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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., (© 2023. The Japanese Society Bone and Mineral Research.)

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., (© 2023. The Japanese Society Bone and Mineral Research.)

Objectives: This study was performed to develop computer-aided screening systems that could predict osteoporosis. The systems were constructed using panoramic radiographs of women aged ≥ 50 years through three types of deep convolutional neural networks (CNNs): Alexnet, VGG-16, and GoogLeNet; the performances of the constructed systems were evaluated., Methods: One oral radiologist classified 1500 panoramic radiographs into three types. In C1, the endosteal margin of the cortex was smooth and sharp, whereas porosities were observed in C2 and C3. The risks of osteoporosis were higher in C2 and C3 than in C1; C3 had the highest risk. This information was included with the images as training data; three CNNs were transfer trained. Using each trained CNN, the diagnostic accuracy was assessed using panoramic radiographs and bone mineral density inspection findings in the lumbar spine and femoral neck of 100 additional patients., Results: All CNNs exhibited relatively good agreement with the oral radiologist's judgement (86.0%-90.7%). The predictive results of the three systems for osteoporosis of the lumbar spine showed sensitivities of 78.3%-82.6%, specificities of 71.4%-79.2%, and accuracies of 74.0%-79.0%. The predictive results for osteoporosis of the femoral neck showed sensitivities of 80.0%-86.7%, specificities of 67.1%-74.1%, and accuracies of 70.0%-75.0%., Conclusions: The constructed systems were generally more accurate than the previously developed conventional system. The new systems may facilitate osteoporosis prediction and prevent subsequent fractures by encouraging patients with suspected osteoporosis to undergo further inspections ( e.g ., dual-energy X-ray absorptiometry) and treatment.

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., (© 2022. The Author(s).)

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., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

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.

Osteoporosis (OP) is a common disease in the elderly that causes bone fractures and increases mortality. Denosumab (DMAB) is one of several medications to treat OP. DMAB not only reduces the risk of fractures, but also improves the quality of life. However, an increase in the risk of multiple vertebral fractures has been reported after DMAB discontinuation. We described the rare case of a 71-year-old woman with severe OP who experienced same-side insufficiency fractures of the tibia and femur at 18 months after DMAB discontinuation. Careful monitoring for both vertebral and lower limb fragility fractures is advised after DMAB cessation.

Purpose: To assess the mandibular cortical width (MCW) and morphology of the mandibular inferior cortex (MIC) on panoramic views from a large sample of males and females in various age groups by using an automated morphometric grading system for assisting osteoporosis screening. Furthermore, possible predictors and concrete cut-off values to identify the risk for osteoporosis were evaluated., Materials and Methods: MCW, MIC, tooth loss (TL), and alveolar bone loss (ABL) were retrospectively evaluated in 700 panoramic images from dental patients in Hong Kong using commercially available software. To estimate possible predictors for identifying the risk of osteoporosis, age, TL, and ABL were evaluated with the receiver operating characteristic (ROC) curves for each gender separately., Results: The age groups 60s (sixties), 70s and 80s showed statistically significant gender differences. For example, a smaller MCW and more MIC Class 3 were found in females. Furthermore, females exhibited a statistically significant increase in TL in the age groups 50 years and above. In males, age, TL or ABL did not correlate with MCW, whereas in females it statistically significantly did. Meanwhile, the correlation between ABL and MCW and MIC was weak for both genders. Concrete cut-off values to identify patients at risk of osteoporosis were 60.15 years and 3.5 missing teeth in females, and 72.55 years in males., Conclusion: Age and tooth loss were related to MCW and MIC in the population investigated. An age of ≥60 as well as more than 3.5 teeth lost seem to be indicators for a risk of osteoporosis in Chinese females based on panoramic views using artificial-intelligence-based software.

Objectives: A new computer-aided screening system for osteoporosis using panoramic radiographs was developed. The conventional system could detect porotic changes within the lower border of the mandible, but its severity could not be evaluated. Our aim was to enable the system to measure severity by implementing a linear bone resorption severity index (BRSI) based on the cortical bone shape., Methods: The participants were 68 females (>50 years) who underwent panoramic radiography and lumbar spine bone density measurements. The new system was designed to extract the lower border of the mandible as region of interests and convert them into morphological skeleton line images. The total perimeter length of the skeleton lines was defined as the BRSI. 40 images were visually evaluated for the presence of cortical bone porosity. The correlation between visual evaluation and BRSI of the participants, and the optimal threshold value of BRSI for new system were investigated through a receiver operator characteristic analysis. The diagnostic performance of the new system was evaluated by comparing the results from new system and lumbar bone density tests using 28 participants., Results: BRSI and lumbar bone density showed a strong negative correlation ( p < 0.01). BRSI showed a strong correlation with visual evaluation. The new system showed high diagnostic efficacy with sensitivity of 90.9%, specificity of 64.7%, and accuracy of 75.0%., Conclusions: The new screening system is able to quantitatively evaluate mandibular cortical porosity. This allows for preventive screening for osteoporosis thereby enhancing clinical prospects.

