Evaluating Morphology of the Pterygomaxillary Junction and Its Association With the Orbit in Different Facial Skeletal Relationships.

PURPOSE: The etiology for blindness after Le Fort I osteotomy is poorly understood. The authors propose that a study of the morphology and anatomical relationship of the pterygomaxillary junction to orbital vital structures may be crucial for understanding the possible etiology. MATERIALS AND METHODS: This retrospective observational study involved analysis of data procured from computed tomography scans of individuals who were categorized into 4 groups based on their skeletal characteristics: skeletal Class I, II, and III and cleft lip and palate (CLP). The outcome variables included i) the height, width, and thickness of the pterygomaxillary junction (PTMJ) which represent its morphology and ii) distance of the PTMJ to the superior orbital fissure and optic canal, to demonstrate its proximity to orbital vital structures. Primary outcome measures were to i) compare variance of the outcome variables across groups, ii) determine association between PTMJ morphology and its proximity to the orbit, and iii) determine association between skeletal morphology and the outcome variables. Data were analyzed using descriptive and inferential statistics to study variance and association. RESULTS: Forty patients (80 sides) were divided into 4 groups. The CLP group demonstrated maximum height and thickness of the PTMJ, whereas the Class II group demonstrated the minimum (P < .001 and P = .001, respectively). The CLP group demonstrated the closest proximity of the PTMJ to orbital vital structures (P < .001), with Class II being the farthest (P < .001). There was a weak positive correlation between the PTMJ height and its thickness and width, whereas a moderate negative correlation was seen between the PTMJ height and its distance from the optic canal and superior orbital fissures (P < .001). CONCLUSIONS: Morphology of the PTMJ varies with facial skeletal relationship and also influences the relationship of the PTMJ with the orbital vital structures. This may be critical in understanding the pathophysiology of blindness after Le Fort I osteotomies.

Three-Dimensional Geometric Morphometry of Facial Soft Tissue Changes After Bilateral Sagittal Split Ramus Osteotomy.

ABSTRACT: This study aimed to evaluate the performance of geometric morphometry (GM) to assess the changes in facial soft tissue after orthognathic surgery. Subjects were 27 patients (skeletal class III) who underwent bilateral sagittal split ramus osteotomy and 27 volunteers as a control group. Computed tomography images of each patient were obtained before surgery (T0) and 6 months after surgery (T1). Computed tomography images of 27 volunteers (skeletal class I) were also obtained as a control group. Using a three-dimensional (3D) modeling software, 3D models were created and exported to a 3D surface analyzing software for geometric morphometry and principal component (PC) analysis. Significant differences in facial soft tissue were found in the first and second of 15 PC. The first PC represented variation in the lower facial height, and the second PC represented variation in the anterior-posterior position of the chin. Comparing the pre- and post-operative images, they illustrated that lower facial height was decreased, and the chin and lower lip moved posteriorly. Geometric morphometry showed to be a successful tool to isolate surgery-related changes from interindividual morphological variations.

Bone morphogenetic protein induces bone invasion of melanoma by epithelial-mesenchymal transition via the Smad1/5 signaling pathway.

Oral malignant melanoma, which frequently invades the hard palate or maxillary bone, is extremely rare and has a poor prognosis. Bone morphogenetic protein (BMP) is abundantly expressed in bone matrix and is highly expressed in malignant melanoma, inducing an aggressive phenotype. We examined the role of BMP signaling in the acquisition of an aggressive phenotype in melanoma cells in vitro and in vivo. In five cases, immunohistochemistry indicated the phosphorylation of Smad1/5 (p-Smad1/5) in the nuclei of melanoma cells. In the B16 mouse and A2058 human melanoma cell lines, BMP2, BMP4, or BMP7 induces morphological changes accompanied by the downregulation of E-cadherin, and the upregulation of N-cadherin and Snail, markers of epithelial-mesenchymal transition (EMT). BMP2 also stimulates cell invasion by increasing matrix metalloproteinase activity in B16 cells. These effects were canceled by the addition of LDN193189, a specific inhibitor of Smad1/5 signaling. In vivo, the injection of B16 cells expressing constitutively activated ALK3 enhanced zygoma destruction in comparison to empty B16 cells by increasing osteoclast numbers. These results suggest that the activation of BMP signaling induces EMT, thus driving the acquisition of an aggressive phenotype in malignant melanoma.

Characteristics of craniofacial morphology and factors affecting them in patients with isolated cleft palate.

