Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain, big gain.

Orthodontic forces are strongly associated with pain, the primary complaint among patients wearing orthodontic braces. Compared to other side effects of orthodontic treatment, orthodontic pain is often overlooked, with limited clinical management. Orthodontic forces lead to inflammatory responses in the periodontium, which triggers bone remodeling and eventually induces tooth movement. Mechanical forces and subsequent inflammation in the periodontium activate and sensitize periodontal nociceptors and produce orthodontic pain. Nociceptive afferents expressing transient receptor potential vanilloid subtype 1 (TRPV1) play central roles in transducing nociceptive signals, leading to transcriptional changes in the trigeminal ganglia. Nociceptive molecules, such as TRPV1, transient receptor potential ankyrin subtype 1, acid-sensing ion channel 3, and the P2X3 receptor, are believed to mediate orthodontic pain. Neuropeptides such as calcitonin gene-related peptides and substance P can also regulate orthodontic pain. While periodontal nociceptors transmit nociceptive signals to the brain, they are also known to modulate alveolar bone remodeling in periodontitis. Therefore, periodontal nociceptors and nociceptive molecules may contribute to the modulation of orthodontic tooth movement, which currently remains undetermined. Future studies are needed to better understand the fundamental mechanisms underlying neuroskeletal interactions in orthodontics to improve orthodontic treatment by developing novel methods to reduce pain and accelerate orthodontic tooth movement-thereby achieving "big gains with no pain" in clinical orthodontics.

Artificial Intelligence for 3D Reconstruction from 2D Panoramic X-rays to Assess Maxillary Impacted Canines.

The objective of this study was to explore the feasibility of current 3D reconstruction in assessing the position of maxillary impacted canines from 2D panoramic X-rays. A dataset was created using pre-treatment CBCT data from a total of 123 patients, comprising 74 patients with impacted canines and 49 patients without impacted canines. From all 74 subjects, we generated a dataset containing paired 2D panoramic X-rays and pseudo-3D images. This pseudo-3D image contained information about the location of the impacted canine in the buccal/lingual, mesial/distal, and apical/coronal positions. These data were utilized to train a deep-learning reconstruction algorithm, a generative AI. The location of the crown of the maxillary impacted canine was determined based on the output of the algorithm. The reconstruction was evaluated using the structure similarity index measure (SSIM) as a metric to indicate the quality of the reconstruction. The prediction of the impacted canine's location was assessed in both the mesiodistal and buccolingual directions. The reconstruction algorithm predicts the position of the impacted canine in the buccal, middle, or lingual position with 41% accuracy, while the mesial and distal positions are predicted with 55% accuracy. The mean SSIM for the output is 0.71, with a range of 0.63 to 0.84. Our study represents the first application of AI reconstruction output for multidisciplinary care involving orthodontists, periodontists, and maxillofacial surgeons in diagnosing and treating maxillary impacted canines. Further development of deep-learning algorithms is necessary to enhance the robustness of dental reconstruction applications.

Biomechanical analysis for different mandibular total distalization methods with clear aligners: A finite element study.

Objective: : The purpose of this finite element method (FEM) study was to analyze the biomechanical differences and tooth displacement patterns according to the traction direction, methods, and sites for total distalization of the mandibular dentition using clear aligner treatment (CAT). Methods: : A finite element analysis was performed on four FEM models using different traction methods (via a precision cut hook or button) and traction sites (mandibular canine or first premolar). A distalization force of 1.5 N was applied to the traction site by changing the direction from -30 to +30° to the occlusal plane. The initial tooth displacement and von Mises stress on the clear aligners were analyzed. Results: : All CAT-based total distalization groups showed an overall trend of clockwise or counterclockwise rotation of the occlusal plane as the force direction varied. Mesiodistal tipping of individual teeth was more prominent than that of bodily movements. The initial displacement pattern of the mandibular teeth was more predominant based on the traction site than on the traction method. The elastic deformation of clear aligners is attributed to unintentional lingual tipping or extrusion of the mandibular anterior teeth. Conclusions: : The initial tooth displacement can vary according to different distalization strategies for CAT-based total distalization. Discreet application and biomechanical understanding of traction sites and directions are necessary for appropriate mandibular total distalization.

