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To investigate the effects of high-intensity interval exercise training on microvascular endothelial function among community-dwelling older people.We analyzed the data from a nonrandomized controlled trial. This study's participants were 48 men (aged 75 ± 5 years; exercise training group, n = 24; control group, n = 24) and 83 women (aged 75 ± 4 years; exercise training group, n = 36; control group, n = 47). The exercise training group underwent a high-intensity interval walking training for 5 months.In the exercise group, 100% and 91.7% of men and women, respectively, achieved brisk walking times ≥50 min/week. The change in the reactive hyperemia index significantly differed between the groups of men, whereas that in the control group was not significant; however, a significant increase was observed in the exercise training group. Among women, changes in the reactive hyperemia index were not significant in either group; however, for women in the exercise training group, these changes negatively and positively correlated with the change in body mass index (Spearman's rho = -0.342; P = 0.041) and baseline body mass index (rho = 0.362, P = 0.030), respectively. Additionally, the distribution of body mass index was broader in women than in men.Interval walking training increased the reactive hyperemia index in men rather than in women. A higher variation in baseline body mass index may be associated with no statistical increase in reactive hyperemia index in women. Geriatr Gerontol Int 2023; ••: ••-••.

Second hip fractures worsen the quality of life and are associated with increased mortality. We clarified the association between the pharmacotherapy and second hip fracture prevention.The relationship between the incidence of second hip fracture and the presence, type and medication possession ratio (MPR) of pharmacotherapy was investigated using medical insurance data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan during April 2012 to March 2019.Data of 776 040 female patients were analyzed. The 2-year rate of second hip fractures was 3.31% (n = 25 684). Bisphosphonates (n = 148 138, 19.1%) were the most commonly used medications after primary hip fracture. Patients receiving selective estrogen receptor modulators (SERMs) had the lowest age, followed by those receiving bisphosphonates, denosumab and parathyroid hormone (PTH). The second hip fracture crude incidence was lowest in patients administered SERMs (n = 859, 2.44%), followed by those administered bisphosphonates (n = 4451, 3.00%), denosumab (n = 484, 3.19%), no medication (n = 19 017, 3.39%) and PTH (n = 873, 5.35%); however, the age-adjusted incidence was the lowest in patients administered denosumab (2.22%), followed by those administered bisphosphonates (2.35%), SERMs (2.39%), no medications (3.39%) and PTH (3.67%). The MPR was highest in patients administered denosumab (60.0%). Among patients without a second hip fracture, the rate of patients with MPR ≥80% was highest among those administered SERMs (40.8%), followed by those administered bisphosphonates (38.0%), denosumab (35.4%) and PTH (12.2%).Differences in patient background characteristics and the rate of patients with MPR ≥80% might underlie the observed differences in the crude incidence of second hip fracture among the medication groups. Geriatr Gerontol Int 2022; 22: 930-937.

The aims of this study were to investigate trends in bone mineral density (BMD) loss and related factors in early postmenopausal women in Japan, identify risk factors for future osteoporosis, and predict osteoporosis before it occurs.The study population consisted of women who were 50 to 54 years old at the time of the survey in 2002 or 2006. The study included a questionnaire and physical measurement findings (BMD, height, body weight [WT], body mass index [BMI], and handgrip strength). One hundred sixty-seven women continued to participate in the study and had BMD measurements at the 9- or 10-year follow-up of the Japanese Population-based Osteoporosis study. Statistical analyses were performed using Pearson correlation to examine each factor of physical measurement and BMD for lumbar spine (LS) and femoral neck (FN). The receiver operating characteristic curve of this data was also predictive of osteoporosis in 2011 for 2002 data; BMD at the age of 50 to 54 years was then used to predict the likelihood of being diagnosed with osteoporosis 9 and 10 years later.At the baseline in 2002 and 2006, WT, BMI, height, and handgrip strength were positively correlated with BMD. The optimal cutoff values for BMD in 2006 to predict osteoporosis in 2016 were LS less than 0.834 g/cm 2 and FN less than 0.702 g/cm 2 . These data were also predictive of osteoporosis in 2011 for 2002 data; applying this to the 2002 data, LS/FN had a sensitivity of 92%/100%, a specificity of 87%/81%, a positive predictive value of 55%/48%, and a negative predictive value of 98%/100%. The larger WT and BMI also resulted in a greater decrease in BMD of FN after 9 or 10 years.We have identified a cutoff value for BMD to predict future osteoporosis in menopausal women and found a negative correlation between WT and BMI in menopausal women and changes in BMD of the FN over the next 10 years.

