Assessment of Patient Characteristics Influencing the Analgesic Effects of Ibuprofen Gargle After Mandibular Third Molar Extractions.

Introduction In our previous work, we investigated the analgesic effects of ibuprofen gargle after mandibular third molar extractions. However, a subsequent detailed review of individual patient data revealed variations in postoperative pain reduction among patients. Consequently, the present study was designed to conduct post-hoc subanalyses that identified factors contributing to variation in the analgesic response to ibuprofen gargle after third molar extractions. Materials and methods This study involved thirty-five Japanese patients from a prior randomized, double-blind, placebo-controlled, crossover study, which focused on the analgesic effects of ibuprofen gargle after mandibular third molar extractions. Participants were categorized as responders (n = 13) and non-responders (n = 22) based on the within-subject difference (ibuprofen-placebo, IP) of visual analog scale (VAS) changes. Baseline characteristics were compared, along with variables, such as age, sex, the reason for extraction, extraction site, Pell Gregory (space and depth) classification, Winter's classification, surgeon's experience, and surgery time. Baseline characteristics predicting responder status were examined using multivariate logistic regression. Results In the univariate analysis, variables such as age, sex, and baseline VAS scores with p-values <0.2 were evaluated using a stepwise approach. This analysis identified age (per -10 years) with an odds ratio of 4.163 (95% confidence interval (CI): 1.170-31.952, p = 0.0233) and sex (female) with an odds ratio of 9.977 (95% CI: 1.336-208.256, p = 0.0213) as significant predictors of responder status. Conclusions In young and female patients, ibuprofen gargle decreased postoperative pain after mandibular third molar extractions.

Transcutaneous carbon dioxide suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.

Cancer cachexia causes skeletal muscle atrophy, impacting the treatment and prognosis of patients with advanced cancer, but no treatment has yet been established to control cancer cachexia. We demonstrated that transcutaneous application of carbon dioxide (CO2) could improve local blood flow and reduce skeletal muscle atrophy in a fracture model. However, the effects of transcutaneous application of CO2 in cancer-bearing conditions are not yet known. In this study, we calculated fat-free body mass (FFM), defined as the skeletal muscle mass, and evaluated the expression of muscle atrophy markers and uncoupling protein markers as well as the cross-sectional area (CSA) to investigate whether transcutaneous application of CO2 to skeletal muscle could suppress skeletal muscle atrophy in cancer-bearing mice. Human oral squamous cell carcinoma was transplanted subcutaneously into the upper dorsal region of nude mice, and 1 week later, CO2 gas was applied to the legs twice a week for 4 weeks and FFM was calculated by bioimpedance spectroscopy. After the experiment concluded, the quadriceps were extracted, and muscle atrophy markers (muscle atrophy F-box protein (MAFbx), muscle RING-finger protein 1 (MuRF-1)) and uncoupling protein markers (uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3)) were evaluated by real-time polymerase chain reaction and immunohistochemical staining, and CSA by hematoxylin and eosin staining. The CO2-treated group exhibited significant mRNA and protein expression inhibition of the four markers. Furthermore, immunohistochemical staining showed decreased MAFbx, MuRF-1, UCP2, and UCP3 in the CO2-treated group. In fact, the CSA in hematoxylin and eosin staining and the FFM revealed significant suppression of skeletal muscle atrophy in the CO2-treated group. We suggest that transcutaneous application of CO2 to skeletal muscle suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.

Construction of a versatile in vitro cultivation screening platform using human oral microbiota.

We developed a simulation model of human oral microbiota using Bio Palette oral medium (BPOM) containing 0.02% glucose and lower bacterial nitrogen sources, derived from saliva and dental plaque. By decreasing the concentration of Gifu anaerobic medium (GAM) from 30 to 10 g L-1 , we observed increased ratios of target pathogenic genera, Porphyromonas and Fusobacterium from 0.5% and 1.7% to 1.2% and 3.5%, respectively, in the biofilm on hydroxyapatite (HA) discs. BPOM exhibited the higher ratios of Porphyromonas and Fusobacterium, and amplicon sequence variant number on HA, compared with GAM, modified GAM and basal medium mucin. Mixing glycerol stocks of BPOM culture solutions from four human subjects resulted in comparable ratios of these bacteria to the original saliva. In this simulation model, sitafloxacin showed higher inhibitory effects on P. gingivalis than minocycline hydrochloride at a low dosage of 0.1 µg mL-1 . Probiotics such as Streptococcus salivarius and Limosilactobacillus fermentum also showed significant decreases in Porphyromonas and Fusobacterium ratios on HA, respectively. Overall, the study suggests that BPOM with low carbon and nutrients could be a versatile platform for assessing the efficacy of antibiotics and live biotherapeutics in treating oral diseases caused by Porphyromonas and Fusobacterium.

