONCLUSIONS/IMPLICATIONS: Craniofacial changes continue up to the sixth decade of life. These changes are consistent, albeit to a lesser extent, with the adolescent growth patterns for most of the studied parameters, with the exceptions of incisor inclination, sagittal jaw position, vertical jaw relation and inclination, and posterior face height.

Immunoglobulin G complexes without sialic acids enhance osteoclastogenesis but do not affect arthritis-mediated bone loss.

Immunoglobulin G (IgG) is important in clearance and recognition of previously presented antigens and after activation, IgGs can interact with the Fc gamma receptors (FcγRs) on haematopoietic cells, including bone-resorbing osteoclasts. The pathogenicity of IgG, that is the ability to elicit stimulatory effects via FcγRs, can be modulated by attachment of sugar moieties, including sialic acids. Human IgGs and autoantibodies are associated with bone loss in autoimmune disease. However, the impact of polyclonal murine IgG via FcγRs on bone loss is poorly understood. Here, we investigate if heat-aggregated activated murine polyclonal IgG complexes have any direct effects on murine osteoclasts and if they modulate arthritis-mediated bone loss. Using cell cultures of murine osteoclasts, we show that IgG complexes without sialic acids (de-IgG complexes) enhance receptor activator of nuclear factor kappa-Β ligand (RANKL)-stimulated osteoclastogenesis, an effect associated with increased FcγRIII expression. Using an in vivo model of arthritis-mediated bone loss, where IgG complexes were injected into arthritic knees, no effect on the severity of arthritis or the degree of arthritis-mediated bone loss was detected. Interestingly, injection of de-IgG complexes into non-arthritic knees increased osteoclast formation and enhanced bone erosions. Our findings show that activated de-IgG complexes have no additive effect on arthritis-mediated bone loss. However, de-IgG complexes potentiate murine osteoclastogenesis and enhance local bone erosion in non-arthritic bones, further confirming the link between the adaptive immune system and bone.

Choice of radiography in orthodontic treatment on children and adolescents: A questionnaire-based study performed in Sweden.

The aim was to investigate the objective and choice of different radiographic examinations used in orthodontic treatment of children and adolescents, using a web-based questionnaire directed toward specialists in orthodontics. The questionnaire was distributed to 255 orthodontists in Sweden. In total, 142 responses were received, and 11 specialists were interviewed. Questions were related to the use of radiography during different treatment stages; modifications to the treatment regimen owing to radiographic findings; and the use of and/or need for guidelines in radiography. Radiographic examinations were performed in all treatment stages and mainly during treatment planning. Panoramic radiographs were always or often used by the respondents (99%), less frequently used were lateral radiographs (66%) and intra-oral radiographs of the incisor regions (69%). Cone beam computed tomography (CBCT) was sparsely employed. A majority of the respondents considered that radiographic findings often or occasionally affected the treatment. Local- or clinic-specific guidelines were used by 85% of respondents. The need for national guidelines was considered low. The frequent use of panoramic radiography together with application of local guidelines, may indicate that radiographic selection criteria are not individualised. National guidelines might facilitate updates on radiographic techniques, and on radiation doses and risks in young patients.

Dental age in children with impacted maxillary canines.

OBJECTIVE: The aim of this study was to evaluate if delayed dental development is a cause of postponed care for patients with impacted maxillary canine (IMC). MATERIALS AND METHODS: This case-control study was based on 403,355 children and adolescents in Region Västra Götaland, Sweden. The subjects, who were in the age range of 9-16 years during the period of 2011-2013, underwent surgical exposure or removal of a maxillary canine. Demirjian's dental age assessment was carried out on panoramic radiographs. RESULTS: In total, 1028 patients, 514 with IMC and 514 age- and gender-matched controls, were enrolled. The patients with IMC exhibited a dental development delay of 0.2 years compared to the control group. In the impaction sub-groups, the female patients, patients in the chronological age group of 12-13 years, and patients with palatally positioned IMC had a significantly lower dental age than their paired-control subjects. CONCLUSIONS: Overall, the difference in dental age between patients with or without IMC is significant but small, and as such is likely of minor clinical relevance. Therefore, the timing of preventive care and treatment for patients with IMC should be the same as that for patients with normally erupting canines.

