Risk factors for the development of medication-related osteonecrosis of the jaw and effects of tooth extraction with local infection.

Background/purpose: Tooth extraction has been avoided in patients receiving antiresorptive agent (ARA) therapy. This study aimed to investigate dental findings associated with medication-related osteonecrosis of the jaw (MRONJ) development in patients. Materials and methods: First, in patients treated with high-dose ARAs, the relationship between dental findings and MRONJ development was examined. Next, in patients with MRONJ undergoing surgery, the relationship between dental findings and MRONJ occurring at a site distant from the initial site was examined. Results: MRONJ occurred in 13 of 172 patients (80 of 3725 teeth) during observation. Multiple tooth loss, periodontal ligament space enlargement, alveolar bone loss, periapical osteosclerosis, and local infection symptoms were associated with MRONJ development. Tooth extraction significantly reduced MRONJ development. Regarding other-site recurrence, new MRONJ developed at other sites in 54 of 357 patients with MRONJ (171 of 5038 teeth). Multiple tooth loss, apical lesions, periodontal ligament space enlargement, and periapical osteosclerosis were significantly associated with MRONJ development. In patients with malignant tumors, tooth extraction significantly reduced the subsequent incidence of MRONJ, while in patients with osteoporosis, there was no difference in the incidence of MRONJ between patients with and without tooth extraction. Conclusion: MRONJ was more likely to develop from teeth with local infections. Extraction of teeth with local infection in patients with malignancy may be more effective than tooth preservation in preventing MRONJ.

Bone resection methods in medication-related osteonecrosis of the jaw in the mandible: An investigation of 206 patients undergoing surgical treatment.

Background /purpose: The standard treatment for medication-related osteonecrosis of the jaw (MRONJ) is surgery. However, reports on the appropriate extent of bone resection are few. We aimed to examine the relationship between the extent of bone resection and postoperative outcomes in patients with mandibular MRONJ. Materials and methods: The clinical and imaging findings and treatment outcomes of 206 patients (258 surgeries) with mandibular MRONJ undergoing surgery were reviewed. Imaging findings were evaluated using computed tomography (CT) to sequestrum, osteolysis, periosteal reaction, and mixed-type osteosclerosis, and determine the extent of resection. In some cases, samples were taken from within the bone, and real-time polymerase chain reaction was used to confirm the presence of bacteria and fungi. Results: The three-year cumulative cure rate was 81.7%. Patients with malignant tumors showing no osteolysis and undergoing sequestrum removal or marginal mandibulectomy had significantly worse prognosis than those with osteoporosis showing osteolysis and undergoing segmental mandibulectomy. Furthermore, patients with residual osteolysis, periosteal reactions, and mixed-type osteosclerosis on CT were more likely to develop recurrence. Eleven patients showed no osteolysis on CT images. Patients with cancer administered with high-dose denosumab had significantly poorer prognosis. Bacteria and fungi were also detected in samples obtained from gap-type periosteal reaction and mixed-type osteosclerosis. Conclusion: Surgery for MRONJ requires resection of the infected bone. Aside from the osteolysis area, the gap-/irregular-type periosteal reaction and mixed-type osteosclerosis must also be included in the resection area. Methods for determining the extent of bone resection in MRONJ without osteolysis are a future challenge.

Differences Between Medication-Related Osteonecrosis of the Jaw Caused by Bisphosphonates and Denosumab: Histological, Molecular Biological, and Clinical Studies.