Optineurin regulates osteoblast function in an age-dependent fashion in a mouse model of Paget's disease of bone.

Paget's disease of bone (PDB) is a degenerative disorder affecting the skull and bones. Hyperactive osteoclasts (OCs) initiate bone degradation in the early stage, followed by increased bone formation by osteoblasts (OBs) in trabecular bones during the advanced stage. This OB-OC uncoupling results in bone deformations and irregular trabecular bone patterns. Current mouse models poorly replicate the advanced-stage characteristics of PDB. Optineurin (Gene: OPTN in humans, Optn in mice, protein: OPTN) has been implicated in PDB by genetic analyses. We identified PDB-like cortical lesions associated with OC hyperactivation in an Optn knockout (Optn-/-) mouse model. However, the effects of OPTN dysfunction on OBs and trabecular bone in advanced PDB remain unclear. In this study, we used the Optn-/- mouse model to investigate trabecular bone abnormalities and OB activity in PDB. Micro-computed tomography analysis revealed severe pagetic alterations in craniofacial bones and femurs of aged Optn-/- mice, resembling clinical manifestations of PDB. Altered OB activity was observed in aged Optn-/- mice, implicating compensatory OB response in trabecular bone anomalies. To elucidate the role of OC-OB interactions in PDB, we conducted in vitro experiments using OC conditioned media (CM) to examine the effects on OB osteogenic potential. We found OC CM restored compromised osteogenic induction of Optn-/- bone marrow stromal cells (BMSCs) from young mice, suggesting OCs maintain OB activity through secreted factors. Strikingly, OC CM from aged Optn-/- mice significantly enhanced osteogenic capability of Optn-/- BMSCs, providing evidence for increased OB activity in advanced stages of PDB. We further identified TGF-ß/BMP signaling pathway in mediating the effects of OC CM on OBs. Our findings provide insights into Optn's role in trabecular bone abnormalities and OB activity in PDB. This enhances understanding of PDB pathogenesis and may contribute to potential therapeutic strategies for PDB and related skeletal disorders.

Nrf2 differentially regulates osteoclast and osteoblast differentiation for bone homeostasis.

Nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) is a master regulator of antioxidant response and protects cells from excessive oxidative stress. Nrf2 emerges as a prospective therapeutic target for metabolic bone disorders, in which the balance between osteoblastic bone formation and osteoclastic bone resorption is disrupted. However, the molecular mechanism through which Nrf2 modulates bone homeostasis remains unclear. In this study, we compared the differences in Nrf2-mediated antioxidant response and ROS regulation in osteoblasts and osteoclasts, both in vitro and in vivo. Findings indicated a close connection between the Nrf2 expression and its related antioxidant response with osteoclasts than osteoblasts. We next pharmacologically manipulated the Nrf2-mediated antioxidant response during osteoclast or osteoblast differentiation. Nrf2 inhibition enhanced osteoclastogenesis, while its activation suppressed it. In contrast, osteogenesis decreased irrespective of whether Nrf2 was inhibited or activated. These findings highlight the distinct ways in which the Nrf2-mediated antioxidant response regulates osteoclast and osteoblast differentiation, thereby contributing to the development of Nrf2 targeted therapies for metabolic bone diseases.

Comparison of maxillary anterior tooth movement between Invisalign and fixed appliances.

INTRODUCTION: This research project aimed to compare the number of maxillary incisors and canine movement between Invisalign and fixed orthodontic appliances using artificial intelligence and identify any limitations of Invisalign. METHODS: Sixty patients (Invisalign, n = 30; braces, n = 30) were randomly selected from the Ohio State University Graduate Orthodontic Clinic archive. Peer Assessment Rating (PAR) analysis was used to indicate the severity of the patients in both groups. To analyze the incisors and canine movement, specific landmarks were identified on incisors and canines using an artificial intelligence framework, two-stage mesh deep learning. Total average tooth movement in the maxilla and individual (incisors and canine) tooth movement in 6 directions (buccolingual, mesiodistal, vertical, tipping, torque, rotation) were then analyzed at a significance level of α = 0.05. RESULTS: Based on the posttreatment Peer Assessment Rating scores, the quality of finished patients in both groups was similar. In maxillary incisors and canines, there was a significant difference in movement between Invisalign and conventional appliances for all 6 movement directions (P <0.05). The greatest differences were with rotation and tipping of the maxillary canine, along with incisor and canine torque. The smallest statistical differences observed for incisors and canines were crown translational tooth movement in the mesiodistal and buccolingual directions. CONCLUSIONS: When comparing fixed orthodontic appliances to Invisalign, patients treated with fixed appliances were found to have significantly more maxillary tooth movement in all directions, especially with rotation and tipping of the maxillary canine.