Objective: This randomized, clinical trial investigated whether zoledronic acid combined with oral health maintenance can improve periodontal disease associated with osteoporosis, thus reducing the risk of tooth loss., Methods: Participants were those of the ZONE (ZOledroNate treatment in efficacy to osteoporosis) study. None of the participants had symptomatic periodontal disease at baseline. Participants received either zoledronic acid (5 mg; n = 333 [male 21, female 312]) or placebo (n = 332 [male 19, female 313]) once yearly for 2 years, and their age was 74.0 ± 5.3 (65-88) and 74.3 ± 5.4 (65-87) years, respectively. Participants were instructed to maintain good oral hygiene at baseline and every 3 months. Participants with signs or symptoms involving their oral cavity at the monthly visit with their physician were referred to dentists for examination of oral disease. All cases were included to analyze adverse events in this study. Testing for significance was conducted using Fisher exact test (P < 0.05)., Results: The incidence of oral adverse events was significantly higher in the control group (67 cases, 20.2%) than in the zoledronic acid group (47 cases, 14.1%; P = 0.04). The frequency of symptomatic periodontal disease observed during the study was significantly higher in the control group (40 cases, 12.0%) than in the zoledronic acid group (18 cases, 5.4%; P = 0.002). Loss of teeth was more frequent in the control group (36 cases, 10.8%) than in the zoledronic acid group (24 cases, 7.2%), although the difference was not significant., Conclusions: Zoledronic acid effectively prevented symptomatic periodontal disease in patients with osteoporosis who maintained good oral hygiene. : Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A438.

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.

Background: Osteoporosis and cardiovascular disease are major public health problems. A number of clinical studies have shown a link between osteoporosis and cardiovascular disease, but there is no information on the associations of risk of osteoporotic fracture with vascular function and vascular structure.Methods and Results:The risk of major osteoporotic fracture was calculated using the World Health Organization fracture risk assessment tool (FRAX); vascular function was assessed using flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID), and vascular structure was assessed on brachial artery intima-media thickness (IMT) in 414 subjects (241 men and 173 women) who underwent health examinations. On univariate regression, FRAX was negatively correlated with FMD (total, r=-0.16, P<0.001; men, r=-0.19, P=0.003; women, r=-0.25, P<0.001) and NID (total, r=-0.22, P<0.001; men, r=-0.19, P=0.003; women, r=-0.30, P<0.001) and was positively correlated with brachial artery IMT (total, r=0.12, P=0.02; men, r=0.22, P<0.001; women, r=0.33, P<0.001). On multivariate analysis FRAX remained an independent predictor of FMD, NID, and brachial artery IMT in both men and women., Conclusions: Increase in the risk of osteoporotic fracture evaluated on FRAX is associated with vascular dysfunction and abnormal vascular structure in both men and women. Osteoporosis should be monitored in order to reduce the risk of cardiovascular events.

Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence., (Copyright © 2017. Published by Elsevier Inc.)

Objective: Our previous questionnaire-based survey suggested that discontinuation of antiresorptive agents before tooth extraction may increase adverse events and disturb osteoporosis treatment without completely preventing osteonecrosis of the jaw (O.N.J.). We also found little cooperation between physicians and dentists in Japan. However, limitations of our previous study included a survey of doctors belonging to small clinics and a small sample size. Our current study aimed to confirm the results of our previous survey in doctors mainly belonging to academia., Methods: A structured questionnaire including 14 key clinical queries was sent to 1812 physicians of the Japan Osteoporosis Society, and 629 responses were received., Results: Dentists requested discontinuation of many medications that were not associated with the incidence of O.N.J. A total of 523 respondents had received discontinuation requests from dentists. Of these, 97 respondents experienced 119 adverse events including 25 fractures and seven incidences of O.N.J. The ratios of valid responses for fractures were 3.6% and 5.3% in patients with a discontinuation of <3 and ≥3 months, respectively. Those for O.N.J. were 0.7% and 1.6%, respectively. Respondents who refused discontinuation requests reported no cases of O.N.J. Approximately 17% of respondents had patients who discontinued osteoporosis treatment following a requested drug discontinuation after tooth extraction. Approximately 62% of respondents did not request oral health care by a dentist before antiresorptive therapy, and 72% reported no cooperation between physicians and dentists in their region., Conclusions: This study reconfirms the results of our previous survey. Discontinuation of antiresorptive treatment may increase both fractures and O.N.J. Immediate development of a strategy for sharing information about O.N.J. among physicians, dentists, and patients is required to reduce the incidence of both O.N.J. and skeletal events in osteoporosis treatment. Study limitations were selection bias due to low response rate and possible inaccurate responses to the questionnaire.