Purpose Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of antiresorptive agents such as bisphosphonates (BPs) and denosumab (DMB). We investigated whether a difference exists between BP- and DMB-related osteonecrosis of the jaw (ONJ). Patients and methods Histological images of 30 patients with BP-related ONJ and 13 patients with DMB-related ONJ were observed using hematoxylin-eosin and cathepsin K staining. Moreover, bone metabolism markers in the blood and bone mineral density were measured in 18 patients with BP-related ONJ and five patients with DMB-related ONJ. Furthermore, we conducted a quantitative analysis of local bone metabolism-related genes using surgical specimens through real-time reverse transcription polymerase chain reaction. Additionally, a retrospective study of 298 patients with MRONJ examined the differences in the characteristics of BP- and DMB-related ONJ and the factors associated with treatment outcomes. Results Histological examination revealed that patients treated with DMB had more severe osteoclast suppression than those treated with BP. No significant difference was observed in blood-bone metabolism markers between the two drugs; however, the suppression of local bone metabolism-related genes was stronger in patients treated with DMB. Clinical studies indicate that DMB-related ONJ is more frequently observed without osteolysis. Conclusion BP-associated ONJ and DMB-associated ONJ were shown to differ slightly. Clinical studies indicate that osteolysis is often unclear in DMB-related ONJ, and methods of bone resection during surgery need to be established.

Breath Measurement Method for Synchronized Reproduction of Biological Tones in an Augmented Reality Auscultation Training System.

An educational augmented reality auscultation system (EARS) is proposed to enhance the reality of auscultation training using a simulated patient. The conventional EARS cannot accurately reproduce breath sounds according to the breathing of a simulated patient because the system instructs the breathing rhythm. In this study, we propose breath measurement methods that can be integrated into the chest piece of a stethoscope. We investigate methods using the thoracic variations and frequency characteristics of breath sounds. An accelerometer, a magnetic sensor, a gyro sensor, a pressure sensor, and a microphone were selected as the sensors. For measurement with the magnetic sensor, we proposed a method by detecting the breathing waveform in terms of changes in the magnetic field accompanying the surface deformation of the stethoscope based on thoracic variations using a magnet. During breath sound measurement, the frequency spectra of the breath sounds acquired by the built-in microphone were calculated. The breathing waveforms were obtained from the difference in characteristics between the breath sounds during exhalation and inhalation. The result showed the average value of the correlation coefficient with the reference value reached 0.45, indicating the effectiveness of this method as a breath measurement method. And the evaluations suggest more accurate breathing waveforms can be obtained by selecting the measurement method according to breathing method and measurement point.

Extranodal Extension and Epithelial Cell Adhesion Molecule Over-expression in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Concomitant chemoradiotherapy (CCRT) with cisplatin is commonly administered after neck dissection in patients with oral squamous cell carcinoma (OSCC) showing extranodal extension (ENE). This study investigated whether the efficacy of CCRT differed depending on the degree of ENE and whether the expression of epithelial cell adhesion molecule (EpCAM) was associated with prognosis. PATIENTS AND METHODS: Patients with OSCC who underwent neck dissection and had histologically proven neck metastasis (pN+) were investigated retrospectively. ENE was divided into ENE minor (ENEmi; <2 mm) and ENE major (ENEma; ≥2 mm). The expression of EpCAM was also immunohistochemically examined using tissues obtained during neck dissection. RESULTS: One hundred and seventy pN+ cases [ENE(-), n=89; ENEmi, n=23; ENEma, n=58] were included. Multivariate analysis revealed that advanced T stage and ENEma were significantly correlated with poor prognosis. The 5-year disease-specific survival rates in ENE(-), ENEmi, and ENEma groups were 73.7%, 75.5%, and 28.0% respectively. An add-on effect of postoperative CCRT was not seen in the ENEmi group; however, postoperative CCRT improved the survival of patients in the ENEma group. In the ENEma group, the prognosis was significantly worse in EpCAM-positive patients than in EpCAM-negative patients. CONCLUSION: Postoperative CCRT may improve prognosis in ENEma cases. EpCAM expression may be a poor prognostic factor in ENEma cases. On the other hand, postoperative CCRT did not have a significant effect on prognosis in ENEmi cases. Among them, although there was no significant difference in the survival rate, postoperative CCRT could be omitted in ENEmi/EpCAM(-) cases.

A novel method for determining viable bacteria from a mixture of dead and viable bacteria: Delayed real-time PCR (DR-PCR) method.

