Toll-like receptor-2 induced inflammation causes local bone formation and activates canonical Wnt signaling.

It is well established that inflammatory processes in the vicinity of bone often induce osteoclast formation and bone resorption. Effects of inflammatory processes on bone formation are less studied. Therefore, we investigated the effect of locally induced inflammation on bone formation. Toll-like receptor (TLR) 2 agonists LPS from Porphyromonas gingivalis and PAM2 were injected once subcutaneously above mouse calvarial bones. After five days, both agonists induced bone formation mainly at endocranial surfaces. The injection resulted in progressively increased calvarial thickness during 21 days. Excessive new bone formation was mainly observed separated from bone resorption cavities. Anti-RANKL did not affect the increase of bone formation. Inflammation caused increased bone formation rate due to increased mineralizing surfaces as assessed by dynamic histomorphometry. In areas close to new bone formation, an abundance of proliferating cells was observed as well as cells robustly stained for Runx2 and alkaline phosphatase. PAM2 increased the mRNA expression of Lrp5, Lrp6 and Wnt7b, and decreased the expression of Sost and Dkk1. In situ hybridization demonstrated decreased Sost mRNA expression in osteocytes present in old bone. An abundance of cells expressed Wnt7b in Runx2-positive osteoblasts and ß-catenin in areas with new bone formation. These data demonstrate that inflammation, not only induces osteoclastogenesis, but also locally activates canonical WNT signaling and stimulates new bone formation independent on bone resorption.

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 numerous 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. These observations indicate that osteoclastogenesis on the endocortical and periosteal surfaces of bone is differentially controlled by vitamin A. 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 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 (EC50 ∼3nM) 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 M-CSF receptor, RANK, F4/80 and CD11b, as well as by FACS-analysis of CD11b+/F480+/Gr1- cells. The stimulation of macrophage numbers in the periosteal cell cultures was not mediated by increased M-CSF or IL-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 also 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.

Human PRH1, PRH2 susceptibility and resistance and Streptococcus mutans virulence phenotypes specify different microbial profiles in caries.

BACKGROUND: Lifestyle- and sucrose-dependent polymicrobial ecological shifts are a primary cause of caries in populations with high caries prevalence. In populations with low prevalence, PRH1, PRH2 susceptibility and resistance phenotypes may interact with the Streptococcus mutans adhesin cariogenicity phenotype to affect caries progression, but studies are lacking on how these factors affect the microbial profile of caries. METHODS: We analysed how the residency and infection profiles of S. mutans adhesin (SpaP A/B/C and Cnm/Cbm) phenotypes and commensal streptococci and lactobacilli influenced caries progression in a prospective case-referent sample of 452 Swedish adolescents with high (P4a), moderate (P6), and low (P1) caries PRH1, PRH2 phenotypes. Isolates of S. mutans from participants were analysed for adhesin expression and glycosylation and in vitro and in situ mechanisms related to caries activity. FINDINGS: Among adolescents with the resistant (P1) phenotype, infection with S. mutans high-virulence phenotypes was required for caries progression. In contrast, with highly (P4a) or moderately (P6) susceptible phenotypes, caries developed from a broader polymicrobial flora that included moderately cariogenic oral commensal streptococci and lactobacilli and S. mutans phenotypes. High virulence involved unstable residency and fluctuating SpaP ABC, B-1, or Cnm expression/glycosylation phenotypes, whereas low/moderate virulence involved SpaP A phenotypes with stable residency. Adhesin phenotypes did not display changes in individual host residency but were paired within individuals and geographic regions. INTERPRETATION: These results suggest that receptor PRH1, PRH2 susceptibility and resistance and S. mutans adhesin virulence phenotypes specify different microbial profiles in caries. FUNDING: Swedish Research Council and funding bodies listed in the acknowledgement section.

Pre-fabricated chain retainers as an alternative to traditional retainers.