Differential Photosensitivity of Fibroblasts Obtained from Normal Skin and Hypertrophic Scar Tissues.

It is unclear whether normal human skin tissue or abnormal scarring are photoreceptive. Therefore, this study investigated photosensitivity in normal skin tissue and hypertrophic scars. The expression of opsins, which are photoreceptor proteins, in normal dermal fibroblasts (NDFs) and hypertrophic scar fibroblasts (HSFs) was examined. After exposure to blue light (BL), changes in the expression levels of αSMA and clock-related genes, specifically PER2 and BMAL1, were examined in both fibroblast types. Opsins were expressed in both fibroblast types, with OPN3 exhibiting the highest expression levels. After peripheral circadian rhythm disruption, BL induced rhythm formation in NDFs. In contrast, although HSFs showed changes in clock-related gene expression levels, no distinct rhythm formation was observed. The expression level of αSMA was significantly higher in HSFs and decreased to the same level as that in NDFs upon BL exposure. When OPN3 knocked-down HSFs were exposed to BL, the reduction in αSMA expression was inhibited. This study showed that BL exposure directly triggers peripheral circadian synchronization in NDFs but not in HSFs. OPN3-mediated BL exposure inhibited HSFs. Although the current results did not elucidate the relationship between peripheral circadian rhythms and hypertrophic scars, they show that BL can be applied for the prevention and treatment of hypertrophic scars and keloids.

Risk factors associated with prognosis of patients with medication-related osteonecrosis of the jaw.

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect of antiresorptive and/or antiangiogenic agents. As the treatment application for MRONJ is controversial, we aimed to identify the risk factors for poor prognosis and to help determine appropriate management. METHODS: This study included 119 patients. Relevant clinical data were obtained for all the patients. In computed tomography images, osteosclerosis, osteolysis, cortical perforation (buccal or lingual), periosteal reaction, and sequestration were evaluated. RESULTS: Multivariate analyses showed statistically significant associations between poor prognosis in patients with MRONJ and conservative treatment alone (hazard ratio [HR] 1.89), osteolysis (HR 4.67), and the absence of sequestration (HR 5.33). CONCLUSIONS: Conservative treatment alone without clear objectives needs to be avoided, and osteolytic change could be the criteria for surgical intervention. As the boundary between the lesion and vital bone is indistinct, we recommend extensive surgery in cases with unpredictable sequestration.

Efficacy of perioperative oral care management in the prevention of surgical complications in 503 patients after pancreaticoduodenectomy for resectable malignant tumor: A multicenter retrospective analysis using propensity score matching.

BACKGROUND: Pancreaticoduodenectomy has been associated with a high mortality rate and significant postoperative morbidity. Recently, perioperative oral care management has been reported to be effective in preventing postoperative pneumonia and surgical site infection. In this study, we examined the effect of perioperative oral care management in reducing complications after pancreaticoduodenectomy, including surgical site infection. METHODS: This retrospective multicenter study included 503 patients who underwent pancreaticoduodenectomy at 8 facilities between January 2014 and December 2016. Among these, 144 received perioperative oral management by dentists and dental hygienists (oral management group), whereas the remaining 359 did not (control group). The oral care management program included oral health instructions, removal of dental calculus, professional mechanical tooth cleaning, removal of tongue coating, denture cleaning, instructions for gargling, and tooth extraction. The participants were matched using propensity scores to reduce background bias. Various factors were examined for correlation with the development of complications. RESULTS: The incidence of organ/space surgical site infection was significantly lower in the oral management group than in the control group (8.0% vs 19.6%, P = .005). Multivariable logistic regression analysis revealed that hypertension and lack of perioperative oral management were independent risk factors for organ/space surgical site infection. Lack of perioperative oral management had an odds ratio of 2.847 (95% confidence interval 1.335-6.071, P = .007). CONCLUSION: Perioperative oral care management reduces the occurrence of surgical site infections after pancreaticoduodenectomy and should be recommended as a strategy to prevent infections in addition to antibiotic use.