The hypotensive effects of high-intensity interval training have been reported; however, studies on older adults are few. This study aimed to examine whether interval-walking training (IWT), a home-based programme of high-intensity interval training, reduces blood pressure (BP) levels when compared with a non-intervention group in community-dwelling older adults.An intervention study was conducted with 55 men (age, 75 ± 5 years; IWT/control groups, n = 27/28) and 100 women (75 ± 5 years; n = 47/53). The IWT regimen was as follows: fast (high-intensity) walking at 70%-85% of the peak aerobic capacity and normal (light-intensity) walking at approximately 40% of the peak aerobic capacity for 3 min each, ≥5 times/walking day, and ≥4 days/week for 5 months. Systolic, diastolic, and mean arterial BPs (SBP, DBP, and MAP, respectively) were measured in the supine posture.The mean baseline SBP/DBP was 132/78 mmHg in men and 131/72 mmHg in women. Five-month changes in SBP, DBP, or MAP did not significantly differ between the IWT and control groups in either sex. The weekly fast-walking time in the IWT group was negatively correlated with changes in DBP (Spearman's ρ = -0.383, p = 0.049) and MAP (ρ = -0.444, p = 0.021) only in men.Though present findings did not indicate significant hypotensive effects of IWT in community-dwelling older adults, men with longer fast-walking times experienced greater BP decreases. Further studies with sufficient sample sizes are needed to determine the factors modulating the effects of the proposed training programme.

Oral health is associated with atherosclerotic cardiovascular disease (ACVD). We previously identified the salivary microbiota characteristics of patients with ACVD. However, whether salivary microbiota is characteristic under impaired vascular endothelial function before ACVD onset remains unclear. Therefore, we aimed to evaluate the characteristics of salivary microbiota associated with peripheral microvascular endothelial dysfunction.We collected saliva samples from 172 community-dwelling elderly individuals without a history of ACVD and performed 16S rRNA metagenomic analysis. We assessed the peripheral microvascular endothelial function using reactive hyperemia index (RHI) and compared the salivary microbiota in the groups with normal (RHI ≥ 2.10), borderline, and abnormal (RHI ＜1.67) peripheral endothelial function. Furthermore, we applied machine learning techniques to evaluate whether salivary microbiota could discriminate between individuals with normal and abnormal endothelial function.The number of operational taxonomic units (OTUs) was higher in the abnormal group than in the normal group (p=0.037), and differences were found in the overall salivary microbiota structure (unweighted UniFrac distances, p=0.038). The linear discriminant analysis (LDA) effect size (LEfSe) algorithm revealed several significantly differentially abundant bacterial genera between the two groups. An Extra Trees classifier model was built to discriminate between groups with normal and abnormal vascular endothelial function based on the microbial composition at the genus level (AUC=0.810).The salivary microbiota in individuals with endothelial dysfunction was distinct from that in individuals with normal endothelial function, indicating that the salivary microbiota may be related to endothelial function.

The importance of oral health in type 2 diabetes mellitus (T2DM) is widely recognized; however, oral microbiota characteristics associated with T2DM in the elderly population are not well-understood. This study was conducted to evaluate the characteristics of the salivary microbiota in elderly Japanese patients with T2DM. Saliva samples were collected from 42 elderly Japanese patients with T2DM and 42 age- and sex-matched subjects without T2DM (control). 16S ribosomal RNA metagenomic analysis and comparative analysis of both groups were performed. Random forest classification by machine learning was performed to discriminate between the salivary microbiota in the two groups. There were significant differences in the overall salivary microbiota structure between the T2DM and control groups (beta diversity; unweighted UniFrac distances, p = 0.001; weighted UniFrac distances, p = 0.001). The phylum Firmicutes was abundant in patients with T2DM, whereas the phylum Bacteroidetes was abundant in controls. The T2DM prediction model by random forest based on salivary microbiota data was verified with a high predictive potential in five cross-validation tests (area under the curve (AUC) = 0.938 (95% CI, 0.824–1.000)). Characterization revealed that the salivary microbiota profile of the elderly patients with T2DM is significantly distinct from that of the controls. These data indicate the necessity of oral health management based on the characteristics of the salivary microbiota in elderly patients with T2DM. Our findings will contribute to future research on the development of new diagnostic and therapeutic methods for this purpose.

