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Objective The purpose of this study is to investigate the incidence and risk factor of ARONJ in patients receiving zoledronic acid, bisphosphonates (BP), or denosumab for bone metastases in urology or breast and endocrinology surgery. Patients The subjects were 567 patients who visited the department of urology or breast and endocrine surgery in Nagoya City University Hospital from August 2006 to March 2019 and who received zoledronic acid or denosumab for bone metastasis. Results Incidence of ARONJ The incidence of ARONJ in patients who received zoledronic acid alone, denosumab alone, and zoledronic acid plus denosumab was 1.9 %, 9.1 %, 7.6 %, respectively. Risk factors for ARONJ development The analysis of factors associated with the development of ARONJ with zoledronic acid alone revealed that hypocalcemia and the number of doses were significant risk factors. Risk of the onset of ARONJ due to drug change When the drug was changed from zoledronic acid to denosumab, the risk ratio for developing ARONJ was 3.6 times higher than that of the zoledronic acid alone group. Conclusions We consider that changing from zoledronic acid to denosumab is a risk factor for the development of ARONJ

Objective Platelet-rich fibrin (PRF) is a second-generation platelet concentrate. PRF has been the subject of both basic and clinical studies and has seen clinical application throughout the world with a focus on its tissue regeneration effect; however, few reports have focused on PRF's postoperative pain-relieving effect. Therefore, we prospectively examined the postoperative pain-relieving effect of PRF following tooth extraction. Patients Among the patients who visited the Oral and Maxillofacial Surgery Department at the our hospital from April 2016 to March 2018, there were 14 male and 18 female subjects who met the inclusion criteria. Results There were no significant differences in the average Visual Analog Scale (VAS) value between the PRF group and control group at the day of tooth extraction and day 2 after surgery, but at days 3 and 4 after surgery, the PRF group showed a significantly lower VAS value than the control group. Conclusions The present study proved the short-term efficacy of PRF immediately after surgery (within 1 week after surgery) for relieving pain.

Lower third molar extraction is the most common surgical treatment among routine dental and oral surgical procedures. while the surgical procedures for lower third molar extraction are well established, the difficulty of tooth extraction and the frequency of postoperative complications differ depending on the patient’s background. To establish a management protocol for the lower third molars, the prevalence of and risk factors for postoperative complications after lower third molar extraction were investigated in a large number of Japanese patients in a multicenter prospective study. During 6 consecutive months in 2020, 1826 lower third molar extractions were performed at the 20 participating institutions. The medical records of the patients were reviewed, and relevant data were extracted. The prevalence of and risk factors for postoperative complications were analyzed. The prevalence of postoperative complications after lower third molar extraction was 10.0%. Multivariate analysis indicated that age (≤32 vs >32, odds ratio [OR]: 1.428, 95% confidence interval [95% CI]: 1.040–1.962, P < .05), the radiographic anatomical relationship between the tooth roots and mandibular canal (overlapping of the roots and canal vs no close anatomical relationship between the roots and the superior border of the canal, OR: 2.078, 95% CI: 1.333–3.238, P < .01; overlapping of the roots and canal vs roots impinging on the superior border of the canal, OR: 1.599, 95% CI: 1.050–2.435, P < .05), and impaction depth according to the Pell and Gregory classification (position C vs position A, OR: 3.7622, 95% CI: 2.079–6.310, P < .001; position C vs position B, OR: 2.574, 95% CI: 1.574–4.210, P < .001) are significant independent risk factors for postoperative complications after lower third molar extraction. These results suggested that higher age and a deeply impacted tooth might be significant independent risk factors for postoperative complications after lower third molar extraction.

Little research has been conducted into hypoesthesia, and no studies have elucidated the risk factors for refractory hypoesthesia and compared treatment modalities. The purpose of this multicentre retrospective cohort study was to investigate the relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Risk factors for refractory hypoesthesia after oral surgery were evaluated using univariate and multivariate analysis. To minimize the selection bias associated with a retrospective data analysis, a propensity score analysis was performed between the medication and non-medication groups (65 sites in each group). Moderate or severe hypoesthesia (odds ratio 13.42) and no or late administration of ATP/vitamin B12 (odds ratio 2.28) were significantly associated with refractory hypoesthesia. In the propensity score analysis, the incidence rate of refractory hypoesthesia in the medication group was lower than that in the non-medication group (P

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event that may inhibit the treatment of primary disease and remarkably influence the patient's quality of life. The treatment methods for MRONJ, nonsurgical and surgical, are controversial, with no agreement as to which method provides the best outcome and should therefore be recommended. This multicenter retrospective study aimed to investigate the treatment methods and outcome in a large number of patients with MRONJ in Japan, utilizing propensity score matching analysis. A total of 361 patients with MRONJ, at eight hospitals, were registered in this study retrospectively. Various demographic and treatment-related variables were examined and analyzed to determine their correlation with the treatment outcome. After propensity score matching for treatment methods (nonsurgical versus surgical treatment), 176 patients were analyzed by logistic regression. It was shown that those with low-dose administration of an antiresorptive agent and surgical treatment had better outcomes. Furthermore, in 159 patients who underwent surgical treatment, those who underwent extensive surgery experienced significantly better treatment outcomes than those who underwent conservative surgery. This is the first study to compare treatment methods for MRONJ using propensity score matching analysis. The results indicated that extensive surgical treatment should be performed as first-choice therapy for patients with MRONJ. © 2017 American Society for Bone and Mineral Research.