Tooth Loss as a Predictor of Long-Term Care Requirements in the Elderly: A Study in Kobe City, Japan.

INTRODUCTION: The Kobe project, which utilizes prospective data from the national health insurance system, focuses on early detection and preventive strategies through the Frail Kenshin health check-up program. Previous research has underscored the correlation between tooth loss and the decline in physical and cognitive functions. In this study, using Kobe project data, we examined the link between remaining teeth and long-term care needs in individuals aged 64-65 years, with primary and secondary objectives involving various health parameters and quality of life. METHODS: We analyzed baseline data from a prospective study conducted alongside the Frail Check program for generally healthy individuals aged 64-65 years to examine the relationship between the number of remaining teeth and various health indicators. This study focused on citizens aged 64-65 years to identify those at risk of needing long-term care by the age of 65 years. RESULTS: Data from 1,530 participants were obtained, excluding eight individuals for specific reasons. At the end of the follow-up period, 41 (2.7%) individuals required support and 15 (1.0%) needed long-term care alone. The data revealed a significant association between the number of remaining teeth and the need for long-term care or support, as demonstrated by the Cochran-Armitage trend test (p<0.001). Although trends were noted for nutrition and total Cognitive Functional Instrument Self scores, they did not reach statistical significance. Additionally, a decrease in the number of remaining teeth was significantly associated with worse European Quality of Life Five Dimensions (EQ-5D-5L) visual analog scale scores, mobility, and regular activities (p<0.001). CONCLUSION: Tooth loss indicates the potential long-term care needs of older adults. Monitoring oral health is crucial for addressing care requirements.

Gold Nanoparticles Enhance the Tumor Growth-Suppressing Effects of Cetuximab and Radiotherapy in Head and Neck Cancer In Vitro and In Vivo.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) treatment includes surgery, radiotherapy, and immunotherapy with the aim of eradicating cancer cells without affecting normal tissues. HNSCC expresses epidermal growth factor receptor (EGFR) and cetuximab, an IgG1 monoclonal antibody targeting epidermal growth factor receptor, has been approved for the treatment of HNSCC. However, cetuximab has low reactivity and induces serious side effects. Gold nanoparticles (AuNPs) were reported to enhance the local antitumor effects of radiotherapy without damaging normal cells. METHODS AND RESULTS: This study investigated the in vitro effects of single and combination therapy with AuNPs (1.0 nM), cetuximab (30 nM), and radiotherapy (4 Gy) on a human HNSCC cell line, HSC-3. Combination treatment of AuNPs + cetuximab + radiotherapy markedly reduced HSC-3 numbers and proliferation and enhanced apoptosis compared with single and double combination treatments. Furthermore, the in vivo combination treatment (AuNPs + cetuximab + radiotherapy) of a xenograft model of HSC-3 cells transplanted into nude mice (BALB/cAJcl-nu/nu) reduced the tumor volume compared with the controls. Scanning electron microscopy demonstrated the presence of AuNPs in tumor tissues and toxicity analysis indicated that AuNPs had no toxic effect on normal tissues. CONCLUSIONS: This study showed that AuNPs alone do not have a tumor-suppressing effect, but they sensitize tumors to radiotherapy and bind to cetuximab, leading to enhanced antitumor effects.

The Efficacy of Carbon Dioxide Paste in Alleviating Pain in Patients After Neck Dissection: Protocol for a Double-Blinded, Randomized Controlled Trial.