Evidence-based practice in child and adolescent mental health services - The challenge of implementing national guidelines for treatment of depression and anxiety.

BACKGROUND: Mental health problems are one of the most pressing public health concerns of our time. Sweden has seen a sharp increase in mental disorders among children and youth during the last decade. The evidence base for treatment of psychiatric conditions has developed strongly. Clinical practice guidelines aim to compile such evidence and support healthcare professionals in evidence-based clinical decision-making. In Sweden, the national guidelines for the treatment of depression and anxiety disorders in children and adolescents were launched in 2010. The aim of this study was two folded, (i) to explore to what extent these guidelines were known and adhered to by health professionals in Child and Adolescent Mental Health Services and (ii) to investigate factors influencing implementation of the guidelines informed by the Consolidated Framework for Implementation Research. METHODS: A qualitative approach was used, and data were collected through interviews with 18 health professionals in Child Mental Health Services in Sweden and a combination of conventional and directed content analyses was used. The Consolidated Framework for Implementation Research guided and structured data collection and analysis. RESULTS: The guidelines were largely unknown by health professionals in Child Mental Health Services in all the clinics investigated. Adherence to guideline recommendations was reported as very low. Barriers to implementation were found in relation to the characteristics of the intervention, outer setting, inner setting and characteristics of the individuals involved. CONCLUSIONS: The government initiative to develop and disseminate the guidelines seems to have made very little impact on health professionals' clinical practice. The guidelines were poorly aligned with the health professionals' knowledge and beliefs about effective mental health services for children and youth with depression and anxiety disorders. Suggestions for future efforts to improve the development and implementation of guidelines in Child Mental Health Services settings are given.

Lateral and Frontal Cephalometric Measurements in a Cohort With Saethre-Chotzen Syndrome.

OBJECTIVE: Descriptions of the craniofacial morphology in Saethre-Chotzen syndrome (SCS) are primarily based on case reports or visual assessments of affected families. The aim of this study was to compare cephalometric measurements of the craniofacial skeleton in a cohort of individuals with SCS and age- and sex-matched individuals without craniofacial anomalies. DESIGN: Retrospective case series. PATIENTS: Eight girls and 4 boys with SCS (age range, 7.0-19.2 years). METHODS: Cephalometric measurements were performed using lateral and frontal cephalograms. RESULTS: Most of the individuals with Saethre-Chotzen syndrome exhibited lower values for SNA, SNB, s-n and s-ar, while their NSL/NL, NSL/ML, NL/ML, and n-s-ba values were higher than the respective mean reference values for healthy individuals. In comparison with age- and sex-matched individuals without craniofacial anomalies, the individuals with SCS showed higher values for the maxillary and mandibular angular measurements, as well as for the menton midline angle. CONCLUSIONS: This sample of 12 unrelated individuals with SCS is the largest collected to date for cephalometric measurements. We found that the syndrome is associated with bimaxillary retrognathism, posterior maxillary and mandibular inclination, neutral sagittal relation as well as a tendency toward an open vertical skeletal relation, a short and flattened skull base, and facial asymmetry, as compared to individuals without the syndrome.

Brachial plexus block with ultrasound guidance for upper-limb trauma surgery in children: a retrospective cohort study of 565 cases.

BACKGROUND: Upper-limb trauma is a common indication for surgery in children, and general anaesthesia remains the method of choice for these procedures, even though suitable techniques of brachial plexus block are available and fast provision of regional anaesthesia offers a number of distinct advantages. METHODS: A retrospective analysis was performed of the data of a large cohort of children undergoing ultrasound-guided brachial plexus blocks during a 4-yr period at a major trauma centre with a catchment area of 3.5 million. A total of 565 cases were sourced from two independently operating patient documentation systems. Patient data were stratified into age groups with block success as the primary outcome parameter. The influence of age on the incidence of block failure was assessed with logistic regression. RESULTS: The block failure rate was 5.1%, starting at 1.2% in the youngest (0-3 yr), then continuously increasing up to 12.5% in the oldest (15-18 yr) but also smallest group. Age emerged as an independent predictor of block failure with an odds ratio of 1.115 and a 95% confidence interval of 1.014-1.226 (P=0.025). No complications were observed. CONCLUSIONS: In a cohort of children receiving real-world care, with regional blocks performed by a range of anaesthetists with different skill levels, a success rate of 94.9% for upper-limb blocks in children under various levels of sedation was observed. Upper-limb blocks can be performed with high probability of success and an excellent margin of safety; this particularly applies to small children. CLINICAL TRIAL REGISTRATION: NCT03842423.

