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Critical flicker fusion frequency (CFF) is a short but sensitive method for evaluating optic nerve function. We measured CFF in patients with pituitary neuroendocrine tumors (Pit-NETs) to assess its usefulness. Data from 184 patients with nonfunctioning Pit-NETs, who had been treated with transsphenoidal surgery and had no medical history of eye diseases, was used in this retrospective study. Visual acuity decline (VAD) was defined as > 0.10 reduction in logMAR visual acuity and CFF decline (CFD) was defined as CFF value < 35 Hz. Visual field defect (VFD) was evaluated by automated perimetry on a Humphrey visual field analyzer. Potential associations between abnormal test results and tumor height from the suprasellar were analyzed. Contact between the optic nerve or chiasma and the tumor was present and absent in 161 and 23 patients, respectively. In patients showing contact, the difference in CFF between the left and right eyes was larger (p = 0.0008), and the optimal cutoff value using the receiver operating characteristic curve was 3 Hz. Therefore, ≥ 3 Hz was considered positive for CFF laterality (CFL), the most prevalent condition. Tumor height was lower in patients with CFL positivity compared to those with VAD or VFD (p < 0.01). The prevalence of test abnormalities was the highest for small tumors compared to those of other tests. Changes in CFL permit early detection of Pit-NETs. Our results indicate that CFF laterality can be seen in the early stages of compressive optic neuropathy due to Pit-NET. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the invasiveness to surrounding structures and recurrence rate of each subtype of nonfunctioning pituitary neuroendocrine tumor (Pit-NETs) according to the WHO 2022 classification. Methods: This retrospective study utilized data from 292 patients with nonfunctioning Pit-NETs treated with initial transsphenoidal surgery. Recurrence was evaluated on 113 patients who were available for a magnetic resonance imaging follow-up ≥ 60 months. All tumors were assessed by immunohistochemical staining for Pit-1, T-PIT, and GATA3. Invasiveness to surrounding structures was evaluated based on intraoperative findings. Results: Cavernous sinus invasion was found in 47.5% of null cell tumors, 50.0% of Pit-1 lineage tumors, 31.8% of corticotroph tumors, and 18.3% of gonadotroph tumors. Dura mater defects in the floor of sellar turcica, indicating dural invasion, were found in 44.3% of null cell tumors, 36.4% of corticotroph tumors, 16.7% of Pit-1 lineage tumors, and 17.3% of gonadotroph tumors. In logistic regression analysis, Pit-1 (OR 5.90, 95% CI 1.71–20.4, P = 0.0050) and null tumors (OR 4.14, 95% CI 1.86–9.23, P = 0.0005) were associated with cavernous sinus invasion. Recurrence was found in 8 (4.9%) patients, but without significant differences between tumor subtypes. The presence of cavernous sinus invasion was correlated with recurrence (HR = 1.95, 95% CI 1.10–3.46, P = 0.0227). Conclusion: Among nonfunctioning Pit-NETs, Pit-1 lineage tumors tend to invade the cavernous sinus, corticotroph tumors may produce dura mater defects, and null cell tumors tend to cause both. Pit-NETs with cavernous sinus invasion require a careful attention to recurrence. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected stage 0 ONJ between patients treated with sequential therapy comprising weekly teriparatide for 72 weeks followed by alendronate for 48 weeks vs. those who received monotherapy with alendronate for 120 weeks. Materials and methods: Suspected stage 0/1 ONJ was defined by non-specific symptoms. Tooth mobility and periodontal symptoms (gingival bleeding, swelling, and/or pain) were selected as clinical findings of suspected stage 0 ONJ. Poisson regression models were applied to calculate the incidence rate ratios of suspected stage 0/1 between the teriparatide group (TG) and alendronate group (AG). Generalized linear models were used to calculate the risk ratios of clinical findings between groups. Results: Two hundred and sixty-one participants in the TG and 344 in the AG answered a structured questionnaire on oral health and were included in this study. There were no significant differences between the groups in the incidence rate of suspected stage 0/1 ONJ at both 72 and 120 weeks. The risk ratio of the TG to AG for tooth mobility was 0.34 (95% confidence interval [CI] 0.13–0.88, p = 0.02) at 72 weeks and 0.90 (95% CI 0.40–2.03, p = 0.83) at 120 weeks. The incidence rate of tooth mobility related to periodontal symptoms decreased in the TG and increased in the AG during the study. Conclusion: Tooth mobility accompanied by clinical periodontal symptoms may be a useful early sign of stage 0 ONJ. [ABSTRACT FROM AUTHOR]

Introduction: A 2015 survey of the Japan Osteoporosis Society (JOS) on medication-related osteonecrosis of the jaw (MRONJ) revealed that cooperation between physicians and dentists was poor. Discontinuation of antiresorptive agents before tooth extraction was found to increase adverse events without preventing MRONJ. We compared this 2015 survey with a new survey conducted in 2022 to investigate cooperation between physicians and dentists for MRONJ. Materials and methods: A web-based structured questionnaire including 13 key queries was sent to 3813 physicians who were members of JOS, and 1227 (32.2%) responses were received. Results: Of the 1227 respondents, 909 (74.1%) had complied with a discontinuation request from a dentist before tooth extraction, although 25.4% of medications were not related to the incidence of MRONJ. Of these, 177 respondents reported 252 adverse events including 10 (1.3%) cases of MRONJ. The prevalence of fractures increased from 4.8% in 2015 to 8.2% in 2022. The rates of respondents who requested oral health care by a dentist before antiresorptive agent therapy and reported cooperation between physicians and dentists were 72.7% and 42.4% in 2022 compared with 32.9% and 24.8% in 2015, respectively. The rates of cooperation among the 47 prefectures in Japan were significantly different, ranging from 10.0 to 83.3% (p = 0.02). Conclusion: This study confirmed increased cooperation between physicians and dentists for MRONJ in Japan. However, a more equal distribution of cooperation across Japan is necessary to optimally manage MRONJ. Discontinuation of antiresorptive agents is no longer necessary because fractures during discontinuation continue to increase in Japan. [ABSTRACT FROM AUTHOR]