Background/purpose: Preserving the outcome of orthodontic treatment is both important and challenging. However, there is insufficient evidence regarding the best way to ensure long-term treatment outcome. The aim of this study was to evaluate a pre-fabricated chain retainer (PFCR) in terms of: ability to maintain satisfactory treatment outcomes; periodontal and dental health; complications; and patient satisfaction. Materials and methods: Overall, 130 patients who had completed orthodontic treatment with a fixed appliance during the period 2016-2019 (follow-up time range, 24-55 months) at a specialist orthodontic clinic in Varberg, Sweden and who had a PFCR in the lower jaw were invited to take part in the study. Little's irregularity index (LII) was recorded on dental casts. Caries, gingivitis, calculus, probing pocket depth, and gingival retractions were registered during clinical examinations. Patient satisfaction and retainer complications were evaluated using a questionnaire. Results: In total, 76 patients (58.5%) agreed to participate. All patients, except for one, had their retainer still in place, and the complication rate was 40%. The LII scores were in the range of 0-4 mm (mean, 1.42 mm). At the retainer site, 82% had calculus, 74% had gingivitis, 1% had pocket depth >4 mm, 10.5% had gingival retractions >2 mm, and 0% had caries. All the patients expressed satisfaction with their retainer. Conclusion: PFCRs exhibit characteristics similar to those of traditional bonded retainers in terms of complications, stability, side-effects and patient experience. Therefore, they can be considered a viable alternative to traditional retainers installed in the lower anterior teeth.

Dentofacial characteristics of children and adolescents with foetal alcohol spectrum disorders: a comparison with matched controls.

BACKGROUND: Foetal alcohol spectrum disorders (FASD) include somatic and neurological developmental disturbances after prenatal alcohol exposure, including facial anomalies. However, the knowledge of the orthodontic skeletal and dental cephalometric relations in this group is limited. The aim of the study was to assess the dentofacial characteristics of children and adolescents with FASD and to compare them with a matched control group. METHODS: The study group comprised all available children and adolescents diagnosed with FASD (> 7 years of age) in whom good quality cephalograms were available. The control group comprised non-syndromic, orthodontically untreated children with normal occlusion and skeletal relations matched with age and gender. Cephalometric analysis included eighteen linear and angular measurements. The general linear model for repeated measures regarding age, gender and the type of FASD was applied. RESULTS: The group with FASD included 35 individuals (21 girls and 14 boys) aged 7-18 years including 21 with foetal alcohol syndrome. The mean age in the study and the control group was 12.8 years (SD, range 3.2, 7.1-18.1) and 13.0 (SD, range 2.9, 9.1-18.1), respectively. Statistically significant differences between the groups were found in 15 out of 18 of the cephalometric measurements (83%). In children with FASD the mandible was more retrusive, the incisors were more proclined and the mandibular incisors and the lips were more protruded when compared with controls. There was no significant evidence of an influence of age, gender or FASD type. CONCLUSIONS: Dentofacial characteristics of children and adolescents with FASD significantly differ from controls. Early orthodontic diagnosis and prophylaxis should play a part of the interdisciplinary care of patients in this group.

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.

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.

Open Bite Malocclusion and Orofacial Dysfunction in Patients with Myotonic Dystrophy Type 1 and Duchenne Muscular Dystrophy.

Open bite (OB) is a common malocclusion in individuals with orofacial dysfunction and syndromes, especially in neuromuscular diseases. OBJECTIVES: The objectives were to explore the prevalence of OB in myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and to create and compare orofacial dysfunction profiles. METHODS: In this database study, 143 individuals with DM1 and 99 with DMD were included. The Mun-H-Center questionnaire and observation chart were used together with the Nordic Orofacial Test -Screening (NOT-S) to create orofacial dysfunction profiles. OB was categorised as: lateral (LOB); anterior (AOB); severe anterior (AOBS); or both types of anterior OB (AOBTot). Descriptive and multivariate statistics were used to compare the OB prevalence and to study associations with orofacial variables, respectively. RESULTS: There was a statistically significant difference in OB prevalence between the DM1 (37%) and DMD (49%) groups (p = 0.048). LOB was seen in < 1% of DM1 and 18% of DMD. LOB was associated with macroglossia and closed mouth posture, AOB with hypotonic lips, and open mouth posture and AOBS with hypotonic jaw muscles. The orofacial dysfunction profiles showed similar patterns, although the mean NOT-S total scores for DM1 and DMD were 4.2±2.8 (median 4.0, min-max 1-8) and 2.3±2.0 (median 2.0, min-max 0-8), respectively. LIMITATIONS: The two groups were not age- or gender-matched. CONCLUSION: OB malocclusion is common in patients with DM1 and DMD and is associated with different types of orofacial dysfunction. This study highlights the need for multi-disciplinary assessments to support tailored treatment strategies that improve or sustain orofacial functions.

Assessment of thin bony structures using cone-beam computed tomography.