Objectives: We investigated the association among diagnosed osteoporosis, osteoporotic fractures, and carotid artery calcification (CAC) detected on panoramic radiographs. Additionally, we assessed whether osteoporosis or fractures could be predicted by an incidental finding of CAC., Study Design: One thousand twenty-one patients participated in this study. Patients completed a structured questionnaire. Logistic regression analysis adjusted for covariates was used to calculate the odds ratio (95% confidence interval) for diagnosed osteoporosis or fractures according to the presence of CAC. Extended receiver operating characteristic (ROC) curve analysis was used to clarify whether osteoporosis or fractures were predicted by the detection of CAC., Results: The odds ratios for diagnosed osteoporosis or fracture associated with CAC were 1.82 (1.02-3.24) and 0.77 (0.33-1.77), respectively. The areas under the ROC curves for identifying patients with osteoporosis or fractures according to the detection of CAC were 0.54 and 0.50, respectively., Conclusions: CAC may not be useful for identifying Japanese individuals with osteoporosis or those at risk of fracture, although the presence of CAC was significantly associated with a history of diagnosed osteoporosis without osteoporotic fractures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-β ligand (RANKL). Previous reports have shown that denosumab treatment of osteoporotic patients decreases bone resorption and fracture risk, but there have been no clinical studies on changes in bone turnover markers, 1,25(OH)2D3, or parathyroid hormone (PTH) in denosumab therapy with or without bisphosphonate (BP) pre-treatment in Japan., Methods: Here, we report such findings in 22 patients (11 in the denosumab alone group and 11 in the BP pre-treated group) with osteoporosis following 4 months of treatment. Bone metabolism had been inhibited by prior BP administration in the BP pre-treated group., Results: The bone resorption markers serum tartrate-resistant acid phosphatase type 5b and urinary type I collagen cross-linked N-telopeptide were significantly decreased from baseline values for the entire study period in both groups. The bone formation marker bone alkaline phosphatase was significantly decreased at 4 months in the denosumab alone group only, and N-terminal propeptide of type 1 procollagen was significantly decreased at 2 and 4 months in the denosumab alone group versus no remarkable change in the BP pre-treated group. In the denosumab alone group, 1,25(OH)2D3 and PTH were significantly increased at 1 week and decreased gradually thereafter, but these did not change notably in the BP pre-treated group., Conclusions: Our results suggest that treatment with denosumab causes a strong inhibitory effect on bone resorption markers and mild inhibitory effect on bone formation markers. 1,25(OH)2D3 and PTH were significantly increased by denosumab but these did not change in the BP pre-treated group., Trial Registration: Current Controlled Trials NCT02156960. Registered 31 May 2014.

Alfacalcidol (ALF) and eldecalcitol (ELD) are vitamin D analogues that can be combined with anti-resorption drugs, such as bisphosphonate (BP) for the treatment of osteoporosis (OP). There has been no report comparing the effects of those vitamin D analogs in combination with BPs. Twenty female patients with OP were enrolled, and all of them were treated with ALF and BPs. After switching from ALF to ELD, we examined the effectiveness of ALF and ELD. The averaged age was 69.4 years and the period of BP usage was between 1 to 13.4 years (mean period was 3.7 years). Serum corrected calcium, serum inorganic phosphorus, serum bone specific alkaline phosphatase (BAP), and serum tartrate-resistant acid phosphatase (TRACP)-5b were measured prior to ELD and at 6 months afterwards. Bone mineral density (BMD) of the lumbar spine (L-BMD), femoral neck, and total hip BMD were assessed one year before, prior to, and one year after ELD therapy commencement. Six months after switching from ALF to ELD, BAP and TRACP-5b values significantly decreased. After one year of ALF therapy, L-BMD, total hip BMD and femoral neck H-BMD values slightly increased. In contrast, a year following the change from ALF to ELD, L-BMD significantly increased and femoral neck BMD slightly increased, but total hip BMD did not. These results suggest that the treatment with ELD after ALF significantly suppressed bone turnover and increased L-BMD. Thus, the combined therapy with ELD is more effective for OP treatment than that with ALF.

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.