BACKGROUND: Myriad maxillo-mandibular occlusal relationships are observed in patients with isolated cleft palate (ICP), unlike in patients with other cleft types, such as cleft lip and palate. OBJECTIVES: This study aimed to categorise the characteristics of craniofacial morphology in patients with ICP, and investigate the clinical factors affecting these categorised morphological characteristics. METHODS: Thirty-six girls with ICP (age (mean ± SD): 5.36 ± 0.36 years) underwent cephalometric measurement. Their craniofacial morphology was categorised using cluster analysis. Profilograms were created and superimposed onto the standard Japanese profilograms to visualise the morphological characteristics of each group (cluster). The mean values and variations in the linear and angular measurements of each group were compared with the Japanese standards and statistically analysed using Dunnett's test after the analysis of variance. Fisher's exact test was used to analyse the differences between the cleft types (cleft in the hard and/or soft palate) and skills of the operating surgeons in the groups. RESULTS: Cluster analysis of craniofacial morphologies in patients with ICP resulted in the formation of three categories: the first cluster exhibited a relatively harmonious anteroposterior relationship between the maxilla and the mandible (22.2%); the second cluster exhibited crossbite owing to a significantly smaller maxilla (33.3%); and the third cluster exhibited a smaller mandible with posterior rotation showing skeletal class II malocclusion (44.4%). Differences in cleft types and surgeons were not associated with the distribution of patients in each cluster. CONCLUSIONS: Patients with ICP exhibited characteristic morphological patterns, such as bimaxillary retrusion or severe mandibular retrusion, besides the anterior crossbite frequently found in patients with cleft lip and palate . Understanding the typical morphological characteristics could enable better diagnostic categorisation of patients with ICP, which may eventually improve orthodontic treatment planning.

Regulation of NF-kB Signalling Through the PR55ß-RelA Interaction in Osteoblasts.

BACKGROUND/AIM: Nuclear factor kappa B (NF-kB) signalling including the RelA subunit is activated upon fibroblast growth factor (FGF) stimulation. A clear understanding of the mechanisms underlying this action will provide insights into molecular targeting therapy. Furthermore, protein phosphatase 2A (PP2A) is involved in RelA dephosphorylation, but little is known about the underlying mechanism. MATERIALS AND METHODS: Because the regulatory subunits of PP2A drive NF-kB signalling via RelA, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in MC3T3-E1 cells. We examined weather FGF2 interacts with NF-kB using immunocytochemistry (IC), immunoprecipitation (IP), and pull-down assay (PD) using recombinant proteins. RESULTS: PR55ß expression was increased, whereas activated RelA was dephosphorylated upon FGF2 stimulation. Further, the interaction of PR55ß with RelA was confirmed by IC, IP, and PD. CONCLUSION: FGF2-induced PR55ß directly interacts with RelA and regulates NF-kB signalling.

Masticatory muscle function affects the pathological conditions of dentofacial deformities.

The causes of dentofacial deformities include various known syndromes, genetics, environmental and neuromuscular factors, trauma, and tumors. Above all, the functional effects of muscles are important, and deformation of the mandible is often associated with a mechanical imbalance of the masticatory muscles. With the vertical position of the face, weakness of the sling of the masseter muscle and medial pterygoid muscle causes dilatation of the mandibular angle. In patients with a deep bite, excessive function of the masticatory muscles is reported. Myosin heavy chain　(MyHC) properties also affect jawbone morphology. In short-face patients, the proportion of type II fibers, which are fast muscles, is high. The proportions of muscle fiber types are genetically determined but can be altered by postnatal environmental factors. Orthognathic surgery may results in the transition of MyHC to type II (fast) fibers, but excessive stretching enhances the release of inflammatory mediators and causes a shift toward a greater proportion of slow muscle fibers. This feature can be related to postoperative relapse. Bones and muscles are in close crosstalk, and it may be possible to use biochemical approaches as well as biomechanical considerations for the treatment of jaw deformities.

Lower Lip Cancer Managed by Reconstruction with a Double Abbe Flap - A Case Report.

Although the incidence of lower lip cancer is not high in Japan, its treatment requires an approach that considers both esthetics and function. When surgical resection is required, the method used for reconstruction varies depending on the affected part. Despite various studies proposing different types of algorithms, no single method is considered the best. If the loss of half or more of the lip is predicted, a free flap may need to be considered, depending on the case. Here, we report a case involving a 78-year-old edentulous woman with lower lip cancer whose resection area involved approximately 70% of the red and white portions of the lower lip. Fortunately, no resection was required at the commissure. We accordingly performed reconstruction with a double Abbe flap in accordance with a detailed treatment plan. The patient was extremely satisfied with the esthetic and functional outcomes of the surgery.