Aspiration pneumonia can occur in perioperative and older patients, and various oral care methods have been used to prevent it. To validate the effective oral care methods, measuring bacterial counts before and after oral care is necessary. However, isolating and quantifying viable bacteria from those that are inactivated by agents used in oral care is not possible. In this study, we developed a novel method, Delayed real-time PCR (DR-PCR), that can quantify only viable bacteria from mixed samples of viable and dead bacteria. This method takes advantage of the fact that dead bacteria do not grow but viable bacteria do. When the samples were incubated in a liquid medium for 4 hours, the higher the percentage of viable bacteria, the higher the rate of increase in the number of bacteria. This method showed that povidone­iodine mouthwashing reduced the number of viable bacteria to approximately 1/4 of that before mouthwashing. Although DR-PCR is slightly more time consuming than real-time PCR, it is effective for studying changes in bacterial counts before and after oral care.

Swallowing Functions after Sagittal Split Ramus Osteotomy with Loose Fixation for Mandibular Prognathism: A Retrospective Case Series Research.

Sagittal split ramus osteotomy (SSRO) is a standard surgical technique for patients with mandibular prognathism. However, the appropriate position of the proximal fragment is not strictly defined, and rigid fixation can induce early postoperative skeletal relapse and temporomandibular (TMJ) disorders. Loose fixation can be expected to seat the proximal bone fragments in a physiologically appropriate position, thereby reducing adverse events. Although long-term skeletal stability has been achieved using SSRO without fixation, the evaluation of preoperative and postoperative eating and swallowing functions remains unclear, and this study aimed to clarify this point. We evaluated mastication time, oral transfer time, and pharyngeal transfer time using videofluorography (VF) preoperatively, two months postoperatively, and six months postoperatively, and along with the position of anatomical landmarks using cephalometric radiographs, modified water swallowing test (MWST), food test (FT), and repetitive saliva swallowing test (RSST) were used to evaluate postoperative swallowing function. Four patients (one male, three females; mean (range) age 26.5 (18-51) years) were included, with a mean setback of 9.5 mm and 6.5 mm on the right and left sides, respectively. Postoperative eating and swallowing functions were good in VF, cephalometric analysis, MWST, FT, and RSST. In the present study, good results for postoperative eating and swallowing functions were obtained in SSRO with loose fixation of the proximal and distal bone segments.

A Multicenter Study on the Effect of Margin Distance on Survival and Local Control in Stage 1-2 Squamous Cell Carcinoma of the Tongue.

BACKGROUND: Pathological close margins are considered a significant factor for local recurrence in patients with oral cancer. However, the oral cavity has complicated anatomical features, and the appropriate margin distance for each site is unknown. This multicenter, retrospective study aimed to determine the appropriate resection margin for early tongue cancer and investigate the need for additional treatment for close margins and stump dysplasia. PATIENTS AND METHODS: In total, 564 patients from ten hospitals were enrolled in this study. Sex, age, performance status, T stage, tumor length diameter, depth of invasion, elective neck dissection, iodine staining, horizontal margin distance, vertical margin distance, pathological differentiation, invasion pattern, lymphatic invasion, perineural invasion, dysplasia in the resection edge, additional treatment for close margins, local recurrence, neck metastasis, distant metastasis, and outcomes were investigated. RESULTS: Receiver operating characteristic analysis for local recurrence revealed cut-off values of 3.3 mm for horizontal distance and 3.1 mm for vertical distance. Patients with close horizontal or vertical margins showed significantly higher local recurrence rates, but these were not associated with overall or disease-specific survival. Furthermore, there was no effect of additional treatment in patients with dysplasia at the surgical margin. CONCLUSION: For early tongue cancer, a horizontal margin of 3.3 mm was defined as a close margin. Close margins were significantly correlated with local recurrence but did not affect survival. In the future, we would like to examine the concept of "quality margins," including the surrounding anatomical features.