Areal BMD (aBMD) from DXA is not a sufficiently accurate predictor of fracture. Novel volumetric BMD derived from 3D modeling of the hip from DXA images significantly improved the predictive ability for hip fracture relative to aBMD at the femoral neck, but not aBMD at the total hip. To clarify whether volumetric and geometric indices derived from novel three-dimensional (3D) modeling of the hip using dual-energy X-ray absorptiometric (DXA) images improve hip fracture prediction relative to areal bone mineral density (aBMD). We examined 1331 women who had completed the baseline survey and at least one follow-up survey over 20 years (age 40–79 years at baseline). Each survey included aBMD measurement at the hip by DXA. Volumetric and geometric indices of the hip at baseline and the 10-year follow-up were estimated from DXA images using a 3D modeling algorithm. Incident hip fractures during the 20-year follow-up period were identified through self-report. Cox proportional hazards regression models allowing for repeated measurements of predictors and outcomes were constructed, and their predictive ability for hip fracture was evaluated using areas under receiver operating characteristic curves (AUCs) and net reclassification improvement (NRI) over aBMD at the femoral neck (FN) and total hip (TH) as references. During a median follow-up of 19.8 years, 68 incident hip fractures were identified (2.22/1000 person-years). A significantly larger AUC of trabecular volumetric BMD (vBMD) at the total hip (AUC = 0.741), femoral neck (AUC = 0.748), and intertrochanter (AUC = 0.738) and significant NRI (0.177, 0.149, and 0.195, respectively) were observed compared with FN-aBMD (AUC = 0.701), but not TH-aBMD. vBMD obtained from 3D modeling using routinely obtained hip DXA images significantly improved hip fracture risk prediction over conventional FN-aBMD, but not TH-aBMD. The Japanese Population-Based Osteoporosis (JPOS) Cohort Study was retrospectively registered as UMIN000032869 in the UMIN Clinical Trials Registry on July 1, 2018.

We aimed to clarify the risks of initiating antidiabetic drugs for fractures using a nationwide health insurance claims database (NDBJ).Patients aged ≥ 65 years initiating antidiabetic drugs at the outpatient department were enrolled after a 180-day period without prescribed antidiabetic drugs and followed with during 2012-2018 using NDBJ. The adjusted hazard risks (HRs) of each antidiabetic drug (thiazolidine, alpha-glucosidase inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, glinide, and insulin) for fractures compared with biguanide were obtained adjusting for age, gender, polypharmacy, dementia, and the other antidiabetic drugs.The DPP-4 inhibitor was the most often prescribed antidiabetic drug followed by biguanide with prescribed proportions of 71.7% and 12.9%. A total of 4,304 hip fractures and 9,388 vertebral fractures were identified among the 966,700 outpatient participants. Compared with biguanide, insulin, alpha-glucosidase inhibitor, and DPP-4 inhibitor were related to increased hip fracture risks. Vertebral fracture risk was higher in outpatients prescribed with insulin, thiazolidine, and DPP-4 inhibitor compared with biguanide. Patients prescribed insulin for hip and vertebral fractures' adjusted HRs were 2.17 (95% CI 1.77-2.66) and 1.45 (95% CI 1.24-1.70), respectively. Those prescribed DPP-4 inhibitor for hip and vertebral fractures' adjusted HRs were 1.27 (95% CI 1.15-1.40) and 1.20 (95% CI 1.12-1.28), respectively.Initiating insulin increased the risk of not only hip fractures but also vertebral fractures. Patients initiating antidiabetic drugs had increased risks of hip and vertebral fractures compared with those initiating biguanide independently for age, gender, polypharmacy, and dementia in the Japanese elderly.

Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to clarify the real-world effectiveness of AOMs against incident hip and vertebral fractures in patients undergoing GC therapy using the nationwide health insurance claims database of Japan (NDBJ).Patients aged ≥50 years who were prescribed GC (≥5 mg/day prednisolone or equivalent) for ≥90 days and who were followed up regarding AOM prescription and hip and clinical vertebral fracture incidences for the subsequent 1080 days between 2012 and 2018 were selected from NDBJ. Associations of AOMs prescribed within 90 days since GC therapy initiation with hip or vertebral fracture risk were evaluated by Cox proportional hazards regression using propensity score inverse probability weighting (IPW) for receiving any AOM or individual AOMs.In total, 96,475 women and 98,385 men were included in the analysis; 38.0 % of women and 27.6 % of men received AOMs. Patients who received any AOM and those who received bisphosphonates or denosumab had a significantly lower risk of hip and clinical vertebral fractures than those who received no AOM in both sexes after propensity score IPW. Teriparatide was associated with an increased risk of both fractures in women and an increased risk of clinical vertebral fractures in men. Selection biases such as confounding by indication might have caused an underestimation of AOMs' protective effects.Bisphosphonates and denosumab were associated with a lower fracture incidence in patients on long-term GC therapy in real-world settings.