Optineurin regulates NRF2-mediated antioxidant response in a mouse model of Paget's disease of bone.

Degenerative diseases affecting the nervous and skeletal systems affect the health of millions of elderly people. Optineurin (OPTN) has been associated with numerous neurodegenerative diseases and Paget's disease of bone (PDB), a degenerative bone disease initiated by hyperactive osteoclastogenesis. In this study, we found age-related increase in OPTN and nuclear factor E2-related factor 2 (NRF2) in vivo. At the molecular level, OPTN could directly interact with both NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) for up-regulating antioxidant response. At the cellular level, deletion of OPTN resulted in increased intracellular reactive oxygen species and increased osteoclastogenic potential. At the tissue level, deletion of OPTN resulted in substantially increased oxidative stress derived from leukocytes that further stimulate osteoclastogenesis. Last, curcumin attenuated hyperactive osteoclastogenesis induced by OPTN deficiency in aged mice. Collectively, our findings reveal an OPTN-NRF2 axis maintaining bone homeostasis and suggest that antioxidants have therapeutic potential for PDB.

Assessment of malalignment factors related to the Invisalign treatment time aided by automated imaging processes.

OBJECTIVES: To identify predictors regarding the type and severity of malocclusion that affect total Invisalign treatment duration based on an intraoral digital scan. MATERIALS AND METHODS: The subjects of this retrospective clinical cohort were 116 patients treated with Invisalign. A deep learning method was used for automated tooth segmentation and landmark identification of the initial and final digital models. The changes in the six degrees of freedom (DOF), representing types of malalignment, were measured. Linear regression was performed to find the contributing factors associated with treatment time. In addition, the Peer Assessment Rating (PAR) score and a composite score combining 6 DOF were correlated separately to the treatment time. RESULTS: The number of trays differed between sexes (P = .0015). The absolute maximum torque was marginally associated with the total number of trays (P = .0518), while the rest of the orthodontic tooth movement showed no correlation. The composite score showed a higher correlation with the total number of trays (P = .0045) than did individual tooth movement. Pretreatment upper and lower anterior segment PAR scores were positively associated with the treatment time (P < .001). CONCLUSIONS: There is not enough evidence to conclude that certain types of tooth movement affect the total aligner treatment time. A composite score seems to be a better predictor for total treatment time than do individual malalignment factors in aligner treatment. Upper and lower anterior malalignment factors have a significant effect on the treatment duration.

Accuracy of three-dimensional printed models derived from cone-beam computed tomography.

OBJECTIVES: To determine the accuracy of three-dimensional (3D) printed models fabricated from cone-beam computed tomography (CBCT) scans of human mandibular dry skulls in comparison with models derived from intraoral scanner (IOS) data. MATERIALS AND METHODS: Six human mandibular dry skulls were scanned by IOS and CBCT. Digital models (DMs) constructed from the IOS and CBCT data were fabricated physically using a 3D printer. The width and thickness of individual teeth and intercanine and molar widths were measured using a digital caliper. The accuracy of the DMs was compared between IOS and CBCT. Paired t-tests were used for intergroup comparisons. RESULTS: All intraclass correlation coefficient values for the three measurements (mesial-distal, buccal-lingual, width) exceeded 0.9. For the mandibular teeth, there were significant discrepancies in model accuracy between the IOS (average discrepancies of 0.18 ± 0.08 mm and 0.16 ± 0.12 mm for width and thickness, respectively) and CBCT (0.28 ± 0.07 mm for width, 0.37 ± 0.2 mm for thickness; P < .01). Intercanine (P = .38) and molar widths (P = .41) showed no significant difference between groups. CONCLUSIONS: There was a statistically significant difference in the accuracy of DMs obtained from CBCT and IOS; however, this did not seem to result in any important clinical difference. CBCT could be routinely used as an orthodontic diagnostic tool and for appliance construction.