Long-term clinical and radiographic evaluation after maxillary sinus floor augmentation with octacalcium phosphate-collagen composite: A retrospective case series study.

The purpose of this study was to evaluate, using clinical and radiological assessments, the stability of dental implants 5 years after maxillary sinus floor augmentation with octacalcium phosphate-collagen composite (OCP/Col). Maxillary sinus floor augmentation was performed through a lateral window approach. Depending on the height of the host bone, a simultaneous approach (≥5 mm) or a staged approach (less than 5 mm) was employed. The primary outcome was the evaluation of clinical dental implant conditions such as infection, peri-implantitis, dental implant stability, pain, and paresthesia. Secondary outcomes were the evaluation of the augmented bone volume, change rate of augmented bone volume, vertical bone height, and marginal bone loss around dental implant fixture. The conditions of all dental implants were uneventful throughout the follow-up period. Augmented bone volume and changing rate of augmented bone volume were essentially unchanged following maturation of the OCP/Col-derived new bone. The change rate of new bone volume was 21.9% in the simulated approach and 16.8% in the staged approach at 1 year and 5 years postoperatively. The reduction rate in vertical bone height was 7.1% in the simultaneous approach and 7.5% in the staged approach between 1 year and 5 years postoperatively. Mean marginal bone loss was 1.76 mm with the simultaneous approach, and 0.50 mm with the staged approach at 5 years postoperatively. In conclusion, the success of dental implants 5 years after sinus floor augmentation by OCP/Col implantation was clarified by both clinical and radiological evaluations.

Gene-activated matrix harboring a miR20a-expressing plasmid promotes rat cranial bone augmentation.

Gene-activated matrix (GAM) has a potential usefulness in bone engineering as an alternate strategy for the lasting release of osteogenic proteins but efficient methods to generate non-viral GAM remain to be established. In this study, we investigated whether an atelocollagen-based GAM containing naked-plasmid (p) DNAs encoding microRNA (miR) 20a, which may promote osteogenesis in vivo via multiple pathways associated with the osteogenic differentiation of mesenchymal stem/progenitor cells (MSCs), facilitates rat cranial bone augmentation. First, we confirmed the osteoblastic differentiation functions of generated pDNA encoding miR20a (pmiR20a) in vitro, and its transfection regulated the expression of several of target genes, such as Bambi1 and PPARγ, in rat bone marrow MSCs and induced the increased expression of BMP4. Then, when GAMs fabricated by mixing 100 µl of 2% bovine atelocollagen, 20 mg ß-TCP granules and 0.5 mg (3.3 µg/µl) AcGFP plasmid-vectors encoding miR20a were transplanted to rat cranial bone surface, the promoted vertical bone augmentation was clearly recognized up to 8 weeks after transplantation, as were upregulation of VEGFs and BMP4 expressions at the early stages of transplantation. Thus, GAM-based miR delivery may provide an alternative non-viral approach by improving transgene efficacy via a small sequence that can regulate the multiple pathways.

Movement of the proximal segment after intraoral vertical ramus osteotomy versus short lingual osteotomy with physiological positioning strategy.

PURPOSE: To clarify whether intraoral vertical ramus osteotomy (IVRO) or short lingual osteotomy (SLO) induces less proximal segmental movement after surgery without bone fixation. METHODS: This study included patients who underwent IVRO or SLO without bone fixation. Cephalograms were taken before surgery (T1), immediately after surgery (T2), and >6 months after surgery (T3) to assess postoperative movement of the proximal segment and skeletal stability. The condylar angle was measured using computed tomography images taken at T1 and T3 to assess rotation. RESULTS: Ninety patients were included (IVRO, n = 25; SLO, n = 65). The proximal segment swung laterally on the frontal cephalogram in the asymmetrical IVRO group at T3. The condylar head was rotated outwardly 6.52 ± 4.49° (p < 0.0001) in the symmetrical IVRO group and 8.06 ± 6.88° (p = 0.030) on the non-deviated side in the asymmetrical IVRO group at T3. The condyles were almost stable in the SLO group. Temporomandibular joint disorders were found in 2 of 22 IVRO patients and in 2 of 42 SLO patients with asymmetry at T3. CONCLUSION: This study suggests that SLO with the physiological positioning strategy (PPS) should be preferred over IVRO with the PPS whenever possible.