Treatment strategies of medication-related osteonecrosis of the jaw (MRONJ) are controversial. Recently, surgical treatment has been reported as superior to nonsurgical treatment, but the contribution discontinued antiresorptive agent use during MRONJ treatment remains unclear. This study aimed to evaluate the efficacy of drug holidays and treatment strategies in MRONJ cases. Four-hundred and twenty-seven patients with MRONJ treated at nine hospitals from 2009 to 2017 were included in this multicenter retrospective study. Multivariate Cox regression analysis showed that the primary disease (osteoporosis or malignant tumor), diabetes, serum albumin, and treatment method (surgical or nonsurgical) were significantly correlated with the cure rate. The cumulative 1-year cure rates in the surgical and nonsurgical treatment groups were 64.7% and 18.2%, respectively. However, discontinuing antiresorptive agents did not influence the treatment outcome in the cohort overall, or in 230 patients after performing propensity score matching among the discontinuation and continuation groups. When stratifying by treatment method, antiresorptive agent discontinuation significantly increased the cure rate in patients with osteoporosis who underwent nonsurgical treatment. In patients with malignant tumors undergoing nonsurgical therapy, discontinuing the antiresorptive agent was associated with a better treatment outcome, but not with statistical significance. In contrast, drug holidays showed no effect on improving outcomes in patients with both osteoporosis and malignant tumors who underwent surgical therapy. Thus, regardless of the primary disease, discontinuing antiresorptive agents during treatment for MRONJ may not be necessary and may be helpful in some cases. Future prospective trials should examine this question further.

Pulsed electromagnetic fields (PEMFs) have been shown to be a noninvasive physical stimulant for bone fracture healing. However, PEMF stimulation requires a relatively long period of time and its mechanism of action has not yet been fully clarified. Recently, the mammalian target of rapamycin (mTOR) pathway has been shown to be involved in bone formation. This study aimed to investigate the effects of PEMFs on osteoblastic MC3T3-E1 cells by examining various cellular responses including changes in the mTOR pathway. Continuous PEMF stimulation induced a transient phosphorylation of the mTOR pathway, whereas intermittent PEMF stimulation (1 cycle of 10 min stimulation followed by 20 min of stimulation pause) revitalized the reduced phosphorylation. Moreover, PEMF stimulation stimulated cell proliferation (bromodeoxyuridine incorporation) rather than differentiation (alkaline phosphatase activity), with a more notable effect in the intermittently stimulated cells. These results suggest that intermittent PEMF stimulation may be effective in promoting bone fracture healing by accelerating cell proliferation, and in shortening stimulation time. Bioelectromagnetics. 2019;40:412-421. © 2019 Bioelectromagnetics Society.

Root amputation, immunosuppressive therapy, mandibular tooth extraction, pre-existing inflammation, and longer duration of treatment with bone-modifying agents were significantly associated with an increased risk of medication-related osteonecrosis of the jaw. Hopeless teeth should be extracted without drug holiday before the development of inflammation in cancer patients receiving high-dose bone-modifying agents. No studies have comprehensively analyzed the influence of pre-existing inflammation, surgical procedure–related factors such as primary wound closure, demographic factors, and drug holiday on the incidence of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this study was to retrospectively investigate the relationships between these various factors and the development of MRONJ after tooth extraction in cancer patients receiving high-dose bone-modifying agents (BMAs) such as bisphosphonates or denosumab. Risk factors for MRONJ after tooth extraction were evaluated with univariate and multivariate analyses. The following parameters were investigated in all patients: demographics, type and duration of BMA use, whether BMA use was discontinued before tooth extraction (drug holiday), the duration of such discontinuation, the presence of pre-existing inflammation, and whether additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed. We found that root amputation (OR = 22.62), immunosuppressive therapy (OR = 16.61), extraction of mandibular teeth (OR = 12.14), extraction of teeth with pre-existing inflammation, and longer duration (≥ 8 months) of high-dose BMA (OR = 7.85) were all significantly associated with MRONJ. Tooth extraction should not necessarily be postponed in cancer patients receiving high-dose BMA. The effectiveness of a short-term drug holiday was not confirmed, as drug holidays had no significant impact on MRONJ incidence. Tooth extraction may be acceptable during high-dose BMA therapy until 8 months after initiation.