Background: The treatment response of primary central nervous system lymphomas (PCNSLs) is mainly evaluated using postcontrast T1-weighted imaging (T1WI). Because poorly enhanced lesions may contain residual tumors, the combination of evaluation methods will potentially improve the accuracy of determining treatment effectiveness. In this study, we evaluated the usefulness of diffusion-weighted imaging (DWI) in predicting recurrence among patients with PCNSL who achieved complete response (CR)/unconfirmed CR (CRu). Methods: Fifty-four patients newly diagnosed with PCNSL who were treated at our institution and achieved CR/CRu at the end of treatment were included in this study. The patients were divided into two groups according to the presence or absence of residual DWI hyperintense signal at the tumor site at the end of treatment. Kaplan–Meier analysis was performed to analyze the median overall survival (OS) and progression-free survival (PFS). Results: The mean age of the 54 patients was 66.4 ± 13.3 years. The induction therapies were HD-MTX in 20 patients, R-MPV in 29 patients, and other chemotherapies in five patients. Radiotherapy was performed in 35 patients, high-dose cytarabine therapy in 14 patients, and autologous hematopoietic stem cell transplantation in one patient, and of the 54 patients, 10 had no consolidation therapy. The residual DWI hyperintense signal sign was observed in 18 patients. The R-MPV regimen was statistically associated with a lower rate of residual DWI hyperintense signal (p = 0.0453). The median PFS was statistically shorter in the residual DWI hyperintense signal group than in the non-residual DWI hyperintense signal group (14.0 months vs. 85.1 months) (p < 0.0001, log-rank test). Conclusion: A residual DWI hyperintense signal at the end of treatment was statistically associated with shorter PFS. Among patients who achieved CR/CRu evaluated based on postcontrast T1WI, DWI could be a valuable additional sequence to predict the early recurrence of PCNSL. [ABSTRACT FROM AUTHOR]

Purpose: Due to the effectiveness of growth hormone therapy (GHT), the number of cancer survivors receiving GHT has increased. Previous studies had indicated that GHT was not associated with the increasing risks of tumor recurrence and development with second neoplasm (SN) in cancer survivors. However, to date, research on those risks in germinoma survivors is still limited. The aim of this study is to evaluate the impact of GHT in relation to tumor recurrence and development with SN in pure germinoma survivors. Methods: This retrospective cohort study was approved by the Ethical Committee for Epidemiology of our institution. Seventy-three consecutive patients who underwent a biopsy of the lesion and were diagnosed with pure germinoma were retrospectively studied. They (median age, 15.0 years) were followed up more than 1 year after biopsy (median follow-up period, 14.3 years). The following data was obtained from the medical records of the patients: age, sex, preoperative magnetic resonance imaging findings, hormonal replacement, and events including tumor recurrence and/or SN. Results: In our patient series, 16 patients (21.9%) who were more likely to have neurohypophysial lesion and receive multiple hormonal therapies had received GHT. No significant differences in the rates of tumor recurrence and development with SN were observed between the patients who had and had not received GHT. Moreover, the recurrence-free survival and overall survival rates were not different between the patients who had and had not received GHT. Conclusions: GHT did not increase the risks of tumor recurrence and development with SN in pure germinoma survivors. [ABSTRACT FROM AUTHOR]

Introduction: The so-called radiation-induced glioma (RIG, a secondary glioma after cranial irradiation), is a serious late effect after cranial radiation therapy. The clinical characteristics of and ideal treatment for these tumors are unclear. We analyzed our case series and conducted a comprehensive literature review to reveal the precise characteristics of RIGs. Methods: We analyzed the cases of six patients with RIGs treated at our institution and 354 patients with RIGs from the literature. The latency period from irradiation to the development of each RIG and the median overall survival of the patients were subjected to Kaplan–Meier analyses. Spearman's correlation test was used to determine the relationship between age at irradiation and the latency period. Results: The mean age of the 360 patients at the development of RIG was 27.42 ± 17.87 years. The mean latency period was 11.35 ± 8.58 years. Multiple gliomas were observed in 28.4%. WHO grade 3 and 4 RIGs accounted for 93.3%. The latency periods were significant shorter in the higher WHO grade group (p = 0.0366) and the concomitant systemic chemotherapy group (p < 0.0001). Age at irradiation was negatively associated with the latency period (r =− 0.2287, p = 0.0219). The patients treated with radiotherapy achieved significantly longer survival compared to those treated without radiotherapy (p = 0.0011). Conclusions: Development in younger age, multiplicity, and high incidence of grade 3 and 4 are the clinical characteristics of RIGs. Cranial irradiation at older ages and concomitant chemotherapy were associated with shorter latency for the development of RIG. Radiation therapy may be the feasible treatment option despite radiation-induced gliomas. [ABSTRACT FROM AUTHOR]

Introduction: Little is known about whether substances inducing tissue protein degeneration in the oral cavity are associated with the number of teeth present in postmenopausal women. We sought to investigate the association of urinary pentosidine and serum homocysteine levels with the number of teeth and subsequent tooth loss in Japanese postmenopausal women. Materials and methods: Among participants in the Nagano Cohort Study, 785 postmenopausal women (mean age, 68.1 years) participated in the present study. The number of teeth was re-counted at the time of follow-up in 610 women. Poisson regression analysis was used to investigate differences in the number of teeth among quartiles of pentosidine or homocysteine, adjusting for covariates that correlated with the number of teeth. A Cox proportional hazard model was used to evaluate the association of subsequent tooth loss with pentosidine or homocysteine levels. Results: Pentosidine quartiles were not associated with the number of teeth at baseline. Participants in the highest homocysteine quartile had significantly fewer teeth at baseline than those in the third and lowest quartiles (p < 0.001 for both). Those in the second quartile had fewer teeth than those in the third (p = 0.001) and lowest (p < 0.001) quartiles. An increased risk of tooth loss during follow-up was significantly associated with higher urinary pentosidine (hazard ratio = 1.073 for 10 pmol/mgCre; p = 0.001). Conclusion: Postmenopausal women with higher homocysteine levels had fewer teeth at baseline. A higher pentosidine concentration increased the risk of subsequent tooth loss. High pentosidine or homocysteine concentrations may be associated with tooth loss in postmenopausal women. [ABSTRACT FROM AUTHOR]

