Primary Failure of Dental Eruption Due to Variants Parathyroid Hormone Receptor 1: Retrospective Study and Proposal of Guidelines Treatment.

OBJECTIVE: Primary failure of eruption is characterized by a nonsyndromic defect in tooth eruption in the absence of mechanical obstruction. It is correlated to rare heterozygous variants in the parathyroid hormone receptor 1 gene. The management of primary failure of eruption is complex because many therapies are ineffective. The present study aimed to compare the clinical outcomes of our patients with the findings reported in the literature, and to propose a treatment guideline based on the literature and our experience. METHODS: Retrospective study of patients affected by primary dental eruption failure in the department and analyse of the results and compare with those of the litterature. RESULTS: Twelve patients belonging to 5 families (9 males, 3 females; 13-52 y old) diagnosed and treated in the maxillofacial surgery and stomatology department of the Lille University Hospital were included. All patients showed posterior tooth involvement, and most patients showed bilateral defects. None of the affected teeth had coronal alveolar bone, whereas 6 patients showed root resorption in the affected teeth. Genetic analyses, performed on 11 patients, identified a parathyroid hormone receptor 1 disease-causing variant in 7 of them (63%). Multidisciplinary treatment was required to rehabilitate these patients. Orthodontic interventions, even at an early age, are difficult in affected teeth, which are often blocked or have internal resorption. Moreover, retention of these affected teeth during growth leads to dentoskeletal malocclusions, requiring difficult surgical management in the long term. Therefore, early extraction of these teeth is frequently recommended once the diagnosis has been confirmed. An implant-borne prosthetic rehabilitation can then be achieved at the end of growth after correction of the jaw discrepancy. In case of a late diagnosis, other surgical or noninvasive techniques may be used depending on the clinical situation. Distraction osteogenesis or segmental osteotomy could be discussed for patients with mild phenotypes. CONCLUSIONS: Early diagnosis of primary eruption defects is crucial to offer appropriate management as early as possible, and so to avoid late complicated treatments.

ACTN3 genotype influences masseter muscle characteristics and self-reported bruxism.

OBJECTIVES: Main aim of the study was to explore the association between genetic polymorphisms in ACTN3 and bruxism. Secondary objectives included masseter muscle phenotypes assessment between bruxers and non-bruxers and according to genetic polymorphisms in ACTN3. MATERIALS AND METHODS: Fifty-four patients undergoing orthognathic surgery for correction of their malocclusion were enrolled. Self-reported bruxism and temporomandibular disorders status were preoperatively recorded. Saliva samples were used for ACTN3 genotyping. Masseter muscle samples were collected bilaterally at the time of orthognathic surgery to explore the muscle fiber characteristics. RESULTS: There were significant differences in genotypes for rs1815739 (R577X nonsense) (p = 0.001), rs1671064 (Q523R missense) (p = 0.005), and rs678397 (intronic variant) (p = 0.001) between bruxers and non-bruxers. Patients with self-reported bruxism presented a larger mean fiber area for types IIA (p = 0.035). The mean fiber areas in individuals with the wild-type CC genotype for rs1815739 (R577X) were significantly larger for type IIA fibers (1394.33 µm2 [572.77 µm2 ]) than in those with the TC and TT genotypes (832.61 µm2 [602.43 µm2 ] and 526.58 µm2 [432.21 µm2 ] [p = 0.014]). Similar results for Q523R missense and intronic variants. CONCLUSIONS: ACTN3 genotypes influence self-reported bruxism in patients with dentofacial deformity through specific masseter muscle fiber characteristics.

A Systematic Review of Rat Models With Temporomandibular Osteoarthritis Suitable for the Study of Emerging Prolonged Intra-Articular Drug Delivery Systems.