Identifying Differences Between a Straight Face and a Posed Smile Using the Homologous Modeling Technique and the Principal Component Analysis.

Recently, a homologous modeling method was developed to simulate 3D human body forms, which can visualize principal component analysis (PCA) results and facilitate its detailed comparison with results of previous method. Herein, we aimed to construct a homologous model of the face to identify differences between a straight face and a posed smile. Thirty-eight volunteers (19 males and 19 females, 38 straight faces and 38 posed smiles) with no medical history associated with a posed smile were enrolled. Three-dimensional images were constructed using the Homologous Body Modeling software and the HBM-Rugle; 9 landmarks were identified on the 3D-model surfaces. The template model automatically fitted into an individually scanned point cloud of the face by minimizing external and internal energy functions. Faces were analyzed using PCA; differences between straight faces and posed smiles were analyzed using paired t tests. Contribution of the most important principal component was 23.8%; 8 principal components explained >75% of the total variance. A significant difference between a straight face and a posed smile was observed in the second and the fourth principal components. The second principal component images revealed differences between a straight face and a posed smile and changes around the chin area with regard to length, shape, and anteroposterior position. Such changes were inclusive of individual differences. However, the fourth principal component image only revealed differences between a straight face and a posed smile; observed differences included simultaneous shortening of upper and lower eyelid length, evaluation of the nasal ala ase, swelling of the cheek area, and elevation of the mouth angle. Although these results were clinically apparent, we believe that this article is the first to statistically verify the same.Consequently, the homologous model technique and PCA are useful for evaluation of the facial soft-tissue changes.

Extracellular calcium stimulates osteogenic differentiation of human adipose-derived stem cells by enhancing bone morphogenetic protein-2 expression.

Bone morphogenetic protein-2 (BMP-2) promotes the differentiation of non-osteogenic mesenchymal cells to osteogenic cells. In this study, we isolated human adipose-derived stem cells (hASCs) and investigated the effects of recombinant human BMP-2 (rhBMP-2) and extracellular Ca2+ concentration ([Ca2+]out) on the osteogenic differentiation of hASCs. rhBMP-2 promoted calcium deposition in hASCs and stimulated the mRNA expressions of six proteins known to be involved in the osteogenic differentiation of hASCs: Runx2, osterix, alkaline phosphatase, osteonectin, bone sialoprotein and osteocalcin. Elevation of [Ca2+]out enhanced the level of alkaline phosphatase enzyme, increased the mRNA expressions of Runx2 and osteocalcin and induced the expressions of BMP-2 mRNA and protein in hASCs. Elevation of [Ca2+]out transiently increased the intracellular Ca2+ concentration ([Ca2+]in) due to activation of the calcium-sensing receptor (CaSR). The Ca2+-induced expressions of BMP-2 mRNA and protein were inhibited by the calmodulin antagonist, W-7. Furthermore, elevation of [Ca2+]out decreased the cytoplasmic level of phosphorylated nuclear factor of activated T-cell-2 (NFAT-2) and increased the nuclear level of dephosphorylated NFAT2. Taken together, these results suggest that rhBMP-2 promotes the osteogenic differentiation of hASCs. Furthermore, an increase in [Ca2+]out enhances the expression of BMP-2 via activation of the CaSR, elevation of [Ca2+]in and stimulation of Ca2+/calmodulin-dependent NFAT-signaling pathways.

Beckwith-Wiedemann syndrome with asymmetric mosaic of paternal disomy causing hemihyperplasia.

Beckwith-Wiedemann syndrome (BWS) is a congenital disorder with 3 main features-overgrowth in infancy, macroglossia, and abdominal wall defects. Here, we report on a 5-month old girl with hemihyperplasia and macroglossia caused by paternal uniparental disomy (pUPD) asymmetric mosaic on chromosome 11p15.5. She could not retract her tongue into her mouth and the midline of the tongue was shifted to the left. Glossectomy was performed at age 1 year. A specimen of the tongue showed normal skeletal muscle, but the muscle fibers were closely spaced, and there were fewer stroma components in the tissue from the right side of the tongue than that from the left side. With respect to pUPD of chromosome 11p15.5, microsatellite marker analysis of the tongue tissue specimen revealed a higher mosaic rate in the tissue from the right side of the tongue (average 48.3%) than that from the left side (average 16.9%). Methylation analysis of Kv differentially methylated region (DMR) 1 (KvDMR1) and H19DMR revealed hypomethylation of KvDMR1 and hypermethylation of H19DMR in the tissue on the right side of the tongue (hyperplastic side). In this case, the difference in mosaic rate of pUPD in the 11p15.5 region was hypothesized to influence the expression level of insulin-like growth factor 2. This result may be helpful to clinicians, especially surgeons, when planning plastic surgery for hemihyperplasia.