Objective: The aim was to clarify the association between dental panoramic radiography measures of mandibular inferior cortical shape and biochemical markers of bone turnover in elderly men and women., Study Design: Subjects were 80-year-old men (n = 85) and women (n = 153). Mandibular cortical shape and width were evaluated on dental panoramic radiographs. Bone formation and resorption, respectively, were estimated by serum levels of carboxy-terminal propeptide of type I collagen (PICP) and serum type I collagen carboxy-terminal telopeptide (ICTP)., Results: Eroded cortices of the mandible were significantly associated with increased serum PICP levels (P = .005) in women. Lower mandibular cortical width quartiles were also significantly associated with increased serum PICP levels in men (P = .020) and women (P = .006)., Conclusions: Mandibular inferior cortical measures detected on dental panoramic radiographs may be associated with bone formation rates and be useful in predicting osteoporosis in elderly Japanese men and women.

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.

It is widely believed that the vasculature plays an important role in bone remodeling. We investigated the relationship between forearm endothelial function and bone mass in the lumbar spine in early postmenopausal women without a history of smoking or diabetes mellitus. We studied the forearm resistance artery endothelial function in 110 Japanese women-52 postmenopausal women with normal spinal bone mineral density (BMD), 36 postmenopausal women with osteopenia, and 22 osteoporotic postmenopausal women. Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin (NTG) administration was measured by strain-gauge plethysmography. BMD of the lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry. After adjustment for age, body mass index, years since the start of menopause, and basal FBF, women with osteoporosis had a lower maximal FBF response to reactive hyperemia (28.4 +/- 3.8 mL/min per 100 mL tissue) than those with normal BMD (39.8 +/- 2.8 mL/min per 100mL tissue) or osteopenia (35.6 +/- 2.5 mL/min per 100mL tissue) (P = 0.029). A significant increase in serum angiotensin-converting enzyme (ACE) activity (P = 0.042) and a significant decrease in the serum concentrations of nitrite/nitrate (P = 0.041) were noted in osteoporotic women compared to women with normal BMD or osteopenia. The present findings suggest that postmenopausal women with low BMD, especially those with osteoporosis, have impaired endothelial function in the forearm resistance arteries.

Osteoporosis affects large segments of elderly populations, especially postmenopausal women. Bone mineral density (BMD) assessment of the skeleton by means of several pieces of equipment, such as dual-energy X-ray absorptiometry, have been useful in identifying individuals with low BMD or at high risk of suffering osteoporotic fracture. Recent investigators have demonstrated a significant association between BMD of the mandible and the peripheral skeleton in postmenopausal women. Some studies also have linked low BMD of the mandible and the peripheral skeleton with alveolar bone loss of the mandible and tooth loss. Dental panoramic radiology is a useful imaging modality by which the dentist can evaluate the whole dentition as well as the jawbones. Clinicians have started to focus on some mandibular panoramic indices, such as mandibular cortical index and mandibular cortical thickness, for the identification of elderly individuals who should undergo BMD assessment. In comparison with peripheral BMD measurement equipment in the medical field, the dentist will be able to identify osteoporotic elderly individuals by means of dental panoramic radiographs taken for the diagnosis of the teeth and the jawbones without additional cost. It is likely that the clinician may estimate the future risk of tooth loss in elderly individuals with periodontitis and osteoporosis by dental panoramic radiographs.

The association between prevalent fractures and tooth loss in postmenopausal women remains unclear. Herein, we investigated the association between prevalent vertebral and nonvertebral fractures, the number of teeth present at baseline, and the number of teeth lost during follow‐up in postmenopausal Japanese women. This cross‐sectional study enrolled 843 participants (mean age 68.3 years). The number of teeth at follow‐up was evaluated in 655 women in this longitudinal study. The participants were divided into four groups according to their prevalent fracture status: no fractures, vertebral fractures alone, nonvertebral fractures alone, and both fracture types. After adjusting for covariates, Poisson regression analyses were performed to investigate differences in the number of teeth at baseline and that lost during the follow‐up period among the four groups. Participants with prevalent vertebral fractures alone had significantly fewer teeth at baseline than those in participants without fractures or nonvertebral fractures alone (p < 0.001 for both). Furthermore, they lost more teeth during the follow‐up period than did those with no fractures (p = 0.021) and tended to lose more teeth than did those with nonvertebral fractures alone or both prevalent fracture types. We observed no significant difference in the number of teeth lost between the participants with nonvertebral fractures alone and those with no fractures. Postmenopausal women with prevalent vertebral fractures may be at a higher risk of tooth loss. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [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]