Increased physical activity is required in patients with stroke that are hospitalized in the rehabilitation unit. This study investigated the association between the daily number of steps and walking independence in order to determine the cutoff value of daily number of steps that can predict walking independence in hospitalized patients with sub-acute stroke. This cross-sectional observational study included 85 stroke patients admitted to the rehabilitation unit. The average daily number of steps was measured using Fitbit One for 4 days starting at 30 days after stroke onset. 6-min walk test, and Fugl-Meyer assessment of the lower extremities were measured The category of walking independence was classified using the Functional Ambulation Category (FAC). The subjects were divided into two groups according to the FAC score: a walking independence group (FAC ≥ 4) and a walking non-independence group (FAC ≤ 3). Logistic regression analysis was conducted to investigate the association of daily number of steps with walking independence and a receiver operating characteristic curve was used to identify the cutoff value of daily number of steps for predicting walking independence. The daily number of steps (per 1000 steps) was independently associated with walking independence (odds ratio (OR); 2.53, 95% confidence interval (CI); 1.40–5.73, p = 0.009). The cutoff value of daily number of steps for predicting independent walking was 4286 steps (area under the curve = 0.914, sensitivity of 0.731, and specificity of 0.949). The daily number of steps was associated with independent walking in hospitalized patients with sub-acute stroke. The daily number of steps may be a useful target in rehabilitation for patients with sub-acute stroke. [ABSTRACT FROM AUTHOR]

Osteoporosis is becoming a global health issue due to increased life expectancy. However, it is difficult to detect in its early stages owing to a lack of discernible symptoms. Hence, screening for osteoporosis with widely used dental panoramic radiographs would be very cost-effective and useful. In this study, we investigate the use of deep learning to classify osteoporosis from dental panoramic radiographs. In addition, the effect of adding clinical covariate data to the radiographic images on the identification performance was assessed. For objective labeling, a dataset containing 778 images was collected from patients who underwent both skeletal-bone-mineral density measurement and dental panoramic radiography at a single general hospital between 2014 and 2020. Osteoporosis was assessed from the dental panoramic radiographs using convolutional neural network (CNN) models, including EfficientNet-b0, -b3, and -b7 and ResNet-18, -50, and -152. An ensemble model was also constructed with clinical covariates added to each CNN. The ensemble model exhibited improved performance on all metrics for all CNNs, especially accuracy and AUC. The results show that deep learning using CNN can accurately classify osteoporosis from dental panoramic radiographs. Furthermore, it was shown that the accuracy can be improved using an ensemble model with patient covariates. [ABSTRACT FROM AUTHOR]

Purpose: Diabetes insipidus (DI) following transsphenoidal surgery (TSS) is a common complication. Although postoperative DI often occurs in patients with craniopharyngioma and Rathke's cleft cyst, postoperative DI in patients with non-functioning pituitary adenoma (NFPA) has not been fully examined. We clarified the clinical characteristics and magnetic resonance imaging (MRI) findings predicting postoperative DI in NFPAs. Methods: A total of 333 patients undergoing initial TSS for NFPA were included in this retrospective study. Hyperintensity (HI) in the posterior pituitary lobe was evaluated on preoperative T1-weighted MRI. Based on the findings of HI patients were divided into three groups as follows: HI was not detected (Disappearance group), HI located intrasellarly (Intrasellar group), and HI located suprasellarly (Suprasellar group). Results: The overall rate of DI was 21.9%, including permanent DI in 0.6%. DI occurred at postoperative day 1 (72.6%) or day 2 (19.2%) and improved within 7 days in most cases (87.7%). Univariable and multivariable analyses showed that the predictive factors of DI were a younger age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95–0.99, P = 0.0037) and larger tumor diameter (OR 1.04, 95% CI 1.01–1.08, P = 0.0155). The rate of DI was highest in the Disappearance group (43.8%) followed by the Intrasellar group (26.0%). The OR was 2.17 in the Intrasellar group compared with the Suprasellar group (95% CI 1.17–4.02, P = 0.0141). Conclusions: Factors predicting DI following TSS for NFPA were a younger age, larger tumor size, and the location of intrasellar HI on preoperative T1-weighted MRI. [ABSTRACT FROM AUTHOR]

Summary: Japanese postmenopausal women with symptomatic periodontal disease had a significantly smaller increase in the T-score for total hip bone density than those without periodontal disease during medication therapy for osteoporosis. Intervention to treat symptomatic periodontal disease before and/or during osteoporosis therapy could maintain the effect of osteoporosis medications. Purpose: Women with periodontal disease may be more likely to develop osteoporosis. We evaluated whether the presence of symptomatic periodontal disease can influence changes in skeletal bone mineral density (BMD) during medication therapy for osteoporosis in Japanese postmenopausal women. Methods: A total of 4,258 postmenopausal women participated in the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-04 trial) and number 5 (JOINT-05 trial), which were multi-center, open-label, randomized controlled trials in Japan. Of these, 3,670 non-edentulous subjects participated in the study. Subjects who had self-reported symptoms of periodontal disease at baseline were defined as having periodontal disease. The study outcome was the difference in BMD changes during the study between subjects with and without periodontal disease. Mixed models for repeated measures after adjusting for covariates were used to investigate the difference in the BMD changes during the study between subjects with and without periodontal disease. Results: Subjects with periodontal disease had significantly lower T-scores for total hip (p = 0.035) and metacarpal (p = 0.048) BMD than those without periodontal disease at baseline. During medication therapy for osteoporosis, subjects with periodontal disease had a significantly smaller increase in T-score for total hip BMD than those without periodontal disease (p = 0.021), although no significant differences were observed in the changes in T-scores for other skeletal BMD measurements between subjects with and without periodontal disease. Conclusions: The presence of self-reported symptoms of periodontal disease may be associated with a decrease in the effect of osteoporosis medications in Japanese postmenopausal women. [ABSTRACT FROM AUTHOR]