Clinical study of octacalcium phosphate and collagen composite in oral and maxillofacial surgery.

Octacalcium phosphate and its collagen composite have been recognized as bone substitute materials possessing osteoconductivity and biodegradation properties. We evaluated the effectiveness of octacalcium phosphate and its collagen composite used for bone augmentation in major oral and maxillofacial surgeries in a clinical trial. Octacalcium phosphate and its collagen composite were used in cases of sinus floor elevation in 1- and 2-stage, socket preservation, cyst, and alveolar cleft procedures. A total of 60 patients were evaluated for effectiveness after the implantation of octacalcium phosphate and its collagen composite. Although sinus floor elevation in 1-stage, cyst, and alveolar cleft cases met the criteria for the judgment of success, sinus floor elevation in 2-stage and socket preservation groups did not meet the criteria in the initial evaluation. However, an additional evaluation for reconfirmation revealed the effectiveness of octacalcium phosphate and its collagen composite in those groups, and all evaluation results ultimately indicated the success of this clinical trial. Therefore, this clinical trial suggested that application of octacalcium phosphate and its collagen composite for oral and maxillofacial surgery was safe and effective and that octacalcium phosphate and its collagen composite could be a bone substitute candidate instead of autologous bone.

First clinical application of octacalcium phosphate collagen composite on bone regeneration in maxillary sinus floor augmentation: A prospective, single-arm, open-label clinical trial.

The overall objective of this study was to assess the safety and efficacy of OCP/Col as a bone substitute material for bone regeneration during sinus floor augmentation. Maxillary sinus floor augmentation was performed thorough lateral window approach. According to the height of host bone, simultaneous approach (≥5 mm) or staged approach (less than 5 mm) was applied. In this research, clinical findings of dental implant treatment after setting the restorations were set as a primary endpoint in both approaches (infection, inflammation around the implant, movement of the implant, pain, sensory disorder, and bone resorption around the implant body on radiological evaluation.). In staged approach, histological evaluation of bone biopsy specimen was also conducted. As secondary endpoints, hounsfield unit (HU) value, vertical bone height, implant stability quotient (ISQ), and adverse events during the research were evaluated. In all cases, as a primary endpoint, clinical findings after setting the restorations were uneventful with no adverse events. Histological structure demonstrated mature bone derived from OCP/Col. In the ossified area, osteogenesis was observed around OCP granules, and osteoblast-like cells were arrayed around OCP granules. Osteocyte encapsulation was recognized in the new bone. HU increased over time with both approaches. Vertical bone height significantly increased at 3 months postoperatively, and maintained during follow-up. ISQ increased with both approaches. In particular, ISQ was significantly increased with the staged approach. This clinical trial demonstrated the safety and efficacy of OCP/Col for bone regeneration in maxillary sinus floor augmentation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:243-252, 2020.

Very early tissue coverage after drug-eluting stent implantation: an optical coherence tomography study.

The aim of this study was to evaluate neointimal coverage in the very early phase after second-generation drug-eluting stent (DES) implantation using optical coherence tomography (OCT). Patients who underwent staged percutaneous coronary intervention within 30 days after DES implantation were enrolled. OCT was performed to observe DES previously implanted. The median time interval from implantation to OCT examination was 21.5 days. A total of 10,625 struts of 54 stents (52 everolimus-eluting stents and 2 zotarolimus-eluting stents) in 42 lesions were analyzed. Strut tissue coverage was observed in 71.1 ± 19.2 % of the struts, malapposed struts in 2.56 ± 3.37 %, strut tissue coverage at the side branch orifice in 10.6 ± 17.2 %, and struts with protrusion in 0.95 ± 3.46 %. Mean tissue thickness on the covered struts was 39.8 ± 14.2 µm. The percentage of stent coverage was significantly lower in the overlapping segments than in the non-overlapping segments (48.4 ± 17.5 % vs. 74.4 ± 20.2 %, P < 0.05). Most of the stent struts were covered by tissue within 30 days after second-generation DES implantation. However, the percentage of strut coverage was lower in the overlapping segments than in the non-overlapping segments, suggesting that very early interruption of dual antiplatelet therapy might result in increased risk of stent thrombosis, even in second-generation DES.