Only a few large-scale studies have examined the care gap in Japan. The present study aims to examine the care gap for secondary fracture prevention. Changes in the rates of bone mineral density testing (test rate) and osteoporosis pharmacotherapy administration (treatment rate) before and after hip and vertebral fracture registration were examined based on medical insurance data from the medical care system for elderly individuals in Hokkaido, Japan, issued from July 2013 to December 2018. The hip fracture group comprised 18,258 women and 4162 men, whereas the vertebral fracture group comprised 34,907 women and 9958 men. Test rates were 0.2% and 1.4% prior to fracture registration (pre-registration) and 19.9% and 40.5% after fracture registration (post-registration) in the hip and vertebral fracture groups, respectively. Moreover, pre-registration treatment rates were 18.3% and 28.2% and post-registration rates were 32.7% and 61.0% in the hip and vertebral fracture groups, respectively. The vertebral fracture group had a significantly higher post-registration test and treatment rates than the hip fracture group. Moreover, the post-registration test and treatment rates in the hip fracture group tended to increase over the years. Both fracture groups showed a tendency for decreased post-registration test and treatment rates as age increased, with lower rates observed among men. Test and treatment rates after hip fracture registration remain lower compared with those after vertebral fracture registration. To bridge the care gap following fractures, medical professionals need better awareness regarding osteoporosis treatment for hip fractures among elderly individuals and males.

BACKGROUND The direct association between intake of Japanese fermented soybeans, namely natto, and bone mineral density (BMD) is known. However, the association with osteoporotic fractures has not been studied. OBJECTIVE This study aimed to investigate whether habitual natto intake is associated with a risk of osteoporotic fractures. METHODS This prospective cohort study included 1417 postmenopausal Japanese women who were enrolled in the Japanese Population-Based Osteoporosis cohort study in 1996, 1999, 2002, and 2006 and were aged ≥45 y at baseline. The intake of natto, tofu, and other soybean products was surveyed with use of a FFQ at baseline. Fractures were ascertained in follow-up surveys conducted in 1999, 2002, 2006, and 2011/2012. Osteoporotic fracture was the primary outcome and was defined as a clinical fracture occurring without strong external force, diagnosed with radiographs by a medical doctor. HRs with 95% CIs were estimated with Cox proportional hazard models. RESULTS During the 17,699 person-years of follow-up (median, 15.2 y), 172 women experienced osteoporotic fractures. After adjustment for age and BMD at the total hip, the HRs compared with those of

Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to examine whether physicians prescribe AOMs as soon as GC therapy is initiated, and whether a delay in AOM initiation affects hip and vertebral fracture incidence, using the nationwide health insurance claims database of Japan (NDBJ).Patients aged ≥50 years who were prescribed GC (≥5 mg/day prednisolone or equivalent) for ≥90 days and who were followed for AOM use and hip and vertebral fracture events for the subsequent 1080 days in 2012-2018 were selected from NDBJ. Delay in AOM initiation was defined as the number of days without AOMs following GC therapy initiation. Associations between delay in AOM initiation and hip and vertebral fracture risk were evaluated by Cox proportional hazards regression.In total, 92,143 women and 94,772 men were included in the analysis, of which only 39.3% of women and 28.5% of men received AOMs within 90 days from GC therapy initiation. Approximately, 15% of hip fractures and 30% of vertebral fractures occurred before AOM initiation in patients with delayed AOM initiation. HRs of both fractures were significantly greater in patients with a longer delay in AOM initiation (p value for trend0.001). After excluding patients who had fractures before AOM initiation, the magnitude of HRs significantly decreased, and HR trends for hip fracture became insignificant.Delayed initiation of AOMs may result in increased fracture events, which may be reduced by early initiation of AOMs.

In Japan, persistence and the 2-year MPR were inadequate in increasing fracture control efficacy despite a high adherence rate during the treatment period. Both factors were higher in females and those with polypharmacy but worsened with increasing age. Only a few large-scale studies have examined the care gap between the patients who need osteoporosis treatment and those who receive them in Japan. The aim of this study was to investigate the persistence and adherence to osteoporosis pharmacotherapy in Japan. Continuation (persistence) rates and adherence to osteoporosis pharmacotherapy were investigated using medical insurance data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, between April 2012 and March 2019. The study included 528,806 male and 3,064,410 female patients. Persistence proportions were 56.6% in the first year and 46.3% in the second year. The medication possession ratio (MPR) from start to discontinuation of treatment (MPRdiscon) was 94.5%, and 92.7% of patients had an MPRdiscon ≥ 80%. The 2-year MPR (MPR730) was 61.9%, and 49.6% of patients had an MPR730 ≥ 80%. Both the persistence proportion and MPR730 were higher in females than in males, whereas MPRdiscon was higher in males. The persistence proportion and MPR730 were highest in the 70–79 years age group, whereas MPRdiscon improved with increasing age. The MPRdiscon and MPR730 were higher in the mixed-fracture and vertebral-fracture groups, respectively. The persistence proportion, MPRdiscon, and MPR730 were higher in patients with polypharmacy than in those without. In Japan, persistence and the 2-year MPR were inadequate in increasing fracture control efficacy despite a high adherence rate during the treatment period. To bridge the care gap following osteoporosis pharmacotherapy, improvements are required for males, the elderly, and those without polypharmacy.