OBJECTIVES: To investigate the validity and reliability of marginal bone level measurements on cone-beam computed tomography (CBCT) images of thin bony structures using various reconstruction techniques, two image resolutions, and two viewing modes. MATERIALS AND METHODS: CBCT and histologic measurements of the buccal and lingual aspects of 16 anterior mandibular teeth from 6 human specimens were compared. Multiplanar (MPR) and three-dimensional (3D) reconstructions, standard and high resolutions, and gray scale and inverted gray scale viewing modes were assessed. RESULTS: Validity of radiologic and histologic comparisons were highest using the standard protocol, MPR, and the inverted gray scale viewing mode (mean difference = 0.02 mm) and lowest using a high-resolution protocol and 3D-rendered images (mean difference = 1.10 mm). Mean differences were significant (P < .05) at the lingual surfaces for both reconstructions, viewing modes (MPR windows), and resolutions. CONCLUSIONS: Varying the reconstruction technique and viewing mode does not improve the observer's ability to visualize thin bony structures in the anterior mandibular region. The use of 3D-reconstructed images should be avoided when thin cortical borders are suspected. The small difference when using a high-resolution protocol is unjustified due to the higher radiation dose required. Previous studies have focused on technical parameters; the present study explores the next link in the imaging chain.

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.

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.

Children and adolescents with speech sound disorders are more likely to have orofacial dysfunction and malocclusion.

BACKGROUND: Children with speech sound disorders (SSD) form a heterogeneous group that differs in terms of underlying cause and severity of speech difficulties. Orofacial dysfunction and malocclusions have been reported in children with SSD. However, the association is not fully explored. OBJECTIVES: Our aims were to describe differences in orofacial function and malocclusion between a group of children and adolescents with compared to without SSD and to explore associations between those parameters among the group with SSD. METHODS: A total of 105 participants were included, 61 children with SSD (6.0-16.7 years, mean age 8.5 ± 2.8, 14 girls and 47 boys) and 44 children with typical speech development (TSD) (6.0-12.2 years, mean age 8.8 ± 1.6, 19 girls and 25 boys). Assessments of orofacial function included an orofacial screening test and assessment of bite force, jaw stability, chewing efficiency, and intraoral sensory-motor function. Possible malocclusions were also assessed. RESULT: Children with SSD had both poorer orofacial function and a greater prevalence of malocclusion than children with TSD. Furthermore, children with SSD and poorer orofacial function had a greater risk of malocclusion. CONCLUSION: Our result suggests that children with SSD are more prone to having poorer orofacial function and malocclusion than children with TSD. This illustrates the importance of assessing coexisting orofacial characteristics in children with SSD, especially since orofacial dysfunction may be linked to an increased risk of malocclusion. This result highlights the need for a multiprofessional approach.

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.

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.

WNT16 is Robustly Increased by Oncostatin M in Mouse Calvarial Osteoblasts and Acts as a Negative Feedback Regulator of Osteoclast Formation Induced by Oncostatin M.

BACKGROUND: Bone loss is often observed adjacent to inflammatory processes. The WNT signaling pathways have been implicated as novel regulators of both immune responses and bone metabolism. WNT16 is important for cortical bone mass by inhibiting osteoclast differentiation, and we have here investigated the regulation of WNT16 by several members of the pro-inflammatory gp130 cytokine family. METHODS: The expression and regulation of Wnt16 in primary murine cells were studied by qPCR, scRNAseq and in situ hybridization. Signaling pathways were studied by siRNA silencing. The importance of oncostatin M (OSM)-induced WNT16 expression for osteoclastogenesis was studied in cells from Wnt16-deficient and wild-type mice. RESULTS: We found that IL-6/sIL-6R and OSM induce the expression of Wnt16 in primary mouse calvarial osteoblasts, with OSM being the most robust stimulator. The induction of Wnt16 by OSM was dependent on gp130 and OSM receptor (OSMR), and downstream signaling by the SHC1/STAT3 pathway, but independent of ERK. Stimulation of the calvarial cells with OSM resulted in enhanced numbers of mature, oversized osteoclasts when cells were isolated from Wnt16 deficient mice compared to cells from wild-type mice. OSM did not affect Wnt16 mRNA expression in bone marrow cell cultures, explained by the finding that Wnt16 and Osmr are expressed in distinctly different cells in bone marrow, nor was osteoclast differentiation different in OSM-stimulated bone marrow cell cultures isolated from Wnt16-/- or wild-type mice. Furthermore, we found that Wnt16 expression is substantially lower in cells from bone marrow compared to calvarial osteoblasts. CONCLUSION: These findings demonstrate that OSM is a robust stimulator of Wnt16 mRNA in calvarial osteoblasts and that WNT16 acts as a negative feedback regulator of OSM-induced osteoclast formation in the calvarial bone cells, but not in the bone marrow.