Skeletal stability after sagittal split ramus osteotomy with physiological positioning in patients with skeletal mandibular prognathism and facial asymmetry.

The correction of deformities of the jaw in patients with facial asymmetry is challenging because of the high rate of relapse, which may partly be caused by skeletal interference and inappropriate seating of the condylar head. We evaluated outcomes in 30 patients who were treated by short lingual osteotomy with physiological positioning. Nine had facial symmetry (absolute displacement of the menton<2mm), 14 had minor asymmetry (displacement of >2 to <4mm), and 7 severe asymmetry (displacement of >4mm). The postoperative position of the menton (Me) was stable in each group, but deviated by 3.56mm in those with severe asymmetry. This deviation remained immediately after operation and after more than one year in this group, which implies that the Me was not on the mandibular midline. The lateral swing of both sides of the proximal segment did not change immediately after operation in any group. Although short lingual osteotomy with physiological positioning can result in skeletal stability, it is important to assess the association between the dental arch and the mandible using computed tomography to ensure a good outcome in patients with a skeletal class III deformity and facial asymmetry.

Sonographic Evaluation of Bone Formation After Sagittal Split Ramus Osteotomy.

OBJECTIVES: The aim of this study was to assess the applicability of sonography for evaluation of mandible bone healing after orthognathic surgery. METHODS: The study included 10 patients who underwent orthognathic surgery. To assess new bone formation after sagittal split ramus osteotomy, the echo intensities of ultrasound (US) reflections of the proximal segment, distal segment, and bone gap were measured with a real-time US scanner at 1 day, 1, 2, 3, and 4 weeks, and 2 and 4 months postoperatively. RESULTS: The mean echo intensity of US reflections of the bone gap gradually increased and became equivalent to that of bone surfaces by 4 weeks postoperatively. X-ray tomograms confirmed bone formation at the bone gap at the same time. CONCLUSIONS: This study indicates that sonography may be useful for evaluating osseous healing after orthognathic surgery.

Bone Regeneration Using Dentin Matrix Depends on the Degree of Demineralization and Particle Size.

OBJECTIVES: This study aimed to examine the influence of particle size and extent of demineralization of dentin matrix on bone regeneration. MATERIALS AND METHODS: Extracted human teeth were pulverized and divided into 3 groups according to particle size; 200, 500, and 1000 µm. Each group was divided into 3 groups depending on the extent of demineralization; undemineralized dentin (UDD), partially demineralized dentin matrix (PDDM), and completely demineralized dentin matrix (CDDM). The dentin sample was implanted into rat calvarial bone defects. After 4 and 8 weeks, the bone regeneration was evaluated with micro-CT images, histomorphometric and immunohistochemical analyses. Osteoblasts were cultured on UDD and DDM to evaluate the cell attachment using electron microscope. RESULTS: Micro-CT images and histological observation revealed that CDDM had largely resorbed but UDD had not, and both of them induced little bone formation, whereas all particle sizes of PDDM induced more new bone, especially the 1000 µm. Electron microscopic observation showed osteoblasts attached to DDM but not to UDD. CONCLUSIONS: PDDM with larger particle size induced prominent bone regeneration, probably because PDDM possessed a suitable surface for cell attachment. There might be an exquisite balance between its resorption and bone formation on it. PDDM could be considered as a potential bone substitute.