Objectives To investigate the association between hand-grip strength and site-specific risks of major osteoporotic fracture. Study design Prospective cohort study. Main Outcome Associations between low hand-grip strength and increased risk of fracture at the distal forearm, vertebrae, and hip. Measures We enrolled 1342 postmenopausal women aged 50 years or more into baseline and follow-up surveys of the Japanese Population-based Osteoporosis Cohort Study in 1996, 1999, 2002, or 2006. Fracture events were ascertained by follow-up surveys until 2011 or 2012. The Cox proportional hazards model was used to estimate hazard ratios (HRs) of hand-grip strength on fracture event. Results During a median follow-up of 15.2 years, 162 women sustained at least one osteoporotic fracture and 135 of these women sustained at least one major osteoporotic fracture, the larger group including 65, 38, 35, and 8 women with fractures of the distal forearm, vertebrae, hip, and proximal humerus, respectively. In the crude models, the associations between low hand-grip strength and increased risk of fracture at the distal forearm, vertebrae, and hip were significant; the HRs (95% confidence interval) of the lowest tertile of hand-grip strength were 2.02 (1.10–3.71), 11.35 (4.07–31.63), and 4.72 (1.79–12.47), respectively. Age adjustment attenuated the significance of hip fracture risk, and adjusting for bone mineral density attenuated the significance of distal forearm fracture risk. After additional adjustment for body mass index, history of diabetes mellitus, and calcium intake, the HR for vertebral fracture risk was 4.55 (1.56–13.27). When limiting the follow-up period to 5 and 10 years, low hand-grip strength was associated with an increased risk of distal forearm fracture independently of the aforementioned covariates; the HRs were 4.22 (1.12–15.95) and 2.52 (1.03–6.17), respectively. Conclusions Low hand-grip strength is specifically associated with the risk of distal forearm fractures within 10 years and clinical vertebral fractures within 15 years or more in Japanese postmenopausal women.

Purpose Many studies have reported that patients with a history of gastrectomy (gastrectomized patients) have lower areal bone mineral density (aBMD) and higher fracture risk than those without. However, population-based studies on this topic are scarce, and little is known regarding the bone metabolic status of gastrectomized patients in the long-term. This study aimed to clarify the association of gastrectomy with aBMD, bone metabolism markers, and fracture risk in community-dwelling elderly Japanese men. Methods A total of 1992 men aged ≥65 years completed baseline measurements including aBMD at the spine and hip, serum levels of intact parathyroid hormone (PTH), intact osteocalcin (OC), tartrate-resistant acid phosphatase isoenzyme 5b (TRACP5b), and undercarboxylated OC (ucOC), and an interview regarding past medical history including gastrectomy. Osteoporotic fractures (OPFs) that occurred during the 5-year follow-up period were determined through structured interviews. Results After excluding participants with type 1 diabetes mellitus and those with missing values, 1985 men, including 132 gastrectomized men, were analyzed. Gastrectomized men had significantly higher PTH, TRACP5b, and ucOC levels, and lower aBMD, than non-gastrectomized men. Gastrectomy was associated with a significantly higher risk of OPF after adjusting for confounding variables (hazard ratio (HR): 2.55, 95% confidence interval (CI): 1.17, 5.55), and the risk was no longer significant when further adjusted for PTH and aBMD. Even in this model, however, increase in OPF risk was significant in gastrectomized men who survived 20 years or more after the surgery (HR: 3.56, 95% CI: 1.33, 9.52). Conclusions History of gastrectomy was associated with elevated bone resorption, decreased aBMD, and increased fracture risk in community-dwelling elderly Japanese men. This increase in fracture risk was more prominent long after gastrectomy.