BACKGROUND: Head and neck cancers that cause severe aesthetic and functional disorders normally metastasize to the cervical lymph nodes. Patients with cervical lymph node metastasis are undergoing neck dissection. Shoulder complaints are common after neck dissection, with patients reporting symptoms such as pain, weakness, shoulder droop, and disability. However, no safe and effective treatment is available for this condition at present. We will conduct a double-blinded, randomized controlled trial to evaluate the efficacy of carbon dioxide (CO2) paste in relieving pain in patients after neck dissection. OBJECTIVE: This will be the first clinical study to compare the efficacy of CO2 paste with placebo in relieving postoperative pain in patients who underwent neck dissection. METHODS: We will perform this trial at the Kobe University Hospital in Japan. Patients will be randomized 1:1 into the CO2 paste and control groups. Patients in the CO2 paste group will have the CO2 paste applied to the cervical surface skin for 10 minutes once per day for 14 consecutive days. The primary end point of the study is a change in the visual analog scale (VAS) scores of neck pain from baseline on day 1 (preapplication) to the end of drug application (day 15). Secondary end points include changes in the following parameters from baseline on day 1 to the end of drug application (day 15) or the study (day 29): neck pain VAS score (days 1-29), grip strength (days 1-15 and 1-29), VAS scores for subjective symptoms (the feeling of strangulation, numbness, swelling, and warmth in the neck and shoulder region) for days 1-15 and 1-29, whether the VAS score improved more than 30% (days 1-15), the arm abduction test (days 1-15 and 1-29), shoulder range of motion (abduction and flexion) for days 1-15 and 1-29, occurrence of skin disorders, and occurrence of serious side effects. Periodic monitoring will be conducted for participants during the trial. This study was approved by the certified review board of Kobe University. RESULTS: The intervention commenced in May 2021 and will continue until March 2024. The collected data will provide information on the efficacy of the CO2 paste treatment. The primary end point will be compared using the Wilcoxon test, with the 1-sided significance level set at 5%. Each evaluation item will be summarized. Secondary efficacy end points will be analyzed to provide additional insights into the primary analysis. Findings based on the treatment effects are expected to be submitted for publication in 2025. CONCLUSIONS: This trial will provide exploratory evidence of the efficacy and safety of CO2 paste in relieving pain in patients after neck dissection. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier: jRCTs051210028; https://jrct.niph.go.jp/en-latest-detail/jRCTs051210028. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50500.

Efficacy and safety of ibuprofen gargle for postoperative pain after mandibular third molar extraction: A phase II, placebo-controlled, double-blind, randomized crossover trial.

OBJECTIVE: This study was designed to evaluate the postoperative efficacy and safety of using an ibuprofen gargle as a pain management strategy for patients who have undergone mandibular third molar extraction. We also ensured that the quality of treatment was not compromised throughout the study. MATERIAL AND METHODS: Patients were randomized in a 1:1 ratio into two groups: the ibuprofen-placebo (IP) group and the placebo-ibuprofen (PI) group. On postoperative Day (POD) 1, the IP group initiated ibuprofen administration, while the PI group started taking placebo. On POD 2, the IP group switched to using placebo, whereas the PI group switched to ibuprofen. From PODs 3-5, both groups were prescribed ibuprofen gargle. The primary endpoint was within-subject visual analog scale (VAS) score before and 5 min after the first use of the ibuprofen or placebo gargle on PODs 1 and 2 (ΔVAS5_ibuprofen - ΔVAS5_placebo ). The incidence and severity of adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0 and a subjective rating scale. RESULTS: This study enrolled 40 patients. The within-subject VAS5 of the IP and PI groups were 1.25 ± 12.0 and -5.26 ± 8.93 mm, respectively. The treatment effect of ibuprofen gargle was -2.01 ± 10.62 mm (p = .246). None of the patients in each group presented with serious adverse events or clinically significant complications (including dry sockets) after extraction. Transient adverse events, such as throat tingling and oral discomfort (grade 1), were observed in each group. CONCLUSION: Ibuprofen gargle was safe but did not provide significant pain relief when used after mandibular third molar extraction.

Development of Cu application using dual-energy computed tomography for detecting medication-related osteonecrosis of the jaw.

INTRODUCTION: The present study developed an application using dual-energy computed tomography (DECT) focused on Cu for detecting medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: First, we performed two types of phantom studies using a Cu wire syringe and pig mandible with Cu wire to detect Cu on DECT. Second, DECT examinations of 44 patients with MRONJ were performed to compare lesion and normal bone sites using single-energy CT, DECT-virtual non-calcium (VNCa), and DECT-Cu applications. Quantitative analyses of VNCa CT and CT values were performed, and a cut-off value was calculated using receiver operating characteristic analysis. Third, we compared the Cu content in the MRONJ and normal bone groups using inductively coupled plasma atomic emission spectroscopy (ICP-AES). RESULTS: The material-specific differences in attenuation between the two different energies enabled the accurate separation of Cu from Ca in phantom studies. The sensitivity and specificity for single-energy CT, DECT-VNCa, and DECT-Cu applications were 97.7% and 2.3%, 86.4% and 81.8%, and 88.6% and 97.7%, respectively. Thus, VNCa CT values obtained on DECT-Cu application images showed the highest area under the curve value and maximal diagnostic efficacy in differentiating lesion sites from normal bone sites. On ICP-AES analyses, the Cu content was significantly higher in the MRONJ group than in the normal bone group. CONCLUSION: DECT-Cu application demonstrated better diagnostic performance in detecting MRONJ compared with single-energy CT or DECT-VNCa.