Surface plasma treatment and phosphorylation enhance the biological performance of poly(ether ether ketone).

Poly(ether ether ketone) (PEEK) has emerged as an alternative endosseous material to metal implants mainly because of its lack of allergic sensitivity and radiolucency, while maintaining similar mechanical properties with bone. However, a disadvantage of PEEK is its weak osseointegration ability compared with metal implants. To overcome this, we prepared a phosphate group-modified PEEK by plasma treatment and subsequent phosphorylation reaction. Plasma treatment and phosphate modification of PEEK changed its hydrophobic surface to a hydrophilic surface while maintaining the original surface topography and roughness. Phosphate modification increased the bioactivity of rat bone marrow stromal cells (BMSCs), including proliferation, alkaline phosphatase activity, and bone-like nodule formation; however, this effect was negligible in plasma-treated PEEK. In addition, phosphate modification attenuated the phenotypic polarization of lipopolysaccharide-primed RAW264.7 macrophages to an inflammatory phenotype, based on the finding that macrophages on phosphate-modified PEEK produced decreased levels of the inflammatory cytokine and increased levels of the anti-inflammatory cytokine. Finally, in an animal study, phosphate-modified PEEK exhibited a doubled pullout force from the femur bone cavity compared with bare PEEK. Thus, we conclude that phosphate modification can significantly improves the implant-bone bonding strength of PEEK by enhancing BMSCs activity and reducing excessive inflammation.

Synergistic effect of surface phosphorylation and micro-roughness on enhanced osseointegration ability of poly(ether ether ketone) in the rabbit tibia.

This study was aimed to investigate the osseointegration ability of poly(ether ether ketone) (PEEK) implants with modified surface roughness and/or surface chemistry. The roughened surface was prepared by a sandblast method, and the phosphate groups on the substrates were modified by a two-step chemical reaction. The in vitro osteogenic activity of rat mesenchymal stem cells (MSCs) on the developed substrates was assessed by measuring cell proliferation, alkaline phosphatase activity, osteocalcin expression, and bone-like nodule formation. Surface roughening alone did not improve MSC responses. However, phosphorylation of smooth substrates increased cell responses, which were further elevated in combination with surface roughening. Moreover, in a rabbit tibia implantation model, this combined surface modification significantly enhanced the bone-to-implant contact ratio and corresponding bone-to-implant bonding strength at 4 and 8 weeks post-implantation, whereas modification of surface roughness or surface chemistry alone did not. This study demonstrates that combination of surface roughness and chemical modification on PEEK significantly promotes cell responses and osseointegration ability in a synergistic manner both in vitro and in vivo. Therefore, this is a simple and promising technique for improving the poor osseointegration ability of PEEK-based orthopedic/dental implants.

Osteosynthesis Using the Uncalcined and Unsintered Hydroxyapatite / Poly-L-Lactic Acid System.

The poly-L-lactic acid mini-plate system accomplished rapid development. However, the system still has a variety of problems. One such problem is the breakage of screws. In this technical report, we develop the temporary fixing screws made from stainless with hexagon steel that exhibit a hexagonal head and thread part that also features a tapping function.

Three-dimensional titanium miniplates for fixation of subcondylar mandibular fractures: Comparison of five designs using patient-specific finite element analysis.