Background: While it is well known that teriparatide (TPTD) increases bone mineral density (BMD) in osteoporotic patients, it is unknown whether TPTD pretreatment affects BMD after denosumab (DMAb) therapy.Methods: Fifty-seven patients in TPTD-pretreated group and 35 patients in DMAb-alone group had been further analyzed, all of whom were treated by DMAb for 1.5 years. Vitamin D (400 IU) and Ca (600 mg) supplementation was used in all patients. The BMD of lumbar 1-4 vertebrae (L-BMD), bilateral total hips (H-BMD), and bilateral femoral neck (FN-BMD) was quantified at first visit, and at 4, 8, 12, and 18 months after daily TPTD treatment following four times DMAb treatment.Results: There were significant differences in L-BMD (p=0.004) and H-BMD (p=0.026) at baseline between TPTD-pretreated and DMAb-alone groups, although there was no significant difference in FN-BMD between the two groups. The increase of L-BMD by DMAb therapy was less in TPTD-pretreated group than in DMAb-alone group. There was no significant difference in H-BMD, although percent changes of H-BMD tended to be higher in the TPTD-pretreated group than those in the DMAb-alone group. Percent change in FN-BMD at 4 months (p=0.067) and 12 months (p=0.057) tended to be higher in TPTD-pretreated group than in DMAb-alone group. Percent change in FN-BMD at 18 months was significantly higher in TPTD-pretreated group (p=0.004) than in DMAb-alone group.Conclusion: These findings suggest that the pretreatment of TPTD might have enhanced the increase of BMD in cortical bones treated by DMAb. Thus, it is favorable that TPTD can be used for osteoporotic patients who have high fracture risks with cortical bones. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the effects of denosumab in patients with osteoporosis (OP) and non-metastatic breast cancer following treatment of 1) surgery, 2) surgery and aromatase inhibitors, and 3) surgery, aromatase inhibitors, and anti-cancer agents, compared with those in primary OP patients. Patients and methods: In this retrospective 24-month study, patients were divided into the primary OP group (34 cases) or OP receiving breast cancer treatment group (breast cancer group; 17 cases). We measured serum calcium, whole parathyroid hormone (PTH), 1,25OH2D3, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and bilateral total hips (H-BMD) for 24 months. Results: The percent changes of serum calcium in the breast cancer group were significantly lower than those in the primary OP group at 1 week, 1 and 12 months. The percent changes of whole PTH in the primary OP group were significantly lower than those in the breast cancer group at 2 and 4 months. Significant differences were found between the groups at 18 months (-34.5% in the primary OP group and -52.6% in the breast cancer group, respectively) for the percent changes of BAP. Significant differences were found between the groups at 12, 18, and 24 months (-39.7% in the primary OP group and -64.0% in the breast cancer group at 24 months, respectively) for the percent changes of TRACP-5b. The percent changes of L-BMD and H-BMD were significantly increased at 12, 18, and 24 months in both the primary OP group (7.0% and 4.7% at 24 months, respectively) and breast cancer group (8.0% and 5.4% at 24 months, respectively), compared with pre-treatment levels. Significant differences were not found between the groups for the percent changes of L-BMD and H-BMD. Conclusion: Denosumab significantly increased L-BMD and H-BMD to comparable degrees in both groups; therefore, it represents a good therapeutic option for OP receiving breast cancer treatment as well as primary OP. Also, vitamin D supplementation is required due to the potential hypocalcemia, and estrogen may be responsible for the decrease of serum calcium in the breast cancer patients. [ABSTRACT FROM AUTHOR]

Summary: Numerous panoramic radiographs are taken annually to examine dental diseases, and using them for triaging individuals with general skeletal bone diseases, such as osteoporosis, would be economical and beneficial as dentists could refer these patients to medical professionals for further examination. Since the early 1990s, several studies have been performed regarding the utility of panoramic radiographs in triage screening for osteoporosis in dental clinics. Cortical indices of the mandible on panoramic radiographs, such as cortical width and cortical shape, are significantly associated with bone mineral density (BMD) of the general skeleton, biochemical markers of bone turnover and risk of osteoporotic fractures in postmenopausal women as well as elderly men. In prospective clinical trials, about 95% of postmenopausal women identified by trained general dental practitioners using cortical shape category on panoramic radiographs had low skeletal BMD or osteoporosis. Panoramic radiography indices may be likely useful triage screening tools for identifying individuals with an increased probability of having low skeletal BMD, osteoporosis and osteoporotic fractures. However, further investigations should be conducted worldwide to determine whether these indices are acceptable for triaging individuals with osteoporosis and referring them to medical professionals. [Copyright &y& Elsevier]