Objective Oral mucositis is a common adverse reaction to radiotherapy for head and neck cancer, and there are concerns regarding a decreased quality of life in patients receiving radiotherapy. The purpose of this study was to investigate the relationship between the severity of radiation-induced oral mucositis and the myeloperoxidase (MPO) levels in irradiated tissues. Study Design Ninety-six F344 rats were divided into the following 4 groups: 10-Gy, 18-Gy, and 30-Gy irradiation groups, and a nonirradiation group. Oral mucositis was induced by the administration of single doses of radiation via exposure. After irradiation, the rats were evaluated on the basis of weight measurements, macroscopic findings according to a grading scale (Oral Mucositis Index [OMI]), and the results of tissue MPO assays. Results Weights decreased whereas the OMI scores and MPO levels increased, depending on the dose of exposure. The Spearman rank correlation test showed a significant correlation between the OMI scores and the MPO levels in the tissues with a correlation coefficient of 0.824 (P Conclusions In this study, the MPO levels in the irradiated tissue were increased in the cases involving severe radiation-induced oral mucositis evaluated in rats using a grading scale.

Objective The aim of this study was to evaluate the healing effect of topically applied platelet-rich fibrin (PRF) on experimental oral mucositis induced by chemotherapy in hamsters. Study Design Oral mucositis was induced in 93 Syrian golden hamsters by an intraperitoneal injection of 5-fluorouracil, which was followed by light scratching of the cheek pouch. The hamsters were randomly divided into a PRF group, a fibrin group, and an untreated control group. The recovery stage of oral mucositis was evaluated through daily weighing, measurements of the ulcer area, histopathologic analysis, and a myeloperoxidase activity assay. Results The PRF group exhibited significant improvements in the size and histologic features of the ulcer and in the myeloperoxidase activity compared with the control group ( P Conclusions The current findings suggest the consideration for future clinical trials in humans.

Noncentrosymmetic and chiral cocrystals were prepared from 2-amino-3-nitropyridine (2A3NP) and achiral benzenesulfonic acids (Ar-SO3H), which were designed for second-order nonlinear optical materials. Both components are commonly crystallized in 1:1 ionic forms of 2A3NPH+·Ar-SO3-. The molecular packings of cocrystals are controlled by the aromatic−aromatic interactions as well as multidirectional ionic and hydrogen bonds between the 2A3NPH+ cations and the sulfonate anions. The crystal of 2A3NP with p-toluenesulfonic acid belongs to acentric space group Pna21, in which 2A3NPH+ cations and anions are alternately stacked with some dihedral angle due to the large sulfonate anions to form two independent column structures in a perpendicular direction to each other. The crystal of 2A3NP with p-nitrobenzenesulfonic acid crystallizes into chiral space group P212121. The 2A3NPH+ cations and the anions are also alternately stacked to give herringbone network of 2A3NPH+ cations. The crystal of 2A3NP with 2,5-dimet...

Cocrystals were prepared from 2-amino-5-nitropyridine (2A5NP) and achiral benzenesulfonic acids (Ar–SO3H), which were designed for second-order nonlinear optical materials. Both components are commonly crystallized in 1:1 ionic forms of 2A5NPH+ · Ar–SO3 −. The cocrystal of 2A5NP with 2-nitrobenzenesulfonic acid belongs to acentric space group Pc, in which 2A5NPH+ cation and anion alternately stacked in almost parallel and superimposed manner to form column and layer structures. The cocrystal of 2A5NP with 3-nitrobenzenesulfonic acid is crystallized into chiral space group P212121. The 2A5NPH+ cation and anion are also alternately stacked with some dihedral angle to form column structures. These organic–organic cocrystals are controlled by the aromatic–aromatic interactions as well as multidirectional ionic and hydrogen bondings between the 2A5NPH+ cations and Ar–SO3 − anions. Second-harmonic generation (SHG) powers of the crystals measured by second-harmonic generation with evanescent wave (SHEW) techniqu...

In recent years, functional magnetic resonance imaging has been used to determine the interaction between chewing and brainactivity. However, the factors influencing the activity of the motor cortex have not been fully elucidated. Therefore, the presentstudy investigated the influence of the magnitude of bite force on brain activity. Fifteen right-handed healthy subjects (24-32 years; mean age, 27.8 years) were included. Sustained, constant clenching with small and large forces comprised the motortask. The spatial extent of the functional magnetic resonance imaging signal in the primary sensorimotor cortex increased withan increasing bite force in all subjects. These findings indicated the possibility of measuring the activated area in the primarysensorimotor cortex during clenching using functional magnetic resonance imaging, which revealed that the brain activity wasrelated to the magnitude of the bite force.

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