Using the nationwide health insurance claims database, we found that the age-standardized hip fracture incidence rates in Japan indicated significant increase in males but no significant change in females during 2012–2015. The fracture risk in subjects aged 75–84 years indicated decrease in females but no change in males. Nationwide registry data on hip fractures have not yet been established in Japan. Using the newly developed National Database of Health Insurance Claims (NDB), which covers the entire Japanese population, we investigated the incidence rates of hip fractures and the associated regional differences. We also assessed the frequency of osteoporosis prescriptions, bone turnover marker (BTM) level, and bone mineral density (BMD) measurements. The annual numbers of hip fractures, osteoporosis prescriptions, and BTM level and BMD measurements by prefecture from 2012 to 2015 were obtained from NDB data. We calculated the standardized claims-data ratio (SCR) in each prefecture. The age-standardized incidence rates from 2012 to 2015 indicated no significant change in females and significant increase in males (p value for trend; 0.920, 0.002, respectively). The fracture risk decreased in females aged 75–84 years and indicated no increase in females aged 85–89 years during 2012–2015, while the fracture risk indicated no change in males aged 75–84 years and increased in males aged 85–89 years. The frequency of osteoporosis prescriptions, BTM level measurements, and BMD measurements in the general population in the corresponding period increased with statistical or marginal significance in females and males. West–east regional differences were observed in the incidence rates; the highest SCR values in the western prefectures were approximately double the lowest values in the eastern prefectures. The age-standardized hip fracture incidence rates indicated no significant change in females and significant increase in males in Japan from 2012 to 2015.

Background Several studies have examined the association between physical performance and fracture in women, but few such studies have targeted elderly men. This study aimed to determine whether the combined results of several physical performance tests can predict the subsequent incidence of fractures in elderly men after adjusting for confounding factors. Methods Of the 2174 elderly men who participated in this study, 2012 completed the baseline study visit, including physical performance tests (walking speed, hand grip strength, and one-leg standing) and measurement of bone mineral density by dual-energy X-ray absorptiometry. Follow-up study visits were conducted five and ten years later, during which incident fractures were identified by detailed interviews. We excluded 140 men with diseases or who took medications known to affect bone metabolism at baseline, 185 with missing values for predictors and potential confounding factors, and one who did not participate in any of the follow-up study visits. The remaining 1686 men were analyzed. Each physical performance test was analyzed by quartiles. Poor performance was defined as belonging to the worst quartile of performance. The association between physical performance and fracture was assessed using Cox proportional hazards models. Results We identified 175 clinical fractures (osteoporotic fracture: 77, major osteoporotic fracture: 48) in 1686 men during a mean follow-up period of 8.4 years. After adjusting for potential confounding factors including bone mineral density, men who performed poorly on all three physical performance tests had a 3.7-fold higher risk of osteoporotic fracture and a 6.6-fold higher risk of major osteoporotic fracture than men who did not perform poorly on any of the tests. Conclusions Japanese elderly men who performed poorly on all three physical performance tests had a significantly higher risk of incident osteoporotic fracture independently of bone mineral density. The combined results of several physical performance tests may be useful for predicting incident fractures in elderly men.

Background Body mass-independent parameters might be more appropriate for assessing cardiometabolic abnormalities than weight-dependent indices in Asians who have relatively high visceral adiposity but low body fat. Dual-energy X-ray absorptiometry (DXA)-measured trunk-to-peripheral fat ratio is one such body mass-independent index. However, there are no reports on relationships between DXA-measured regional fat ratio and cardiometabolic risk factors targeting elderly Asian men. Methods We analyzed cross-sectional data of 597 elderly men who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study, a community-based single-center prospective cohort study conducted in Japan. Whole-body fat and regional fat were measured with a DXA scanner. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. Results Both TAR and TLR in the group of men who used ≥ 1 medication for hypertension, dyslipidemia, or diabetes (“user group”; N = 347) were significantly larger than those who did not use such medication (“non-user group”; N = 250) (P < 0.05). After adjusting for potential confounding factors including whole-body fat, both TAR and TLR were significantly associated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, fasting serum insulin, and the insulin resistance index in the non-user group and non-overweight men in the non-user group (N = 199). Conclusion The trunk-to-peripheral fat ratio was associated with cardiometabolic risk factors independently of whole-body fat mass. Parameters of the fat ratio may be useful for assessing cardiometabolic risk factors, particularly in underweight to normal-weight populations.