Photodynamic therapy with verteporfin accelerates apoptotic bleb formation in human ameloblastoma.

OBJECTIVE: Although benign, ameloblastoma is a locally aggressive lesion in some patients and the development of additional treatments is needed. Verteporfin (VP) is a photosensitizer exhibiting considerable photocytotoxicity in various tumor cells. We aimed to investigate the effects of verteporfin photodynamic therapy (VP PDT) on ameloblastoma. METHODS: Eighteen patients who underwent surgery for ameloblastoma were randomly selected. We performed an immunohistochemical assessment to investigate the expression of low-density lipoprotein receptor (LDLR) and Yes-associated protein (YAP), targets of VP, in human ameloblastoma tissues and cultured human ameloblastoma cell line (HAM1). The effect of VP PDT on cell proliferation and apoptosis in HAM1 was analyzed. RESULTS: The expression of LDLR and YAP were detected in human ameloblastoma tissues and HAM1. LDLR expression was significantly higher in patients who had previously undergone surgery than in patients who were receiving it for the first time. The cytotoxic effect of the combination of low-concentration VP administration and laser irradiation was comparable to high-concentration VP administration with and without laser irradiation. The addition of laser irradiation to VP administration significantly accelerated apoptotic bleb formation compared with VP administration alone. CONCLUSION: VP PDT has the potential to become an additional treatment for large-sized ameloblastoma.

Relationship of Mitochondrial-Related Protein Expression with the Differentiation, Metastasis, and Poor Prognosis of Oral Squamous Cell Carcinoma.

Mitochondrial dysfunction and respiratory function changes have been consistently associated with the initiation and progression of cancer. The purpose of this study was to retrospectively investigate the expression of mitochondrial tumor-suppressor and DNA-repair proteins in patients with oral squamous cell carcinoma (OSCC) and to evaluate the relationship between their expression and prognosis. We enrolled 197 patients with OSCC who underwent surgical resection between August 2013 and October 2018. Clinical, pathological, and epidemiological data were retrospectively collected from hospital records. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A, mitochondrial tumor suppressor gene 1, silent information regulator 3, and 8-hydroxyguanine DNA glycosylase was investigated using immunochemistry. The 3-year disease-specific survival (DSS) rates of patients showing positive expression of all selected proteins were significantly higher than those of patients showing a lack of expression. Multivariate analysis revealed that the expression of PGC-1α (hazard ratio, 4.684) and vascular invasion (hazard ratio, 5.690) can predict the DSS rate (p < 0.001). Low PGC-1α expression and vascular invasion are potential clinically effective predictors of the prognosis of OSCC.

Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Cancer-associated fibroblasts (CAFs) are the main stromal cells in the tumor microenvironment (TME). As CAFs promote tumor progression and hypoxia in the TME, regulating the conversion of normal fibroblasts (NFs) into CAFs is essential for improving the prognosis of patients with OSCC. We have previously reported the antitumor effects of transcutaneous carbon dioxide (CO2) application in OSCC. However, the effects of reducing hypoxia in the TME remain unclear. In this study, we investigated whether CO2 administration improves the TME by evaluating CAFs marker expression. Human OSCC cells (HSC-3) and normal human dermal fibroblasts (NHDF) were coinjected subcutaneously into the dorsal region of mice. CO2 gas was applied twice a week for 3 weeks. The tumors were harvested six times after transcutaneous CO2 application. The expression of CAFs markers (α-SMA, FAP, PDPN, and TGF-ß) were evaluated by using real-time polymerase chain reaction and immunohistochemical staining. The expression of α-SMA, FAP, PDPN, and TGF-ß was significantly increased over time after co-injection. In the CO2-treated group, tumor growth was significantly suppressed after treatment initiation. In addition, the mRNA expression of these markers was significantly inhibited. Furthermore, immunohistochemical staining revealed a significant decrease in the protein expression of all CAFs markers in the CO2-treated group. We confirmed that transcutaneous CO2 application suppressed CAFs marker expression and tumor growth in OSCC xenograft mouse model.