Purpose: Thyrotropin-secreting pituitary adenomas (TSPA) are extremely rare pituitary adenomas; their perioperative thyroid hormone dynamics have not been completely elucidated. Here, we investigated the clinical characteristics, perioperative findings, and thyroid hormone dynamics of TSPA at a single institution. Methods: We enrolled 11 patients who underwent transsphenoidal surgery (TSS) for TSPA during 2005–2019 at Hiroshima University Hospital (TSPA group) and 24 patients who underwent TSS for nonfunctioning pituitary adenomas (NFPA) in 2019 (NFPA group; for comparison). Their clinical characteristics, operative findings, and thyroid hormone dynamics, including serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were retrospectively analyzed. Results: The NFPA group demonstrated a slight temporary decrease in serum TSH/ FT3/ FT4 levels on day 1 postoperatively and improvement in the levels on day 4 postoperatively. In contrast, the serum TSH level in the TSPA group demonstrated a marked decrease on day 1 postoperatively but improved on day 7 postoperatively. The serum FT3 level was also markedly decreased on day 1 postoperatively but remained within the normal range. The serum FT4 level revealed a gradual decrease until day 21 postoperatively and then recovered within the normal range 3 months postoperatively. There was no significant difference in the frequency of decline in serum FT4 level between the two groups; no patients required thyroid hormonal replacement 3 months postoperatively. Conclusions: Despite a variable degree of transient hypothyroidism, all patients had a normal thyroid function after 3 months follow-up. [ABSTRACT FROM AUTHOR]

Osteoporotic fractures are associated with an increased risk of subsequent fractures, a higher rate of mortality, and incremental medical costs. Incidental findings, which include some measurements related to the mandibular inferior cortex and the alveolar trabecular bone pattern of the mandible determined on panoramic radiographs, are considered to be a useful tool for identifying asymptomatic individuals at risk of having osteoporosis and/or fragility fractures. We undertook a worldwide literature survey and present the following clinical recommendations. Postmenopausal female dental patients with a mandibular inferior cortical width of less than 3 mm on panoramic radiographs may be at risk of having low skeletal bone mineral density (BMD) or osteoporosis, but not fragility fractures. In addition, those with a severely eroded mandibular inferior cortex may have an increased risk of having low skeletal BMD, osteoporosis, and fragility fractures. The alveolar trabecular bone pattern of the mandible might be useful for identifying female dental patients at risk of having fragility fractures, although further investigation is necessary to confirm this possibility. These incidental findings on panoramic radiographs, when used for identifying asymptomatic postmenopausal female patients at risk of having osteoporosis in general dental practice, may be helpful in reducing the incidence of first fractures, with a consequent reduction in the secondary fractures, medical costs, and mortality associated with osteoporotic fragility fractures, without incurring any additional cost. [ABSTRACT FROM AUTHOR]

Background: A pial arteriovenous fistula (pAVF) is a rare condition characterized by a direct connection between a cerebral artery and cerebral vein without an intervening nidus. The prognosis is poor in untreated cases with hemorrhagic manifestations, indicating that surgical treatment is desirable. We describe a successful endovascular treatment for a pediatric case of ruptured pAVF located at the bottom of the sulcus. Clinical description: An 11-year-old girl presented with severe headache and mild disturbance of consciousness. Head computed tomography showed hemorrhage in the callosal sulcus and ventricle. Cerebral angiography showed an arteriovenous shunt without a nidus. The branching artery from the pericallosal artery was connected directly to the thalamostriate vein without varix, and the shunt point was located at the bottom of the callosal sulcus. The patient was diagnosed with pAVF involving a single feeder and single drainer. Emergency endovascular transarterial embolization was performed using 20% N-butyl cyanoacrylate, and the shunt disappeared completely without complications. The patient was discharged with no neurological deficits. Conclusion: Endovascular treatment is feasible, safe, and effective for pediatric cases of deeply located pAVF. [ABSTRACT FROM AUTHOR]

Introduction: Fragility fractures can cause delayed wound healing after tooth extraction, which contributes to an increased risk of osteomyelitis of the jaw. We evaluated whether a history of fragility fracture was associated with increased risk of delayed wound healing after tooth extraction in older adults in Japan.Materials and Methods: Of 5352 people aged 50-89 years in the 2014 basic resident registry of the town of Obuse, the present study included 376 subjects (190 men and 186 women) who completed a structured questionnaire and measurement of the bone mineral densities (BMDs) of the bilateral femoral neck. Delayed wound healing after tooth extraction was self-reported. Fragility fractures were confirmed via examination of hospital medical records. Logistic regression analyses adjusted for age and gender were used to evaluate association of clinical variables with delayed would healing after tooth extractions. Odds ratios (ORs) and the 95% confidence intervals (CIs) of all possible associated variables for the presence of delayed wound healing were calculated.Results: Subjects with a history of fragility fractures had a significantly higher risk of delayed wound healing compared with those without previous fragility fractures (OR 2.68; 95% CI 1.11-6.46, p = 0.028). This association still remained after adjusted for all other variables (OR 2.70; 95% CI 1.10-6.60, p = 0.030). Delayed wound healing was not significantly associated with the BMD of the femoral neck.Conclusions: History of fragility fracture may be associated with increased risk of delayed wound healing after tooth extraction in Japanese men and women aged 50-89 years. [ABSTRACT FROM AUTHOR]

Children with optic pathway gliomas (OPGs) frequently suffer from problems of visual function resulting from tumors. Previous reports showed that bevacizumab improved visual function in patients with OPG via tumor response to treatment. In these two case reports, we show that bevacizumab improved visual field without tumor response as seen in imaging. Both, a 10-year-old girl and a 6-year-old boy, had previous history of treatment with platinum-based chemotherapy. They had visual deterioration without tumor progression on MR imaging. Bevacizumab effectively and immediately improved visual field in both patients without imaging response of OPG. We emphasize that bevacizumab should be considered for patients with OPGs having visual deterioration without tumor progression. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the jaw (ONJ) associated with bisphosphonate therapy is a rare but severe side effect in osteoporosis patients. Recently, the number of osteoporosis patients with ONJ has dramatically increased in Japan. This has contributed to an increase in the number of patients avoiding extractions. However, there has been no prospective study providing definitive incidence data for ONJ in Japanese patients. The purpose of this study was to elucidate the true as well as suspected incidence of ONJ. A total of 3229 subjects (1612 subjects in the minodronic acid group and 1617 subjects in the raloxifene group) in the Japanese Osteoporosis Intervention Trial protocol number 4 participated in this study. ONJ was diagnosed by experienced dentists. Suspected Stage 0 and 1 (bone exposure of the jaw) ONJ was assessed by a structured questionnaire at baseline and at 6, 12, 18, and 24 months. No established ONJ cases were diagnosed during the study. The incidence of suspected Stage 0 and/or Stage 1 ONJ was 6.14 per 1000 patient-years in the minodronic acid group and 3.38 per 1000 patient-years in the raloxifene group [hazard ratio (95% confidence interval) = 1.82 (0.84-3.93), P = 0.13]. Approximately 50-60% of bone exposures that appeared during the study had disappeared at the next observation. Although the subjects in this study may have developed a greater interest in the health of the oral cavity, the incidence of ONJ after minodronic acid treatment would be lower than the expected incident rate. [ABSTRACT FROM AUTHOR]