PURPOSE: Development of minimally invasive therapies for temporomandibular joint osteoarthritis (TMJOA) has focused on drug intra-articular injections to avoid the systemic adverse effects experienced when these substances are administered orally. Therefore, we performed a systematic review to answer the question "Which method of induction of a TMJOA-related pain model in rats leads to prolonged painful symptoms, allowing the best assessment of a sustained drug delivery system?" MATERIALS AND METHODS: Following the PRISMA guidelines, we searched MEDLINE for papers published from 1994 to July 2020 on a TMJ arthritis model using rats. We identified the means of pain induction and of nociception assessment. We assessed protocol bias using an adaptation of the QUADAS-2 tool. Animal selection, the reference standard method of pain assessment, applicability of a statistical assessment, and flow and timing were assessed. RESULTS: Of the 59 full papers we reviewed, 41 performed no pain assessment after the first 7 days following induction of the TMJ-related pain model. We eventually identified 18 long-term TMJOA-related pain models. Pain was induced by injection of toxic substances, most commonly Freund's complete adjuvant (50 µg per 50 µl), formalin at various concentrations, or monosodium iodoacetate (0,5 mg per 50 µl), into the TMJ, or by physical methods. Few studies reported data on pain after 21 days of follow-up. Heterogeneity of induction methods, pain assessment methods, and flow and timing biases precluded a meta-analysis. CONCLUSIONS: Given that pain is 1 of the main symptoms of TMJOA, experimental study protocols should include long-term pain assessment.

A New Orbito-Zygomatic Complex Reconstruction Technique Using Computer-Aided Design and Manufacturing-Assisted Harvest of Autologous Calvarial Bone in Cases of Orbito-Zygomatic Benign Tumor.

The orbito-zygomatic complex (OZC) includes several key structures, and its destruction leads to the impairment of functional activities such as nutrition, communication, nasal support, and vision. Management of benign tumors of the OZC is therefore a surgical challenge because of the necessity for reconstruction of these elements. Autogenous bone is considered the gold standard for reconstruction. Nevertheless, there is difficulty related to the complex anatomy and distorted skeletal anatomic landmarks, which require precise work in the case of bone grafts. The aim of this report is to propose a new reconstruction technique consisting of OZC reconstruction with computer-aided design and manufacturing of autologous calvarial bone. Three cases are presented. After performing tumor resection using computer-aided design and manufacturing cutting guides, we used a piezotome to perform osteotomies and preserve the periosteum and sinus mucosa. The SinpliciTi system (Materialise, Châtillon, France) allowed us to make cutting guides and a 3-dimensional surgical plan of the shapes and ideal positions of the calvarial bony plates for the OZC reconstruction. Calvarial osteotomies were performed using a piezotome through the polyamide calvarial cutting guide to obtain the shapes designed beforehand. Once the samples were collected, the shapes could be assembled ex vivo and then put in place through a minimally invasive approach. We discuss the advantages and limitations of our reconstruction method and its place in the management of OZC reconstruction.

Pre-operative parafunctional or dysfunctional oral habits are associated with the temporomandibular disorders after orthognathic surgery: An observational cohort study.

BACKGROUND: Temporomandibular disorders (TMDs) are frequent and disabling, and hence, preventing them is an important health issue. Combining orthodontic and surgical treatments for malocclusions has been shown to affect temporomandibular joint (TMJ) health. However, publications regarding the risk factors that predict negative TMJ outcomes after orthognathic surgery are scarce. OBJECTIVE: Present prospective cohort study was conducted to identify an association between pre-operative dysfunctional/parafunctional oral habits and the presence of TMD symptoms after orthognathic surgery. METHOD: We included 237 patients undergoing orthodontics and surgical treatment for malocclusions associated with dentofacial deformities within the Department of Oral and Maxillofacial Surgery of the University of Lille. Their parafunctional and dysfunctional oral habits were recorded through clinical examination along with the presence of TMD symptoms before and after the surgery. According to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) classification, the TMD symptoms studied were myalgia, arthralgia, disc displacement with or without reduction. RESULTS: Multivariate analysis revealed significant associations among bruxism (odds ratio [OR] 3.17 [1.066; 9.432]), lingual interposition (OR 4.241 [1.351; 13.313]), as well as primary swallowing (OR 3.54 [1.225; 10.234]) and the presence of postoperative symptoms of myalgia. Moreover, a significant association was observed between the presence of any dysfunctional oral habit and postoperative disc displacement with reduction (OR 4.611 [1.249; 17.021]). CONCLUSION: Bruxism and dysfunctional oral habits were shown to be risk factors for the presence of TMD symptoms also after combined orthodontic and surgical treatment. Treating such habits before orthognathic surgery should help prevent TMD.