Validation of caries risk assessment methods in orthodontic patients.

INTRODUCTION: Dental caries is an undesirable side effect of orthodontic treatment with fixed appliances. Caries lesions can result in long-term esthetic disturbance, costly interventions, and even interrupted treatment. Therefore, it is crucial to assess accurately both a patient's caries risk before treatment and their suitability for orthodontic treatment. This study aimed to evaluate the validity of 5 caries risk assessment methods for predicting caries outcome during orthodontic treatment: Cariogram, Caries Management by Risk Assessment (CAMBRA), R2, decayed filled teeth (DFT), and decayed initial filled surfaces (DiFS). METHODS: A prospective longitudinal clinical study of 270 adolescents who were referred to the Specialist Clinic for Orthodontics, Mölndal Hospital, Sweden for treatment with fixed orthodontic appliances. The following data were collected before treatment: plaque index, radiographs to determine caries prevalence (DFT, DiFS), photographs to determine white-spot lesions, saliva samples (Streptococcus mutans and Lactobacilli), and responses to a questionnaire (regarding diet and oral hygiene). The variables were compiled to assess caries risk according to Cariogram, CAMBRA, and R2. Radiographs were also taken posttreatment to assess caries incidence. The caries outcomes after treatment were analyzed and compared with the caries risk, assessed by the caries risk assessment methods at baseline. RESULTS: DiFS proved to be the most reliable method for predicting caries during orthodontic treatment, presenting the highest area under the receiver operating characteristic curve for both manifest caries (0.77) and initial caries (0.71). CONCLUSIONS: The DiFS prevalence index was demonstrated to be useful in identifying patients who are at risk for developing manifest and initial caries during orthodontic treatment.

Prevalence of impacted maxillary canines-an epidemiological study in a region with systematically implemented interceptive treatment.

BACKGROUND: In dentistry, epidemiological studies are important for establishing high-quality care for the individual patient as well as for socio-economic reasons. OBJECTIVE: The aim of this epidemiological study was to evaluate the prevalence of impacted maxillary canines in a geographical region in which interceptive treatment is implemented systematically. Furthermore, the aim was to study the age and gender of the patients, and the location and surgical technique used for the impacted maxillary canine. METHOD: The study was based on 54 716 adolescents in the Region Västra Götaland, Sweden who were born in the period 1996-98. All patients in the three cohorts who had impacted maxillary canines treated with surgical exposure or surgical removal were identified in the dental record system used in the region. RESULTS: The prevalence of impacted maxillary canines when interceptive treatment was systematically implemented was 1.1% (N = 601). Overall, the cohorts of patients with impacted canines comprised 65% girls and 35% boys. Most of the canines were palatally impacted and the most common surgical technique was closed exposure. CONCLUSION: The prevalence of impacted maxillary canines in a geographical area in which interceptive treatment is systematically implemented is lower than that reported previously. The distributions of impacted canines with respect to gender and location are in accordance with those reported previously in similar studies.

Effects of orthodontic treatment and different fluoride regimens on numbers of cariogenic bacteria and caries risk: a randomized controlled trial.

Background: Caries is an undesirable side-effect of treatment with fixed orthodontic appliances. Therefore, it is crucial to understand how orthodontic treatment and different fluoride regimens affect caries risk and individual risk factors. Objective: To evaluate the effects of orthodontic treatment and different fluoride regimens on caries risk and caries risk factors, including cariogenic bacteria. Trial design: Three-armed, parallel group, randomized, controlled trial. Methods: Patients referred to the Specialist Clinic of Orthodontics, Mölndal Hospital, Sweden, were distributed randomly into the following groups: group I (Control group), 1450 ppm fluoride (F) toothpaste; group II, 1450 ppm F toothpaste plus 0.2 per cent sodium fluoride (NaF) mouth rinse; and group III, 5000 ppm F toothpaste. The inclusion criteria were: age 12-20 years; and bimaxillary treatment with fixed appliances. The primary outcome variables were: caries risk; and the numbers of cariogenic bacteria. Radiographs were taken before treatment to determine the caries status. Data were collected before treatment and after 1 year with a fixed appliance. The variables were compiled into a Cariogram to assess the caries risk. Comparisons were made over time within and between the groups. The generation of randomization sequence was performed in blocks of 30. Blinding was employed during the data analysis and the caries registration. Recruitment: The clinical study duration was from October 2010 to December 2012. Results: Overall, 270 patients were randomized, of which 15 were excluded from the study. Therefore, 255 patients were included in the analyses. The caries risk increased significantly during orthodontic treatment in group I (P < 0.0001), whereas groups II and III had unchanged caries risks. All the groups showed statistically significant increases in the numbers of cariogenic bacteria. Harms: No harms were reported during the trial. Conclusions: To avoid an increased risk of caries during orthodontic treatment, everyday use of high-fluoride toothpaste (5000 ppm F) or mouth rinse (0.2% NaF) in combination with ordinary toothpaste is recommended. Registration: The trial was not registered.

Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder.

OBJECTIVES: Increasing evidence points to the harmful effects of long-term benzodiazepine treatment. Our objective was to study the incidence of, and predictors for, long-term use of benzodiazepines and Z-drugs in bipolar disorder. METHODS: We conducted a population-based cohort study, using data from Swedish national registers. Swedish residents aged 18-75 years with a recorded diagnosis of bipolar disorder or mania between July 2006 and December 2012, and no history of benzodiazepine/Z-drug use in the past year, were included. Patients were followed for 1 year with regard to prescription fills of benzodiazepines/Z-drugs. Initiators were followed for another year during which continuous use for >6 months was defined as "long-term". Patient and prescription characteristics were investigated as potential predictors for long-term use in multivariate logistic regression models. RESULTS: Out of the 21 883 patients included, 29% started benzodiazepine/Z-drug treatment, of whom one in five became long-term users. Patients who were prescribed clonazepam or alprazolam had high odds for subsequent long-term use (adjusted odds ratios [aORs] 3.78 [95% confidence interval (CI) 2.24-6.38] and 2.03 [95% CI 1.30-3.18], respectively), compared to those prescribed diazepam. Polytherapy with benzodiazepines/Z-drugs also predicted long-term use (aOR 2.46, 95% CI 1.79-3.38), as did age ≥60 years (aOR 1.93, 95% CI 1.46-2.53, compared to age <30 years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33-2.39). CONCLUSIONS: The incidence of subsequent long-term use among bipolar benzodiazepine initiators is high. Patients on clonazepam, alprazolam or benzodiazepine/Z-drug polytherapy have the highest risk of becoming long-term users, suggesting that these treatments should be used restrictively.

Study on site-specific expression of bone formation and resorption factors in human dental follicles.

We sought to investigate site-specific expression of bone-regulatory factors expressed by human dental follicles and to compare the stimulated expression of tumour necrosis factor (ligand) superfamily, member 11/tumour necrosis factor receptor superfamily, member 11b (RANKL/OPG) in human dental follicle cells (HDFCs) from different patients. Analysis of bone-regulatory markers in follicles from 12 different study participants was performed using RT-qPCR and immunofluorescence; apical and coronal segments from each dental follicle were processed independently. Four additional dental follicles were used for cell cultures; HDFCs were precultured in osteogenic medium to initiate differentiation and thereafter cultured with 10-6 M forskolin (FSK) to activate the protein kinase cAMP (PKA/cAMP) signalling pathway and induce RANKL/OPG expression. We demonstrate that RANKL expression is significantly higher in the coronal part of follicles than in the apical part. High levels of collagen type 1 (COL1), alkaline phosphatase (ALP) and Gap-junction protein, alpha 1, 43 kDa (CX43) were expressed, whereas expression of Sp7 transcription factor (OSX), bone morphogenetic protein 2 (BMP2), colony-stimulating factor 1 (CSF-1), chemokine (C-C motif) ligand 2 (MCP1), and OPG was low in all samples. The immunofluorescence localization of CSF-1, MCP1, osteocalcin (OCN), RANKL, and BMP2 was not specific for either part of the follicles. In conclusion, a consistently high expression of CX43 suggests that gap-junction communication in HDFCs is essential for the eruption process. Furthermore, the induced expression of RANKL in HDFCs varies significantly between individuals and may relate to clinical variations in tooth eruption.