We planned to conduct multi-center, open-labeled, blinded-endpoints, head-to-head randomized trial of minodronate and raloxifene to compare incidences of vertebral and non-vertebral fractures. The study is the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-4). Here, we present the pre-fixed study design. The inclusion criteria are ambulatory older women with osteoporosis, aged > 60 years, and without pre-specified risk factors for secondary osteoporosis and dementia. The subjects who meet selection criteria will be randomly allocated to the raloxifene (60 mg/day) or minodronate (1 mg/day or 50 mg/4 weeks) groups using the central registry. The co-primary endpoints are osteoporotic (vertebral, humeral, femoral, and radial), vertebral, and major osteoporotic (clinical vertebral, humeral, femoral, and radial) fractures. Furthermore, we plan to use the Hochberg procedure to preserve an overall type 1 error rate. In addition, changes in bone mineral density (BMD), hip-structure analysis (HSA) variables, height, bone turnover markers, serum cholesterol and triglyceride concentrations, dental health questionnaire, fall frequency, fall risk index, nursing care level, physical function, quality of life (QOL), and safety profiles were assessed as secondary endpoints. To detect 24% reduction of major osteoporotic fractures with 80% power and a two-sided significance level of 5% with a 2-year observation period, 1734 patients/treatment arm would be required. Subgroup analysis stratified to the following factors age, body mass index, BMD, 25-hydroxyvitamin D concentration, estimated glomerular filtration rate (eGFR), prevalent vertebral fracture number, hypertension status, and diabetes mellitus is pre-specified. The protocol is registered in the trial registry system, and the trial identification number is UMIN000005433. [ABSTRACT FROM AUTHOR]

Objectives: Patients undergoing osteoporosis treatment benefit greatly from early detection. We previously developed a computer-aided diagnosis (CAD) system to identify osteoporosis using panoramic radiographs. However, the region of interest (ROI) was relatively small, and the method to select suitable ROIs was labor-intensive. This study aimed to expand the ROI and perform semi-automatized extraction of ROIs. The diagnostic performance and operating time were also assessed. Methods: We used panoramic radiographs and skeletal bone mineral density data of 200 postmenopausal women. Using the reference point that we defined by averaging 100 panoramic images as the lower mandibular border under the mental foramen, a 400 × 100-pixel ROI was automatically extracted and divided into four 100 × 100-pixel blocks. Valid blocks were analyzed using program 1, which examined each block separately, and program 2, which divided the blocks into smaller segments and performed scans/analyses across blocks. Diagnostic performance was evaluated using another set of 100 panoramic images. Results: Most ROIs (97.0%) were correctly extracted. The operation time decreased to 51.4% for program 1 and to 69.3% for program 2. The sensitivity, specificity, and accuracy for identifying osteoporosis were 84.0, 68.0, and 72.0% for program 1 and 92.0, 62.7, and 70.0% for program 2, respectively. Compared with the previous conventional system, program 2 recorded a slightly higher sensitivity, although it occasionally also elicited false positives. Conclusions: Patients at risk for osteoporosis can be identified more rapidly using this new CAD system, which may contribute to earlier detection and intervention and improved medical care. [ABSTRACT FROM AUTHOR]

Objectives: To assess intra- and inter-observer agreement in the morphological evaluation of mandibular cortical bone on panoramic radiographs, to examine factors affecting the diagnosis, and to determine causes of diagnostic discrepancy. Methods: Three experienced observers evaluated mandibular cortical shape on panoramic radiographs of 228 females, and divided the images into three classes. The intra- and inter-observer agreements were calculated. The effect of mandibular cortical width on shape classification was examined. Causes of diagnostic discrepancy were investigated. Results: Overall intra- and inter-observer kappa values in diagnosing mandibular cortical shape were 0.58-0.76 and 0.62-0.69, respectively. The kappa values in diagnosing Class 2 were low. In radiographs diagnosed as Class 2 and Class 3, the ranges of mandibular cortical width overlapped. Discrepancies in diagnosis were caused by slight resorption at the endosteal margin of the cortical bone, endosteal cortical residues near the thinned smooth cortex, and superimposition of the hyoid bone over the mandible. Conclusions: Inter-observer agreement in evaluating mandibular cortical shape was moderate to substantial. Diagnostic discrepancies were mainly caused by differences in evaluation of the endosteum near the cortical bone. [ABSTRACT FROM AUTHOR]

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an intractable, though rare, complication in cancer patients with bone metastases and patients with osteoporosis who are treated with antiresorptive agents, including bisphosphonates and denosumab. Despite the more than 10 years that have passed since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were reported, our understanding of the epidemiology and pathophysiology of ARONJ remains limited, and data supported by evidence-based medicine are still sparse. However, the diagnosis and staging of ARONJ, identification of risk factors, and development of preventive and therapeutic approaches have advanced significantly over the past decade. The Position Paper 2017 is an updated version of the Position Paper 2010 of the Japanese Allied Committee on Osteonecrosis of the Jaw, which now comprises six Japanese academic societies. The Position Paper 2017 describes a new diagnostic definition for ARONJ, as proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), summarizes our current understanding of the pathophysiology of ARONJ based on a literature search, and suggests methods for physicians and dentists/oral surgeons to manage the disease. In addition, the appropriateness of discontinuing antiresorptive medications (drug holiday) before, during, and after invasive dental treatments is discussed extensively. More importantly, the manuscript also proposes, for the first time, the importance of interactive communication and cooperation between physicians and dentists/oral surgeons for the successful treatment of ARONJ. The Position Paper 2017 is intended to serve as a guide for improving the management of ARONJ patients in Japan. [ABSTRACT FROM AUTHOR]