Mandibular Osteomyelitis Following Implant Placement.

PURPOSE: Mandibular osteomyelitis is relatively rare except in cases of osteoradionecrosis or medication-related osteonecrosis. The purpose of this case report is to highlight a rare but devastating complication of dental implant surgery. MATERIALS AND METHODS: The case of a patient who developed mandibular osteomyelitis after implant placement, which was resistant to long-term antibiotic therapy and required radical surgical treatment with fibular free flap reconstruction, is reviewed as is the related literature. RESULTS: The most frequent etiologies are odontogenic and traumatic; however, hematogenous spread also exists. It usually affects patients with systemic conditions, such as diabetes mellitus, malnutrition, malignancy, or immune deficiency. The infection is usually polymicrobial. Concerning dental implant complications, the literature is comprehensive on the mechanical etiologies of implant failure and the infectious etiologies of peri-implantitis. Mandibular osteomyelitis treatment is a long and challenging process requiring long-term antibiotic therapy and multiple surgeries. CONCLUSION: The pathophysiology and treatment of mandibular osteomyelitis are discussed.

ENPP1 and ESR1 genotypes associated with subclassifications of craniofacial asymmetry and severity of temporomandibular disorders.

INTRODUCTION: We investigated whether ACTN3, ENPP1, ESR1, PITX1, and PITX2 genes which contribute to sagittal and vertical malocclusions also contribute to facial asymmetries and temporomandibular disorders (TMD) before and after orthodontic and orthognathic surgery treatment. METHODS: One hundred seventy-four patients with a dentofacial deformity were diagnosed as symmetric or subdivided into 4 asymmetric groups according to posteroanterior cephalometric measurements. TMD examination diagnosis and jaw pain and function (JPF) questionnaires assessed the presence and severity of TMD. RESULTS: Fifty-two percent of the patients were symmetric, and 48% were asymmetric. The asymmetry classification demonstrated significant cephalometric differences between the symmetric and asymmetric groups, and across the 4 asymmetric subtypes: group 1, mandibular body asymmetry; group 2, ramus asymmetry; group 3, atypical asymmetry; and group 4, C-shaped asymmetry. ENPP1 SNP-rs6569759 was associated with group 1 (P = 0.004), and rs858339 was associated with group 3 (P = 0.002). ESR1 SNP-rs164321 was associated with group 4 (P = 0.019). These results were confirmed by principal component analysis that showed 3 principal components explaining almost 80% of the variations in the studied groups. Principal components 1 and 2 were associated with ESR1 SNP-rs3020318 (P <0.05). Diagnoses of disc displacement with reduction, masticatory muscle myalgia, and arthralgia were highly prevalent in the asymmetry groups, and all had strong statistical associations with ENPP1 rs858339. The average JPF scores for asymmetric subjects before surgery (JPF, 7) were significantly higher than for symmetric subjects (JPF, 2). Patients in group 3 had the highest preoperative JPF scores, and groups 2 and 3 were most likely to be cured of TMD 1 year after treatment. CONCLUSIONS: Posteroanterior cephalometrics can classify asymmetry into distinct groups and identify the probability of TMD and genotype associations. Orthodontic and orthognathic treatments of facial asymmetry are effective at eliminating TMD in most patients.

Maxillary Reconstruction for Sinus Lift Complications With Oro-Antral Fistula: The Le Fort I Approach.

Although sinus lift procedures are reliable, some complications can lead to serious maxillary sequelae, including the development of oro-antral fistula (OAF). Maxillary reconstruction in such patients presents a challenge owing to sinus floor alterations, graft remnants, chronic infection, and morbidity from the original sinus lift approach. The current study describes our technique of maxillary reconstruction using a Le Fort 1 approach following major sinus lift complications with associated residual OAF. This technique provides excellent access for sinus curettage, OAF closure, and osseous reconstruction. It allowed a successful rehabilitation in our patients, with no implant loss and good functional and esthetic results.

Le Fort II Setback Osteotomy to Correct Naso-Ethmoido-Maxillary Protrusion.