Test and treatment rates for osteoporosis in Japan aimed at preventing secondary fragility fractures were insufficient. Those who suffered hip fractures had approximately half the rates of those who suffered vertebral fractures, with such rates being lower among those over 80 years old and males. The present study aimed to examine the care gap for secondary fracture prevention in Japan given the few large-scale studies regarding the matter. Changes in bone mineral density testing (test rate) and osteoporosis pharmacotherapy administration (treatment rate) rates before and after hip and vertebral fracture registration were examined using medical insurance data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan issued from April 2012 to March 2019. The hip fracture group comprised 677,480 women and 264,003 men, the vertebral fracture group comprised 703,247 women and 251,542 men, and the mixed fracture group comprised 3614 women and 1055 men. Test rates were 14.1%, 25.3%, and 17.6% prior to fracture registration (pre-registration) and 22.3%, 43.6%, and 28.1% after fracture registration (post-registration) in the hip, vertebral, and mixed fracture groups, respectively. Moreover, pre-registration treatment rates were 21.2%, 33.5%, and 30.7%, while post-registration rates were 31.6%, 61.7%, and 46.6% in the hip, vertebral, and mixed fracture groups, respectively. All fracture groups showed a tendency for decreased post-registration test and treatment rates among those aged over 80 years old, with men having lower rates. Moreover, 184,180 (19.4% of whom received new treatment) and 707,263 (23.8% of whom received new treatment) patients with and without polypharmacy underwent treatment after registration, respectively. To bridge the care gap following fractures, medical professionals should change their perception regarding osteoporosis treatment in patients with hip fractures, elderly individuals undergoing polypharmacy, and males.

Aims Oral bacteria have been reported to be associated with the pathogenesis of atherosclerosis; however, the relationship between the oral microbiota and atherosclerosis remains unclear. The present study aimed to investigate whether or not salivary microbiota of patients with atherosclerotic cardiovascular disease (ACVD) differs from that of subjects without ACVD, and to characterize the salivary microbiota of patients with ACVD. Methods This study included 43 patients with ACVD and 86 age- and sex-matched non-ACVD individuals. 16S rRNA metagenomic analysis were performed using DNA isolated from the saliva samples of the participants. To select unique operational taxonomic unit (OTU) sets of ACVD, we conducted the random forest algorithm in machine learning, followed by confirmation via 10-fold cross-validation Results: There was no difference in richness or evenness between the ACVD and non-ACVD groups (alpha diversity; observed OTU index, p=0.503; Shannon's index, p=0.478). However, significant differences were found in the overall salivary microbiota structure (beta diversity; unweighted UniFrac distances, p=0.001; weighted UniFrac distances, p=0.001). The Actinobacteria phylum was highly abundant in patients with ACVD, while the Bacteroidetes phylum was less abundant. The random forest classifier identified 43 OTUs as an optimal marker set of ACVD. In a 10-fold cross validation using the validation data, an area under the curve (AUC) of 0.933 (95% CI, 0.855-1.000) was obtained. Conclusions The salivary microbiota in patients with ACVD was distinct from that of non-ACVD individuals, indicating that the salivary microbiota may be related to ACVD.

Introduction Cross-sectional studies have shown that patients with type 2 diabetes mellitus (T2DM) have low circulating levels of osteocalcin (OC) and undercarboxylated OC (ucOC). This longitudinal study aimed to examine whether low OC or ucOC levels at baseline are associated with the risk of incident T2DM. Methods We examined 1700 community-dwelling Japanese men (≥65 years) after excluding those with history of diseases (other than T2DM) or medications that affect bone and glucose metabolism. T2DM was defined as fasting plasma glucose (FPG) ≥126 mg/dl or glycated hemoglobin A1c (HbA1c) ≥6.5%. Participants without prevalent T2DM at baseline were invited to follow-up surveys 5 and 10 years after baseline. Results Among the participants, 309 with prevalent T2DM showed significantly lower serum OC and ucOC levels at baseline than those without. After excluding these participants, 46 and 57 participants with incident T2DM were identified in the first and second follow-up surveys, respectively. These participants did not show significantly different OC and ucOC levels at baseline relative to those without T2DM, although their FPG and HbA1c levels at baseline were significantly higher compared to those without incident T2DM. Increase in glycemic indices preceded decrease in OC and ucOC levels. OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM identified in the follow-up surveys. Conclusions OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM. Our results do not support the findings of animal studies that ucOC is a hormone regulating glucose metabolism.