The error has now been corrected and this patient data has been removed in the Supplementary Information file. After publication it transpired that the Supplementary Information file which accompanies the Article, inadvertently contained confidential patient data. [Extracted from the article]

Dentists request a discontinuation of antiresorptive agents, such as bisphosphonate, before and after tooth extractions to prevent osteonecrosis of the jaw (ONJ). However, little is known about how this affects ONJ and osteoporosis treatment and how medical professionals and dentists cooperate to treat ONJ in patients with osteoporosis. This study aimed to clarify the impact of ONJ on osteoporosis treatment in Japan. A structured questionnaire including 14 key clinical queries was sent to 488 medical professionals as part of the Japanese Osteoporosis Intervention Trial (JOINT)-04, and 206 responses were received. A total of 173 respondents had received discontinuation requests from dentists. Of these, 28 respondents experienced 30 adverse events including ten fractures and one incidence of ONJ. The respondents who refused discontinuation requests observed no cases of ONJ. Approximately 16 % of respondents had patients who discontinued osteoporosis treatment, following a requested drug discontinuation, after tooth extraction. Dentists requested discontinuations for many medications that were not associated with the incidence of ONJ. Approximately 76 % of respondents had never requested oral health care from dentists before osteoporosis treatment and 72 % reported no cooperation between dentists and medical professionals in their region. Our results suggest that drug discontinuation may increase adverse events and disturb osteoporosis treatment without completely preventing ONJ. Currently, both medical professionals and dentists in Japan still continue to recommend their own treatment position. A forum to share information about ONJ among medical professionals, dentists, and patients is required. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to assess the association between the cortical shape of the mandible, as detected on panoramic radiographs, and trabecular bone structure, as assessed by cone-beam computed tomography (CBCT), in Japanese adults. Methods: Panoramic radiographs and CBCT images of the mandibles of 50 subjects (18 men, 32 women), aged 45-86 years, were evaluated. An experienced oral and maxillofacial radiologist categorized the cortical shape of the mandible as detected on panoramic radiographs as normal, mildly to moderately eroded, and severely eroded cortices, respectively. All mandibles were scanned using CBCT. Four bone structure parameters of the basal portion of the mandible were calculated in three dimensions using an image-analysis system: total bone volume (mm); cortical bone volume fraction (%); trabecular bone volume fraction (%); fractal dimension. One-way analysis of covariance with Bonferroni correction was employed to evaluate differences in the four bone parameters among the three cortical shape groups. Pearson's correlation coefficient was calculated to examine correlations between age and cortical and trabecular bone volume fractions. Results: Progression of cortical bone erosion was significantly associated with increased trabecular bone volume fraction ( P < 0.001) and increased fractal dimension ( P = 0.01). Cortical bone volume fraction decreased significantly with age ( P = 0.04). However, trabecular bone volume fraction tended to increase with age ( P = 0.06). Conclusions: The change in the trabecular bone structure of the mandible may differ from that of the general skeleton in Japanese adults. [ABSTRACT FROM AUTHOR]

Objectives: Digital subtraction radiography (DSR) is a suitable technique for detecting incipient bone changes. However, in DSR, one or more follow-up radiographs must be taken. The aim of this study was to assess the possibility of reducing the exposure time for the radiographs that follow the initial one. Methods: Maxillary premolar and molar radiographic images of a dry skull were taken with a digital radiography system. The initial radiographs, without bone chips, were taken at 0.32 and 0.16 s. Then, five bone chips (weight range 7-15 mg) were placed on the maxillary molar buccal side of the dry skull. Secondary radiographs were taken at 0.32-, 0.16-, 0.08-, 0.04-, and 0.02-s exposure times. For each bone chip, radiographs were taken three times. The secondary and initial images were subtracted to yield subtraction images. Four observers were asked to evaluate bone change visibility in the subtraction images. The Friedman test was used for statistical analysis. Results: Significant differences were seen at each of the settings for the 0.32-s group ( p = 1.24e−030) and 0.16-s group ( p = 7.52e−009). By comparing the different groups, observer evaluations indicated that visibility changed when the secondary radiograph was taken at 1/8 of the exposure time of the initial radiograph. In both groups, the visibility of the 0.02-s subtraction image was significantly lower than that of the other subtraction images. Conclusion: In DSR, the exposure time of the secondary radiograph can be reduced to 1/4 of the exposure time of the initial radiograph. [ABSTRACT FROM AUTHOR]

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is becoming common in Japan. Oral and maxillofacial radiologists must diagnose BRONJ in general practice. However, little information on how to recognise BRONJ is available. The purpose of this study, therefore, was to confirm the recognition of BRONJ among Japanese oral and maxillofacial radiologists. Methods: A questionnaire including 14 main queries and relevant branch queries was created and sent to 29 Japanese institutions employing oral and maxillofacial radiologists. Results: A large number of patients (705) with BRONJ during the last 3 years were reported by 23 institutions (25 responders) that participated in our survey. The rate of osteonecrosis of the jaw associated with intravenous bisphosphonates was almost identical to that associated with oral bisphosphonates. This finding was inconsistent with worldwide data. About half of the responders felt that the diagnosis of BRONJ based on imaging was difficult. No specific modality was selected for identifying the early signs of BRONJ, although 19 responders selected multi-detector computed tomography followed by magnetic resonance imaging as the best modality for determining the extent of BRONJ. Almost all responders felt that the detection of early signs and determination of lesion extent on imaging were important roles of oral and maxillofacial radiologists. Conclusions: Oral and maxillofacial radiologists recognised their roles in BRONJ diagnosis; however, insufficient evidence regarding the accomplishment of these roles is available. Japanese oral and maxillofacial radiologists must accumulate a large number of BRONJ images, analyse them in cooperation with one another and share the information obtained from their analysis. [ABSTRACT FROM AUTHOR]