Two-Stage Mesh Deep Learning for Automated Tooth Segmentation and Landmark Localization on 3D Intraoral Scans.

Accurately segmenting teeth and identifying the corresponding anatomical landmarks on dental mesh models are essential in computer-aided orthodontic treatment. Manually performing these two tasks is time-consuming, tedious, and, more importantly, highly dependent on orthodontists' experiences due to the abnormality and large-scale variance of patients' teeth. Some machine learning-based methods have been designed and applied in the orthodontic field to automatically segment dental meshes (e.g., intraoral scans). In contrast, the number of studies on tooth landmark localization is still limited. This paper proposes a two-stage framework based on mesh deep learning (called TS-MDL) for joint tooth labeling and landmark identification on raw intraoral scans. Our TS-MDL first adopts an end-to-end iMeshSegNet method (i.e., a variant of the existing MeshSegNet with both improved accuracy and efficiency) to label each tooth on the downsampled scan. Guided by the segmentation outputs, our TS-MDL further selects each tooth's region of interest (ROI) on the original mesh to construct a light-weight variant of the pioneering PointNet (i.e., PointNet-Reg) for regressing the corresponding landmark heatmaps. Our TS-MDL was evaluated on a real-clinical dataset, showing promising segmentation and localization performance. Specifically, iMeshSegNet in the first stage of TS-MDL reached an averaged Dice similarity coefficient (DSC) at 0.964±0.054 , significantly outperforming the original MeshSegNet. In the second stage, PointNet-Reg achieved a mean absolute error (MAE) of 0.597±0.761 mm in distances between the prediction and ground truth for 66 landmarks, which is superior compared with other networks for landmark detection. All these results suggest the potential usage of our TS-MDL in orthodontics.

A multifactorial intervention to increase adherence to oral appliance therapy with a titratable mandibular advancement device for obstructive sleep apnea: a randomized controlled trial.

PURPOSE: Obstructive sleep apnea (OSA) is a common chronic condition, associated with several conditions that account for leading causes of mortality. Adherence to treatment of a chronic condition is, along with treatment efficacy, a major determinant of treatment outcome. The aim of this study was to test whether or not a multifactorial intervention in addition to standard care increases adherence rates in patients using a titratable oral appliance for OSA. METHODS: All subjects were 18 years old or older, had a diagnosis of OSA, and were treated with an oral appliance with an embedded sensor to measure appliance wear time objectively. The control group received routine care, while the experimental subjects received an additional multifactorial intervention. Comparison of adherence was at 30 days (Phase I) and 90 days (Phase II) after appliance delivery. RESULTS: Data are reported for 82 subjects in Phase I (control 43; experimental 39) and 66 subjects in Phase II (control 36; experimental 30). There were no significant differences for age, sex, body mass index, and apnea-hypopnea index (p > 0.05) between groups. In both Phase I and Phase II, the mean number of nights the appliance was worn 4 or more hours and the mean time the appliance was worn nightly were significantly greater in the experimental than in the control group (p < 0.05). CONCLUSIONS: Interventions were well received by subjects and can be carried out by auxiliary personnel. The experimental interventions resulted in clinically important and statistically significant improvements in patient adherence to treatment.

Orthodontic loading activates cell-specific autophagy in a force-dependent manner.