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.

Primary Sjögren's Syndrome: A Retrospective Cohort Study of Burden of Illness in Sweden.

INTRODUCTION: Primary Sjögren's syndrome (pSS) is an autoimmune disease that affects salivary and lachrymal glands and is associated with complex extraglandular manifestations. This study investigates the clinical and economic burden and disease course of pSS in Sweden. METHODS: This retrospective cohort study utilizes data from Swedish national registries and consists of patients at least 18 years of age diagnosed in secondary care with pSS, and matched members of the Swedish general population. Healthcare resource utilization (HRU) and costs were compared. The clinical burden of pSS during follow-up was explored via year-on-year prevalence of and time-to-first extraglandular manifestation. Employment status and retirement rates were used to investigate the impact of pSS on productivity. RESULTS: A total of 8884 patients with pSS and 88,233 general population comparators were included. Patients with pSS had significantly higher rates of HRU and higher healthcare costs than matched comparators, including twice as many outpatient visits. Costs were highest in year 1 post index before reducing in years 2 and 3 and stabilizing thereafter. Almost two-thirds of patients received their index diagnosis during an outpatient visit, and < 30% of diagnoses were from rheumatology departments. Overall, 41% of patients experienced a healthcare encounter that included a relevant extraglandular manifestation code during follow-up. Patients with pSS had significantly higher odds of early retirement than the general population at 5 years post index. CONCLUSIONS: Patients with pSS experience a high clinical and economic disease burden in Sweden.

Primary Sjögren's syndrome (pSS) is an autoimmune disease that typically affects the secretory glands that produce tears, saliva, and other secretions. Patients can experience debilitating fatigue and can also develop conditions in other parts of the body, commonly including arthritis and Raynaud's phenomenon. This study investigated the burden and disease course of pSS in Sweden. Swedish national registry data were used to match adult patients diagnosed with pSS, with members of the Swedish general population. The use of healthcare resources and their associated costs were compared. The clinical burden of pSS during patient follow-up was explored via year-on-year occurrence and cumulative incidence of extraglandular symptoms. Employment and retirement rates were used to investigate the effect of pSS on patient productivity. A total of 8884 patients with pSS and 88,233 members of the general population were included in the study. Patients with pSS had higher use of healthcare resources and higher associated costs than members of the general population, including twice as many outpatient visits. Costs were highest in the first year after diagnosis, reducing and stabilizing over the following 7 years. Overall, 41% of patients had a healthcare encounter that included a relevant extraglandular symptom code during follow-up. Almost two-thirds of patients were diagnosed during an outpatient visit, and < 30% of diagnoses were from rheumatology departments. Patients with pSS were at a greater risk of early retirement than the general population at 5 years post-diagnosis. These results indicate that patients with pSS experience a high disease burden in Sweden.

A Superimposition-Based Cephalometric Method to Quantitate Craniofacial Changes.

To assess the craniofacial changes related to growth and/or to orthodontic and orthognathic treatments, it is necessary to superimpose serial radiographs on stable structures. However, conventional superimposition provides only a graphical illustration of these changes. To increase the precision of growth and treatment evaluations, it is desirable to quantitate these craniofacial changes. The aims of this study were to (1) evaluate a superimposition-based cephalometric method to process numerical data for craniofacial growth changes and (2) identify a valid, reliable, and feasible method for superimposition. Forty pairs of cephalograms were analyzed at T1 and T2 (mean age 9.9 and 15.0 years, respectively). The superimposition-based cephalometric method involved relating the sagittal and vertical measurements on the T2 radiographs to the nasion and sella landmarks on the T1 radiographs. Validity and reliability were evaluated for three superimposition methods: the sella-nasion (SN); the tuberculum sella-wing (TW); and Björk's structural. Superimposition-based cephalometrics can be used to quantify craniofacial changes digitally. The numerical data from the superimposition-based cephalometrics reflected a graphical illustration of superimposition and differed significantly from the data acquired through conventional cephalometrics. Superimposition using the TW method is recommended as it is valid, reliable, and feasible.