Objectives: Rubber dams increase the quality and safety of dental treatment. However, the condition of a rubber dam over an open mouth may also obstruct the route for respiration. We tested whether an open mouth with or without a rubber dam would affect upper airway patency and breathing pattern. Materials and methods: Twenty young healthy volunteers were imaged with a magnetic resonance (MR) system under three conditions: mouth closed, mouth open, and rubber dam with mouth open. Respiration was concurrently monitored with plethysmography. MRI slices of the upper airway were obtained at 5-mm thicknesses, and the size of the cross-sectional area of the upper airway was measured by image analysis software. Respiratory cycle duration and tidal volume were also measured with digital signal analysis software. Results: The volume of the upper airway became significantly decreased with the mouth open. Analysis of each cross-sectional area of the upper airway revealed that while the oropharyngeal area was significantly narrower with an open mouth, the retropalatal and hypopharyngeal areas were not affected. Placing a rubber dam had no additional influence on upper airway patency but was seen to significantly shorten mean respiratory duration and decrease tidal volume. Conclusions: Open mouth position plays the largest role in decreased upper airway patency, and open mouth position with a rubber dam may further disrupt breathing pattern. Clinical relevance: Breathing pattern may become deteriorated by airway obstruction during dental treatments requiring a rubber dam. [ABSTRACT FROM AUTHOR]

Bisphosphonates (BPs) have been widely, efficiently, and safely used for the treatment of osteoporosis, malignant hypercalcemia, bone metastasis of solid cancers, and multiple myeloma bone diseases. Accumulating recent reports describe that surgical dental treatments in patients with cancer or osteoporosis who have been receiving intravenous or oral BPs are associated with osteonecrosis of the jaw (bisphosphonate-related osteonecrosis of the jaw, BRONJ). The accurate incidence, clinical backgrounds, and pathogenesis of BRONJ have been unclear and appropriate approaches for prevention and treatment have not been established to date. To address the current situation of BRONJ in Japan, the "Allied Task Force Committee of Bisphosphonate-Related Osteonecrosis of the Jaw," consisting of physicians specializing in bone biology, orthopedic surgery, rheumatology, obstetrics/gynecology, and medical oncology and dentists specializing in oral surgery, periodontology, dental radiology, and oral pathology, was organized. The committee attempted to propose a standard position paper for the treatment of BRONJ. The committee expects that this proposal will provide objective and correct scientific information on BRONJ and will serve as a reference for conducting dental procedures for patients receiving BPs and in designing prevention and treatment of BRONJ. However, because this position paper is not based on direct clinical evidence, it should be used as a reference, and a decision on treatment in each case should be made after an extensive discussion among physicians, dentists/oral surgeons, and the patients. [ABSTRACT FROM AUTHOR]

Introduction: Eroded or thin inferior cortex of the mandible detected on dental panoramic radiographs may be useful for identifying postmenopausal women with low bone mineral density (BMD) or osteoporosis. The purpose of this study was to evaluate whether these panoramic measurements are useful for identifying low BMD or osteoporosis in postmenopausal women younger than 65 years. Methods: We compared the diagnostic performances of panoramic measurements with those of the osteoporosis self-assessment tool (OST) for identifying women with low BMD (T-score of −2.0 or less at either the lumbar spine or the femoral neck) and osteoporosis (T score of −2.5 or less) in 158 healthy Japanese postmenopausal women aged 46 years to 64 years. Mandibular cortical shape (erosion) and width were evaluated on dental panoramic radiographs. Receiver operating characteristic curve analysis was used to determine the optimal cutoff thresholds for cortical width and OST index. Results: The sensitivity and specificity, respectively, for identifying women with low BMD were 82.3% and 55.2% for OST index, 79.0% and 50.0% for cortical width, and 72.6% and 74.0% for cortical shape. The sensitivity and specificity, respectively, for identifying women with osteoporosis were 86.7% and 46.9% for OST index, 90.0% and 45.3% for cortical width, and 86.7% and 65.6% for cortical shape. Likelihood ratio for identifying women with low BMD was 13.90 for thin cortical width (<3.0 mm) and 10.84 for severely eroded cortex. That for identifying women with osteoporosis was 6.40 for thin cortical width and 7.11 for severely eroded cortex. Conclusions: Dentists may be able to refer postmenopausal women younger than 65 years for bone densitometry on the basis of incidental findings on dental panoramic radiographs. [ABSTRACT FROM AUTHOR]

Dentists are a potentially valuable resource for initial patient screening for signs of osteoporosis, as individuals with osteoporosis have altered architecture of the inferior border of the mandible as seen on panoramic radiographs. Our aim was to evaluate the efficacy of combining clinical and dental panoramic radiographic risk factors for identifying individuals with low femoral bone mass. Bone mineral density was measured at the femoral neck and classified as normal, osteopenic or osteoporotic using WHO criteria in 227 Japanese postmenopausal women (33-84 years). Panoramic radiographs were made of all subjects. Mandibular cortical shape and width was determined and trabecular features were measured in each ramus. Mean subject age, height, and weight were significantly different in the three bone-density groups (P<0.0001). A classification and regression trees (CART) analysis using just clinical risk factors identified 136 (87%) of the 157 individuals with femoral osteopenia or osteoporosis. Mean mandible cortical width (P<0.0001), cortical index (P<0.0001) and trabecular features (P=0.02) were also significantly different in the three bone density groups. A CART analysis considering only radiographic features found 130 (83%) of the 157 individuals with femoral osteopenia or osteoporosis, although none of the subjects with osteoporosis was correctly identified. A CART analysis using both clinical and radiographic features found that the most useful risk factors were thickness of inferior border of the mandible and age. This algorithm identified 130 (83%) of the 157 individuals with femoral osteopenia or osteoporosis. The results of this study suggest that 1) clinical information is as useful as panoramic radiographic information for identifying subjects having low bone mass, and 2) dentists have sufficient clinical and radiographic information to play a useful role in screening for individuals with osteoporosis. [ABSTRACT FROM AUTHOR]