PURPOSE: The purpose of the current study is to compare the performance of five designs of three-dimensional titanium miniplates (lambda, strut, delta, rhombic and trapezoid) for fixation of subcondylar mandibular fracture. MATERIALS AND METHODS: Three-dimensional models were constructed for the five miniplates with their screws and integrated into a virtually fractured mandible that was derived from a computed tomographic image of living human. Patient-specific finite element models were analyzed to compare the performances of the miniplates. Miniplates were compared for titanium hardware volume, condylar head displacement, bone strains and miniplates' stresses. RESULTS: Least condylar head displacement, and thereby best fixation primary stability, was found in the trapezoid miniplate. On the other hand, the greatest displacements were found in lambda and strut miniplates. Bone strains, as an indicator of secondary stability, predicted high strains in bone around the screws affixing the delta miniplate. Therefore, high risk of failure due to screws loosening is expected when using the delta miniplate. Stresses in miniplates were excessive in the strut and lambda miniplates, which implies a high risk of miniplate fracture. CONCLUSIONS: The current findings predicted significant differences in performance among the different designs of three-dimensional miniplates. The trapezoid miniplate seems to have the best performance, as it provided the greatest rigidity with relatively low bone strains.

Mandibular central leiomyosarcoma with high telomerase activity: a case report.

Leiomyosarcoma is a malignant lesion of smooth muscle origin, and rare in the oral region. This report presents an extremely rare case of intraosseous leiomyosarcoma of the mandible. After visiting other general hospital, a 29-year-old man was referred to our hospital because of a pain in the left mandibular region with paresthesia of the left mental region. The left mandibular third molar had already been extracted in another hospital, and a brownish mass occupied the corresponding region. A panoramic radiograph showed osteolytic destruction around the left mandibular angle and ramus. A computed tomography scan and magnetic resonance image revealed perforation of the lingual and buccal cortex of the mandible. A non-epithelial malignant tumor was diagnosed from a biopsy specimen. Immediately, we resected the tumor and reconstructed the titan plate under general anesthesia. A final diagnosis of leiomyosarcoma was made from a surgical specimen based on findings showing a proliferation of hyperchromatic spindle cells, which were positive for the markers α- smooth muscle actin, calponin, HHF35, and desmin. The S-100, epithelial membrane antigen, and cytokeratin markers were negative. The patient had 3 courses of adjuvant chemotherapy after the operation, and showed no evidence of recurrence during the follow-up at the outpatient clinic. However, 2 years after the first operation, lung metastases and local recurrence were detected. Additional chemotherapy was not effective. Finally, the patient died almost 3 years after the first operation.

Regulation of ß-Catenin Phosphorylation by PR55ß in Adenoid Cystic Carcinoma.

BACKGROUND/AIM: Adenoid cystic carcinoma (AdCC) is a rare cancer of the salivary gland with high risk of recurrence and metastasis. Wnt signalling is critical for determining tumor grade in AdCC, as it regulates invasion and migration. ß-catenin dephosphorylation plays an important role in the Wnt pathway, but its underlying molecular mechanism remains unclear. MATERIALS AND METHODS: Because the regulatory subunits of protein phosphatase 2A (PP2A) drive Wnt signalling via target molecules, including ß-catenin, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in an AdCC cell line (ACCS) and a more aggressive subline (ACCS-M). RESULTS: PR55ß was highly expressed in ACCS-M, suggesting its functional importance. In addition, PR55ß expression was associated with tumor grade, with ACCS-M exhibiting higher PR55ß levels. More importantly, knockdown of PR55ß in ACCS-M cells significantly reduced invasiveness and metastatic ability. Furthermore, dephosphorylation and total levels of ß-catenin were dependent on PR55ß in ACCS-M. Finally, we confirmed a correlation between PR55ß staining intensity and histopathological type in human AdCC tissues. CONCLUSION: Our study provides new insight into the interaction between PR55ß and ß-catenin and suggests that PR55ß may be a target for the clinical treatment of AdCC.

Deregulation of Nicotinamide N-Methyltransferase and Gap Junction Protein Alpha-1 Causes Metastasis in Adenoid Cystic Carcinoma.

BACKGROUND/AIM: Adenoid cystic carcinoma (AdCC) is a malignant tumor that occurs in the salivary glands and frequently metastasizes. The aim of this study was to identify factors mediating AdCC metastasis. MATERIALS AND METHODS: We established three AdCC cell lines by orthotropic transplantation and in vivo selection: parental, highly metastatic (ACCS-M-GFP), and lymph node metastatic (ACCS-LN-GFP) cells. RESULTS: We examined the three cell lines. DNA microarray indicated significantly altered processes in ACCS-LN-GFP cells: particularly, the expression of nicotinamide N-methyltransferase (NNMT) was enhanced the most. NNMT is associated with tumorigenesis and is a potential tumor biomarker. Concomitantly, we found-significant down-regulation of gap junction protein alpha-1. We suggest that ACCS-LN-GFP cells acquire cancer stem cell features involving the up-regulation of NNMT and the loss of gap junction protein alpha-1, leading to epithelial-mesenchymal transition and consequent AdCC metastasis. CONCLUSION: NNMT is a potential biomarker of AdCC.