Comparison of the 8th edition of TNM staging of oral cancer with the 7th edition and its prognostic significance using clinical depth of invasion and extranodal extension.

OBJECTIVES: The 8th edition of the International Union Against Cancer Control/American Joint Committee on Cancer Staging System introduced depth of invasion (DOI) and extranodal extension (ENE) into the staging of oral cavity cancer. We evaluated the prognostic ability of this new staging system compared with the 7th edition using clinical DOI (cDOI) and clinical ENE (cENE). MATERIALS AND METHODS: We retrospectively reviewed and restaged 2,118 patients with oral squamous cell carcinoma treated between 2001 and 2018 using cDOI and cENE. Overall and disease-specific survival were used as endpoints to compare the prognostic outcomes of the 7th and 8th editions using Harrell's concordance index (C-index). RESULTS: In total, 305 (14.4 %) cases were upstaged in the T category, 85 (4.0 %) cases were upstaged in the N category, and 280 (13.2 %) cases were upstaged in the overall TNM stage. The introduction of the cDOI increased the C-index and hazard ratio (HR) for each T category. The introduction of cENE increased the N3b category of 85 cases, bringing the total to 94 cases, thereby widening the differences between each N category. In the 8th edition, the C-index and HR for overall TNM stage increased, and the discrimination between stage groups improved. CONCLUSIONS: The 8th edition of the TNM clinical staging system using cDOI and cENE predominantly identified patients with a high mortality rate, thus improving the ability to discriminate and prognosticate oral cancer.

A Novel Imaging Technique for Analyzing Condylar Movement During Mastication in Patients With Jaw Deformities: Four-Dimensional Computed Tomography.

OBJECTIVE: This study aimed to reveal characteristic condylar movements in patients with jaw deformities. STUDY DESIGN: Thirty patients with jaw deformities before surgery were enrolled and instructed to chew a cookie during 4-dimensional computed tomography (4DCT). The distance between the most anterior and posterior positions of the bilateral condyles on 4DCT images was measured and compared among patients with different skeletal classes. Correlations between the condylar protrusion and cephalometric values were also determined. RESULTS: The distances of condylar protrusion during mastication were significantly greater in the skeletal class II group than in the skeletal class III group ( P =0.0002). Significant correlations were found between the distances of condylar protrusion during mastication and the sella-nasion-B point angle ( r =-0.442, P =0.015), A point-nasion-B point angle ( r =0.516, P =0.004), sella-nasion plane to ramus plane angle ( r =0.464, P =0.01), sella-nasion plane to occlusal plane angle ( r =0.367, P =0.047), and condylion-gonion length ( r =-0.366, P =0.048). CONCLUSION: Motion analysis with 4DCT images revealed that condylar movement in patients with retrognathism was larger than in patients with mandibular prognathism. Skeletal structure was therefore correlated with condylar movement during mastication.

Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan.

Background/purpose: The incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ. Materials and methods: After excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose. Results: Low doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy. Conclusion: To the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses.

Expression of JCAD and EGFR in Perineurial Cell-Cell Junctions of Human Inferior Alveolar Nerve.

Although perineurium has an important role in maintenance of the blood-nerve barrier, understanding of perineurial cell-cell junctions is insufficient. The aim of this study was to analyze the expression of junctional cadherin 5 associated (JCAD) and epidermal growth factor receptor (EGFR) in the perineurium of the human inferior alveolar nerve (IAN) and investigate their roles in perineurial cell-cell junctions using cultured human perineurial cells (HPNCs). In human IAN, JCAD was strongly expressed in endoneurial microvessels. JCAD and EGFR were expressed at various intensities in the perineurium. In HPNCs, JCAD was clearly expressed at cell-cell junctions. EGFR inhibitor AG1478 treatment changed cell morphology and the ratio of JCAD-positive cell-cell contacts of HPNCs. Therefore, JCAD and EGFR may have a role in the regulation of perineurial cell-cell junctions.