The purpose of this case-control study was to determine if elderly subjects with a history of osteoporotic fractures have fewer teeth and greater residual ridge resorption than subjects without such fractures. Patients older than 60 with a panoramic radiograph were invited to a phone interview. Information was obtained regarding fracture history, smoking, and hormone replacement therapy (HRT). The number of teeth was obtained from the panoramic radiograph. The residual ridge height of the edentulous mandible was measured at the site of the mental foramen. Multiple regression models were used to assess the association between fracture status and number of teeth or residual ridge height (controlling for age, gender, HRT, smoking, height and weight). Cases (n=93) were individuals reporting osteoporotic fractures (fractures occurring after minor impact). Controls (n=394) were individuals reporting traumatic fractures (n=105) or no fractures (n=289). Fracture status in this population affect neither the number of teeth nor the residual ridge height. In the regression model, the variables that had a statistically-significant effect on the number of teeth were age (p<0.0001) and smoking (p<0.0001). There was a dose-effect of smoking on the number of teeth. In the regression model, the variables that had a significantly-significant on residual ridge height (n=95 edentulous subjects) were age and gender. Our conclusion was that in elderly dental-school patients the number of teeth and residual ridge height were not influenced by fracture status. Age and smoking had the most influence ; there was no effect from HRT. The clinical implication is that a history of osteoporotic fractures is not an important cause for tooth loss and residual ridge resorption in an elderly dental-school population. [ABSTRACT FROM AUTHOR]

Recent studies suggest that a small number of remaining teeth may be associated with low skeletal bone mineral density (BMD) in postmenopausal women. Estrogen deficiency after menopause is considered potential cause relating to tooth loss accompanied by low skeletal BMD in women. Since estrogen plays a dominant role in regulating the male skeleton, it is likely that a small number of remaining teeth also may be associated with low skeletal BMD in men. However, it remains uncertain whether tooth loss is associated with low skeletal BMD in both men and women. We investigated the association between self-reported number of remaining teeth and BMD of the spine and the femoral neck in a cohort of 1914 Japanese subjects aged 48-95 years who were recruited from the Adult Health Study conducted by the Radiation Effects Research Foundation (RERF). BMD of the spine and the femoral neck was measured by dual energy X-ray absorptiometry (DXA). Tooth count was self-reported in response to a simple question to subjects about the number of remaining teeth they had at the time of the survey. Multiple regression analysis adjusted for age, weight, height, smoking, estrogen use, and years since menopause revealed a significant association between number of remaining teeth and BMD of the femoral neck in both men and women; however, no association was found between number of remaining teeth and BMD of the spine in both sexes. Retention of four teeth was significantly associated with a 0.004 g/cm2 increase in femoral neck BMD in men (P<0.05), which was similar to that observed in women (P<0.01). Our results suggest the presence of common causes, except age and body weight, relating to tooth loss accompanied by low BMD of the femoral neck in both men and women. [ABSTRACT FROM AUTHOR]

To assess the reproducibility of the mandibular cortical index (MCI) on panoramic radiographs among British and Japanese observers, and to investigate the difference between the British and Japanese observers in the definition of MCI. Three observers, a Japanese oral radiologist, a British oral radiologist, and a British prosthodontist, classified the inferior cortex of the mandible on a set of 100 duplicated films of randomly selected panoramic radiographs twice, 2 weeks apart, using the MCI. The kappa index for intra- and interobserver agreement was calculated for the three observers. The kappa index for intraobserver agreement was moderate (0.56) to perfect (0.86) for the three observers. Interobserver agreement between the Japanese and the British oral radiologists was moderate at the first reading (kappa, 0.59) and substantial at the second (0.61). Interobserver agreement between the prosthodontist on the one hand and each of the oral radiologists on the other was fair (0.35, 0.38) at the first reading, but moderate (0.43, 0.60) at the second reading. The prosthodontist tended to overestimate the MCI compared with either of the oral radiologists. Our results suggest that the definition of MCI used by Japanese observers is basically similar to that used by British observers, although some improvements in the definition of MCI would be necessary for clinical dental practice. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s12020-021-02614-3 [ABSTRACT FROM AUTHOR]

We reviewed the records for 4 patients with temporomandibular disorders (TMD), in all of whom temporomandibular joint (TMJ) arthrosis was initially suspected because of the clinical symptoms such as limited mouth opening and pain at the TMJ region. However, careful observation of the panoramic radiographs disclosed abnormalities other than TMJ arthrosis, including, obliteration of the posterior maxillary sinus wall (caused by squamous cell carcinoma of the maxillary sinus), resorption around the condylar neck (caused by hemangioma), and radiopaque foci at the anterior area of the right TMJ (synovial chondromatosis). Some of these abnormalities were not observed on the oblique lateral transcranial projection and the transorbital projection. Although panoramic imaging provides rather blurred images of the TMJ region it produces a broad image of the maxillofacial region which is helpful in the detection of neoplasms and other disorders. Its careful interpretation should be emphasized especially in the differential diagnosis of TMD. [ABSTRACT FROM AUTHOR]

An erratum to the article "Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw" that was published in the January 25, 2017 issue is presented.

It is unclear whether osteoporosis itself is a main risk factor for delayed wound healing after tooth extraction in humans. In this study, we evaluated the association between experience of delayed wound healing after last tooth extraction and self-reported kyphosis, with the possibility of having vertebral fractures, in Japanese patients. Among the 1,504 patients who responded to the structured questionnaire survey, 518 patients (134 men and 384 women) aged 55-97 years finally participated in this study. Patients who self-reported mild-moderate kyphosis were more likely to have problematic delayed wound healing after last tooth extraction than those who reported severe kyphosis (odds ratio [OR] 4.98; 95% confidence interval [CI], 1.86-13.38 and OR 2.30; 95% CI, 0.52-10.22, respectively) (p for trend = 0.005). Japanese patients with vertebral fractures may have a higher risk of having problematic delayed wound healing after tooth extraction. [ABSTRACT FROM AUTHOR]

A correction to the article "Association of cortical shape of the mandible on panoramic radiographs with mandibular trabecular bone structure in Japanese adults: A cone-beam CT-image analysis" that was published in the December 11, 2013 issue is presented.