INTRODUCTION: Orthodontic tooth movement (OTM) relies on bone remodeling and controlled aseptic inflammation. Autophagy, a conserved homeostatic pathway, has been shown to play a role in bone turnover. We hypothesize that autophagy participates in regulating bone remodeling during OTM in a force-dependent and cell type-specific manner. METHODS: A split-mouth design was used to load molars with 1 of 3 force levels (15, 30, or 45 g of force) in mice carrying a green fluorescent protein-LC3 transgene to detect cellular autophagy. Fluorescent microscopy and quantitative polymerase chain reaction analyses were used to evaluate autophagy activation and its correlation with force level. Cell type-specific antibodies were used to identify cells with green fluorescent protein-positive puncta (autophagosomes) in periodontal tissues. RESULTS: Autophagic activity increased shortly after loading with moderate force and was associated with the expression of bone turnover, inflammatory, and autophagy markers. Different load levels resulted in altered degrees of autophagic activation, gene expression, and osteoclast recruitment. Autophagy was specifically induced by loading in macrophages and osteoclasts found in the periodontal ligament and alveolar bone. Data suggest autophagy participates in regulating bone turnover during OTM. CONCLUSIONS: Autophagy is induced in macrophage lineage cells by orthodontic loading in a force-dependent manner and plays a role during OTM, possibly through modulation of osteoclast bone resorption. Exploring the roles of autophagy in OTM is medically relevant, given that autophagy is associated with oral and systemic inflammatory conditions.

Prediction of maxillary canine impaction using eruption pathway and angular measurement on panoramic radiographs.

OBJECTIVES: To compare the normal eruption pattern and angulation in impacted maxillary canines using panoramic radiographs to predict maxillary canine impaction. MATERIALS AND METHODS: Patients aged 6 to 15 years were classified into the normal eruption group (n = 229) and the impaction group (n = 191). At least two panoramic radiographs were taken in the normal eruption group during the eruption process of the maxillary canine. The growth pattern of the maxillary canine was analyzed using an XY coordinate system, with the tip of the maxillary lateral incisor as the origin and the tooth's long axis as the Y-axis and measurement of the relative position of the crown tip and angulation of the maxillary canine. RESULTS: The crown tips of normally erupted maxillary canines were intensively distributed along the distal surface of the maxillary lateral incisor, while those of impacted canines were widely distributed. The angulations of the normally erupted canines increased as eruption increased along the lateral incisor and then decreased at the cervical point of the lateral incisor. The angulations of the impacted canines were scattered, with no uniform pattern. CONCLUSIONS: While using the normal eruption path of the maxillary canine and the pattern of change in angulation based on the distal surface of the maxillary lateral incisor, early intervention or regular follow-up is needed to prevent maxillary canine impaction.

Understanding technology adoption by orthodontists: A quantitative study.

INTRODUCTION: Digital scanning, treatment planning, 3-dimensional imaging, and printing are changing the practice of orthodontics. These tools are adopted with the hope that treatment becomes more predictable, efficient, and effective while reducing adverse outcomes. Digital tools are impacting care, but knowledge of nationwide adoption trends and motivators is incomplete. METHODS: We aimed to identify adoption decision-makers, information sources, incentives, and barriers through the first nationwide survey of American Association of Orthodontics members on their technology adoption habits, needs, and outcomes. Data were assessed using descriptive and bivariate analyses. The survey was developed from a comprehensive qualitative interview phase as part of a mixed methodology study. RESULTS: Responses (n = 343) revealed orthodontists make adoption decisions on the basis of advice from other dentists and company representatives while rarely consulting staff or research literature. Continuing education and meetings are most effective at disseminating information to practicing doctors, whereas journals generate less impact. Key adoption incentives include added capabilities, practice efficiency, ease of implementation, and performance, whereas cost is the main barrier to purchase. Early adopters with larger practices charge higher fees than other adopters to support the costs of technologies. Treatment outcome is not a primary adoption incentive for specific technologies. CONCLUSIONS: Orthodontists positively perceive the influence of intraoral scanning, cone-beam computed tomography imaging, 3-dimensional printing, computer-aided design-computer-aided manufacturing archwires, and clear aligner therapy on their practice and patient care. The orthodontic technological transformation is underway, and knowledge of adoption can guide our transition into modern practice, in which digital tools are effective adjuncts to the specialists' expertise.

Educational debt and the gender gap: Understanding factors influencing orthodontists' career decisions.