BACKGROUND: Marked class II dentofacial deformity associated with centrofacial protrusion may be difficult to treat successfully. The purpose of this article was to report on Le Fort II setback osteotomy (LIISBO) to correct Naso-Ethmoido-Maxillary Protrusion (NEMP), to describe its indications and surgical techniques, and to analyze aesthetic and occlusal changes. MATERIALS AND METHODS: From November 2011 to November 2014, patients with NEMP, treated with LIISBO, were included in the study. Cephalometric analysis of Delaire was performed before and 1 year after surgery. Skeletal and soft tissues movements were measured between preoperative and postoperative lateral cephalographs. RESULTS: Fourteen patients were treated in our department by LIISBO. Ten patients were analyzed and presented a stable class I occlusion with reliable aesthetic results. The mean maxillary setback was -2.8 mm at nasopalatal point (Np), -3.1 mm at A point, and -3.7 mm at Pti (inferior pterygomaxilar point). The mean maxillary impaction was -2.4 mm at Np, -3 mm at A point, and -0.6 mm at Pti. The B, mental, and pogonion points showed an advancement with an average of +7.4, +7.9, and +7.7 mm, respectively. Measured soft tissues variations showed a backward movement of the nasal tip, the subnasal point, and the upper lip of -1.5, -1.6, and -0.7 mm, respectively. The lower lip, sublabial point, and the skin pogonion were advanced by +3.2, +5.4, and +6.2 mm, respectively. CONCLUSIONS: Le Fort II setback osteotomy may be regarded as the ideal treatment for adult patient presenting a NEMP syndrome.

A Cheap Hand-Made Mandibular External Fixator?

The external mandibular fixator is one of the tools that maxillofacial have to contain complex fractures, in particular in the context of ballistic traumas or comminuted fractures.The authors present a craft external fixator inspired from Joe Hall Morris fixation. This technique, particularly cheap, can be an alternative to a conventional external fixator. The authors report their advices and tricks to guide the implementation of that external fixator and avoid pitfalls. Indications of this surgical device are discussed.

Extensive Inflammatory Gingival Tumor in a Young Nonsmoking Woman: Back to Basics.

Tuberculous lesions of the oral cavity are rare and can be a diagnostic challenge, particularly in young immunocompetent patients. Most of the cases in the literature are secondary to pulmonary disease, whereas primary form is uncommon. This paper presents a case of gingival tuberculosis in a 26-year-old Indian female patient, manifesting as a rapidly extensive ulcer. The diagnosis was confirmed by histopathology and immunological investigations. Although oral manifestations of tuberculosis are rare, clinicians should include them in the differential diagnosis of various types of oral ulcers. An early diagnosis with a prompt treatment can prevent complications and potential contaminations.

Squamous cell carcinoma of the maxilla in a patient with basal cell nevus syndrome.

Basal cell nevus syndrome (BCNS) is a rare autosomal dominant disorder with complete penetrance and variable expressivity. This syndrome is characterized by developmental anomalies, such as odontogenic keratocysts of the jaws, multiple basal cell carcinomas, and skeletal abnormalities. Various neoplasms or hamartomas were observed in association with BCNS.We report on a 45-year-old female patient who presented with a tumefaction of the right maxillary region. After correlating clinical, radiographic, and histological features, diagnosis of BCNS associated with squamous cell carcinoma of the right maxillary sinus was made. A surgical treatment was performed. Because of poor compliance and delayed healing, the postoperative radiotherapy was postponed. Three months after the procedure, the patient has developed symptoms of tumoral activity.This clinical report highlights the importance of early diagnosis of BCNS and strict follow-up to prevent severe complications such as squamous cell carcinoma.

Condylar hyperplasia: correlation between clinical, radiological, scintigraphic, and histologic features.