Preoperative chronic sinusitis as significant cause of postoperative infection and implant loss after sinus augmentation from a lateral approach.

OBJECTIVES: Among intra/postoperative complications of sinus augmentation from a lateral approach, postoperative infection and implant loss are particularly important because they have irreversible consequences. The purpose of this study was to determine the causes of postoperative infection and implant loss after a lateral approach and to determine the appropriate prophylaxis and therapy. MATERIALS AND METHODS: In total, 109 patients (121 sinuses, 252 implants) were included in this study. The correlation between postoperative infection and implant loss and clinical variables was assessed using logistic regression analyses. RESULTS: Postoperative infection and implant loss occurred in 8/121 sinuses (6.6%). Infection had the strongest correlation to preoperative chronic sinusitis (p = 0.007), followed by timing of implant insertion. Implant loss had the strongest correlation to preoperative chronic sinusitis (p = 0.007), followed by sex, diabetes, postoperative use of dentures, and intraoperative perforation of the sinus membrane. CONCLUSIONS: Preoperative chronic sinusitis could be a significant cause of postoperative infection and implant loss when using sinus augmentation from a lateral approach. For appropriate prophylaxis and therapy, it is necessary to diagnose the presence of chronic sinusitis that should be treated with proper methods prior to sinus augmentation.

The relationship between lateral displacement of the mandible and scoliosis.

OBJECTIVES: Idiopathic scoliosis is an orthopaedic disease of childhood, with onset and progress occurring until adolescence. Here, the relationship between lateral displacement of the mandible and scoliosis was analysed quantitatively. METHODS: Seventy-nine non-syndromic Japanese patients (18 men, 61 women), who were diagnosed with jaw deformities and underwent surgical orthognathic treatment at Kyushu University Hospital from January 2011 to August 2014, were enrolled. Their mean age at the time of radiography was 25.3 ± 8.7 years. Postero-anterior cephalometric radiographs and chest radiographs were examined. In postero-anterior cephalometric radiographs, a horizontal baseline (X-axis) was drawn as a straight line that intersects both the zygomatic bases, and a vertical line (Y-axis) was marked perpendicular to the X-axis, with an intersection at the anterior nasal spine (ANS). Point A was defined as the intersection of the X- and Y-axes, and line A was defined as the line connecting point A to the menton. The angle made by the X-axis and line A (i.e., lateral displacement of the mandible) was measured. We designated an absolute value even if the mandibular menton was located on the right or left side. In chest radiographs, Cobb's method was used to measure scoliosis curves; the direction of the curve was designated similarly. RESULTS: Nine (11.4%) individuals had a Cobb angle >10°. There was a positive correlation between the Cobb angle and the degree of mandibular deviation (p < 0.05). CONCLUSION: Lateral displacement of the mandible and scoliosis are related.

Primary wound closure after tooth extraction for prevention of medication-related osteonecrosis of the jaw in patients under denosumab.

OBJECTIVES: Some recent reports have indicated that local infection causes osteonecrosis of the jaw and described that tooth extraction may not be a direct cause of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive medications. Tooth extraction and elimination of the source of infection are expected to reduce the risk of developing MRONJ. However, there is no data regarding prevention for developing osteonecrosis of the jaw in patients receiving denosumab. Therefore, the aim of this study was to investigate the outcome of tooth extractions with proper wound closure in patients receiving denosumab. PATIENTS AND METHODS: Forty teeth in 19 patients treated with denosumab therapy were extracted under preoperative intravenous antibiotics. Patients who had already developed MRONJ in the extraction sites or who had a history of radiation therapy were excluded. During surgery, bone edges were smoothed and all wounds were closed using the double-layered technique. RESULTS: Thirty-seven extraction sites (92.5 %) in 17 out of 19 patients (89.5 %) were healed. However, three extraction sites in two patients had complications; one patient had exposed bone and developed MRONJ (stage 1) and the other developed a mucosa fistula. Additional surgical procedures were performed and all wounds were completely healed. CONCLUSIONS: Tooth extractions in patients receiving denosumab can be performed in an appropriate manner and result in good outcomes. CLINICAL RELEVANCE: This study indicated that tooth extraction with proper wound closure to avoid secondary infection may be effective for the prevention of MRONJ even in high-risk patients.