INTRODUCTION: Orthodontic residents face challenges unparalleled to their predecessors, including competitive marketplaces, rising debt burdens, and changing demographics that have contributed to the shift in initial career choice from owner to employee. We aim to understand factors important to orthodontists at different career stages and the impact on job satisfaction through a sequential mixed methodology study. METHODS: Semistructured interviews were conducted with 25 orthodontic residents and practitioners. A survey was developed from qualitative findings that explored career decision-making of orthodontic residents and practicing orthodontists, with descriptive and bivariate statistical analyses (n = 343 orthodontists and 185 residents). RESULTS: Graduating orthodontic residents are choosing employment over ownership as their initial job, prioritizing high income to offset the educational debt. The majority of residents report thinking about their debt very often to all of the time and find it very to extremely stressful. Current residents have long-term goals of ownership, whereas practicing doctors of both genders became owners at equal frequencies. However, on average, women earn $119,000 less per year and report being the primary family caretaker more often than men. CONCLUSIONS: Excellent patient care, work-life balance, and sufficient income are the most important drivers for career choices and job satisfaction for orthodontists of all ages. Despite debt, most residents and working orthodontists report a high level of job satisfaction and would recommend the field of orthodontics to others.

Biomimetic polydopamine-laced hydroxyapatite collagen material orients osteoclast behavior to an anti-resorptive pattern without compromising osteoclasts' coupling to osteoblasts.

Polydopamine-assisted modification for bone substitute materials has recently shown great application potential in bone tissue engineering due to its excellent biocompatibility and adhesive properties. A scaffold material's impact on osteoclasts is equally as important as its impact on osteoblasts when considering tissue engineering for bone defect repair, as healthy bone regeneration requires an orchestrated coupling between osteoclasts and osteoblasts. How polydopamine-functionalized bone substitute materials modulate the activity of osteoblast lineage cells has been extensively investigated, but much less is known about their impact on osteoclasts. Moreover, most of the polydopamine-functionalized materials would need to additionally load a biomolecule to exert the modulation on osteoclast activity. Herein, we demonstrated that our biomimetic polydopamine-laced hydroxyapatite collagen (PDHC) scaffold material, which does not need to load additional bioactive agent, is sufficiently able to modulate osteoclast activity in vitro. First, PDHC showed an anti-resorptive potential, characterized by decreased osteoclast differentiation and resorption capacity and changes in osteoclasts' transcriptome profile. Next, cAMP response element-binding protein (CREB) activity was found to mediate PDHC's anti-osteoclastogenic effect. Finally, although PDHC altered clastokines expression pattern of osteoclasts, as revealed by transcriptomic and secretomic analysis, osteoclasts' coupling to osteoblasts was not compromised by PDHC. Collectively, this study demonstrated the PDHC material orients osteoclast behavior to an anti-resorptive pattern without compromising osteoclasts' coupling to osteoblasts. Such a feature is favorable for the net increase of bone mass, which endows the PDHC material with great application potential in preclinical/clinical bone defect repair.

Machine learning from clinical data sets of a contemporary decision for orthodontic tooth extraction.

OBJECTIVE: To examine the robustness of the published machine learning models in the prediction of extraction vs non-extraction for a diverse US sample population seen by multiple providers. SETTING AND SAMPLE POPULATION: Diverse group of 838 patients (208 extraction, 630 non-extraction) were consecutively enrolled. MATERIALS AND METHODS: Two sets of input features (117 and 22) including clinical and cephalometric variables were identified based on previous studies. Random forest (RF) and multilayer perception (MLP) models were trained using these feature sets on the sample population and evaluated using measures including accuracy (ACC) and balanced accuracy (BA). A technique to identify incongruent data was used to explore underlying characteristics of the data set and split all samples into 2 groups (G1 and G2) for further model training. RESULTS: Performance of the models (75%-79% ACC and 72%-76% BA) on the total sample population was lower than in previous research. Models were retrained and evaluated using G1 and G2 separately, and individual group MLP models yielded improved accuracy for G1 (96% ACC and 94% BA) and G2 (88% ACC and 85% BA). RF feature ranking showed differences between top features for G1 (maxillary crowding, mandibular crowding and L1-NB) and G2 (age, mandibular crowding and lower lip to E-plane). CONCLUSIONS: An incongruent data pattern exists in a consecutively enrolled patient population. Future work with incongruent data segregation and advanced artificial intelligence algorithms is needed to improve the generalization ability to make it ready to support clinical decision-making.