PURPOSE: The objectives of this study were to compare demographic, clinical, radiographic, scintigraphic, and histologic differences between the 2 main types of condylar hyperplasia (CH) and to suggest a new therapeutic management based on such findings. METHODS: This was a retrospective study based on 28 patients who presented either vertical (group 1) or horizontal (group 2) forms of CH and underwent surgical treatment. Every patient had a complete preoperative clinical and radiological examination as well as a single-photon emission computed tomography scan. A histologic analysis of each resected condyle was performed. These various parameters were then compared in the 2 patient groups. RESULTS: The mean age at time of the diagnosis was 25.8 years (range, 12-50 years), and there were 22 females and 6 males. Nineteen patients had the vertical form of CH, and 9 had the horizontal form. Scintigraphic analysis showed moderate to extensive radionucleotide uptake in cases with rapid growth. Four cases had negative single-photon emission computed tomography scan uptake, and all were vertical forms, but there was no statistically significant difference between the 2 groups. The histologic analysis showed both a global thickening of the cartilage cap and of the prechondroblastic cells layer with no statistically significant difference between the 2 groups. CONCLUSIONS: Condylar hyperplasia is a pathologic condition affecting mainly young females and whose origin remains unknown. Single-photon emission computed tomography scans as an indicator of the rapidity of the disease progress are essential in assessing the condylar hyperplasia and to guide the therapeutic approach.

Nodal pathway genes are down-regulated in facial asymmetry.

PURPOSE: Facial asymmetry is a common comorbid condition in patients with jaw deformation malocclusion. Heritability of malocclusion is advancing rapidly, but very little is known regarding genetic contributions to asymmetry. This study identifies differences in expression of key asymmetry-producing genes that are down-regulated in patients with facial asymmetry. METHODS: Masseter muscle samples were collected during bilateral sagittal split osteotomy orthognathic surgery to correct skeletal-based malocclusion. Patients were classified as class II or III and open or deep bite malocclusion with or without facial asymmetry. Muscle samples were analyzed for gene expression differences on Affymetrix HT2.0 microarray global expression chips. RESULTS: Overall gene expression was different for asymmetric patients compared with other malocclusion classifications by principal component analysis (P < 0.05). We identified differences in the nodal signaling pathway, which promotes development of mesoderm and endoderm and left-right patterning during embryogenesis. Nodal and Lefty expression was 1.39- to 1.84-fold greater (P < 3.41 × 10), whereas integral membrane Nodal modulators Nomo1,2,3 were -5.63 to -5.81 (P < 3.05 × 10) less in asymmetry subjects. Fold differences among intracellular pathway members were negative in the range of -7.02 to -2.47 (P < 0.003). Finally Pitx2, an upstream effector of Nodal known to influence the size of type II skeletal muscle fibers was also significantly decreased in facial asymmetry (P < 0.05). CONCLUSIONS: When facial asymmetry is part of skeletal malocclusion, there are decreases in nodal signaling pathway genes in masseter muscle. This data suggest that the nodal signaling pathway is down-regulated to help promote development of asymmetry. Pitx2 expression differences also contributed to both skeletal and muscle development in this condition.

ACTN3 R577X genotypes associate with Class II and deepbite malocclusions.

INTRODUCTION: α-Actinins are myofibril anchor proteins that influence the contractile properties of skeletal muscles. ACTN2 is expressed in slow type I and fast type II fibers, whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (ie, changing 577RR to 577XX, the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminishes fast contractile ability, enhances endurance performance, and reduces bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in the masseter muscle of orthognathic surgery patients to determine the genotype associations with malocclusion. METHODS: Clinical information, masseter muscle biopsies, and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 single nucleotide polymorphisms, real-time polymerase chain reaction quantitation of muscle gene message, and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. RESULTS: Muscle mRNA expression level was significantly different for ACTN3 single nucleotide polymorphism genotypes (P <0.01). The frequency of ACTN3 genotypes was significantly different for the sagittal and vertical classifications of malocclusion, with the clearest association being elevated 577XX genotype in skeletal Class II malocclusion (P = 0.003). This genotype also resulted in significantly smaller diameters of fast type II fibers in masseter muscles (P = 0.002). CONCLUSION: ACTN3 577XX is overrepresented in subjects with skeletal Class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in subjects with deepbite malocclusion, suggesting that muscle differences contribute to variations in vertical facial dimensions.

Augmented reality in implantology: Virtual surgical checklist and augmented implant placement.

OBJECTIVES: Aim of the present study was to create a pedagogical checklist for implant surgical protocol with an augmented reality (AR) guided freehand surgery to inexperienced surgeons using a head mounted display (HMD) with tracking. METHODS: The anatomical model of a patient with two missing mandibular teeth requiring conventional single-tooth implants was selected. The computed tomography (CT) scans were extracted and imported into segmentation and implant planning software. A Patient-specific dental splint through an intermediate strut, supported 3D-printed QR code. A checklist was generated to guide surgical procedure. After tracking, the AR-HMD projects the virtual pre-surgical plan (inferior alveolar nerve (IAN), implant axis, implant location) onto the real 3D-printed anatomical models. The entire drilling sequence was based on the manufacturer's recommendations, on 3D-printed anatomical models. After the implant surgical procedure, CT of the 3D-printed models was performed to compare the actual and simulated implant placements. All procedures in the study were performed in accordance with the Declaration of Helsinki. RESULTS: In total, two implants were placed in a 3D-printed anatomical model of a female patient who required implant rehabilitation for dental agenesis at the second mandibular premolar positions (#35 and #45). Superimposition of the actual and simulated implants showed high concordance between them. CONCLUSION: AR in education offers crucial surgical information for novice surgeons in real time. However, the benefits provided by AR in clinical and educational implantology must be demonstrated in other studies involving a larger number of patients, surgeons and apprentices.

Engineering Precise Interconnected Porosity in ß-Tricalcium Phosphate (ß-TCP) Matrices by Means of Top-Down Digital Light Processing.

This study evaluated the biocompatibility and accuracy of 3D-printed ß-tricalcium phosphate (ß-TCP) pure ceramic scaffolds. A specific shaping process associating a digital light processing (DLP) 3D printer and a heat treatment was developed to produce pure ß-TCP scaffolds leaving no polymer binder residue. The ß-TCP was characterised using X-ray diffraction, infrared spectroscopy and the detection of pollutants. The open porosity of produced matrices and their resorption were studied by hydrostatic weighing and calcium release measures. The biocompatibility of the printed matrices was evaluated by mean of osteoblast cultures. Finally, macroporous cubic matrices were produced. They were scanned using a micro-Computed Tomography scanner (micro-CT scan) and compared to their numeric models. The results demonstrated that DLP 3D printing with heat treatment produces pure ß-TCP matrices with enhanced biocompatibility. They also demonstrated the printing accuracy of our technique, associating top-down DLP with the sintering of green parts. Thus, this production process is promising and will enable us to explore complex phosphocalcic matrices with a special focus on the development of a functional vascular network.

Epigenetic influence of KAT6B and HDAC4 in the development of skeletal malocclusion.

INTRODUCTION: Genetic influences on the development of malocclusion include heritable effects on both masticatory muscles and jaw skeletal morphology. Beyond genetic variations, however, the characteristics of muscle and bone are also influenced by epigenetic mechanisms that produce differences in gene expression. We studied 2 enzymes known to change gene expressions through histone modifications, chromatin-modifying histone acetyltransferase KAT6B and deacetylase HDAC4, to determine their associations with musculoskeletal variations in jaw deformation malocclusions. METHODS: Samples of masseter muscle were obtained from subjects undergoing orthognathic surgery from 6 malocclusion classes based on skeletal sagittal and vertical dysplasia. The muscles were characterized for fiber type properties by immunohistochemistry, and their total RNA was isolated for gene expression studies by microarray analysis and quantitative real-time polymerase chain reaction. RESULTS: Gene expressions for fast isoforms of myosins and contractile regulatory proteins and for KAT6B and HDAC4 were severalfold greater in masseter muscles from a patient with a deepbite compared with one with an open bite, and genes related to exercise and activity did not differ substantially. In the total population, expressions of HDAC4 (P = 0.03) and KAT6B (P = 0.004) were significantly greater in subjects with sagittal Class III than in Class II malocclusion, whereas HDAC4 tended to correlate negatively with slow myosin type I and positively with fast myosin gene, especially type IIX. CONCLUSIONS: These data support other published reports of epigenetic regulation in the determination of skeletal muscle fiber phenotypes and bone growth. Further investigations are needed to elucidate how this regulatory model might apply to musculoskeletal development and malocclusion.