Only a few large-scale studies have examined the care gap in Japan. The aim of this study was to investigate the persistence of and adherence to osteoporosis pharmacotherapy in Japan. The rates of continuation (persistence) of and adherence to osteoporosis pharmacotherapy were investigated using medical insurance data, issued from July 2013 to December 2018, from the medical care system for elderly individuals in Hokkaido, Japan. The study included 7918 male and 52,585 female patients. Persistence rates were 62.1% in the first year and 45.3% in the second year. There were 33,096 patients who discontinued medication; 8296 patients resumed medication during the observation period of 730 days. The median time to the discontinuation of medication for all the patients was 702 days. The 2-year medication possession ratio (MPR) was 63.8%; 30,989 patients (51.2%) had an MPR ≥ 80% and 20,788 (34.4%) had an MPR

Purpose The association between serum concentrations of uric acid (UA), a potent endogenous antioxidant, and fracture risk has not yet been examined for morphometric vertebral fracture (VF). This study aimed to determine whether serum UA concentrations are associated with risks of clinical osteoporotic fracture (OPF) and morphometric VF after adjusting for confounding factors including UA-lowering medications (ULMs). Materials and methods A total of 2012 Japanese men aged ≥65 years completed the baseline study, which included serum UA measurement and X-ray absorptiometry-based VF assessment. We conducted a follow-up study five years later to identify incident OPFs and VFs. OPF was identified through interviews. Incident VF was defined as a vertebra which showed reduction in any of its anterior, central, or posterior heights by ≥20% during follow-up, and satisfied grade one or higher fracture criteria in Genant's method on follow-up images. Bone mineral density (BMD) of the hip and spine was measured by dual-energy X-ray absorptiometry at baseline and follow-up. Results We identified 45 clinical OPFs from 2000 men and 39 VFs from 1530 men during a mean follow-up period of 4.3 years. Hip BMD was significantly higher in higher UA concentration groups after adjusting for age and body mass index. A significantly decreased multivariate-adjusted odds ratio (OR) of incident VF was observed for the highest quartile groups of serum UA concentrations compared with the lowest quartile group (OR: 0.17, 95% confidence interval: 0.05–0.62). This OR remained significant after further adjusting for ULM use. ULM users in the lowest quartile group of serum UA concentrations had a significantly higher incidence rate of VF compared to the other quartile groups. Conclusions Higher serum UA concentrations were associated with a lower risk of morphometric VF independently of ULM in Japanese elderly men. Excessive reduction of serum UA concentrations by ULM might increase VF risk.

This study examined whether bone microarchitecture determined by Trabecular Bone Score (TBS) is associated with the risk of major osteoporotic fractures independent of FRAX® in Japanese women. Participants included 1541 women aged ≥ 40 at baseline. Major osteoporotic fractures during a 10-year follow-up period were documented by the Japanese Population-based Osteoporosis Cohort Study. TBS and areal bone mineral density (aBMD) were calculated for the same spinal regions at baseline. To compare the predictive ability of FRAX® model when used alone versus in combination with TBS, Akaike information criterion (AIC), the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated. We identified 67 events of major osteoporotic fractures. The skeletal sites of the first fracture event were as follows: hip (11), vertebrae (13), radius (42), and humerus (1). The model incorporating FRAX® [1.35 (95% CI 1.09–1.67) for 1 standard deviation (SD) increase] with TBS [1.46 (95% CI 1.08–1.98) for 1 SD decrease] demonstrated better fit compared to a model consisting of FRAX alone (AIC 528.6 vs 532.7). NRI values for classification accuracy showed significant improvements in the FRAX® and TBS model, as compared to FRAX® alone [0.299 (95% CI 0.056-0.541)]. However, there were no significant differences in AUC or IDI between these models. The TBS score is associated with a risk of major osteoporotic fracture independent of FRAX® score obtained with or without BMD values among Japanese women during a 10-year follow-up period.

Background Fibroblast growth factor 23 (FGF23) induces cardiac remodeling. We investigated the changes in serum FGF23 levels in patients diagnosed with acute myocardial infarction (AMI).Methods and Results:A total of 44 patients diagnosed with AMI were included in the current study. All patients underwent emergency percutaneous coronary intervention (PCI). The median of peak creatine kinase (CK) and CKMB values was 1,816 U/L and 159 U/L, respectively. Serum levels of FGF23, calcium, and inorganic phosphate (iP) were measured before PCI, and on days 1, 3, 5, 7 after PCI. Serum FGF23 levels showed a slight, but significant decrease on days 1 and 3 after PCI, and a 1.5- and 2.0-fold increase on days 5 and 7, respectively, after PCI. As compared with propensity score-matched patients without AMI, serum FGF23 was significantly lower among the current cohort of AMI patients. In 22 subjects who underwent a follow-up echocardiographic examination at 6 months after the onset of AMI, the log-transformed relative increase in FGF23 on day 7 significantly and negatively correlated with changes between LVEF on admission and that at 6 months afterward. Conclusions After a slight decrease on days 1 and 3 after admission, serum FGF23 increased significantly on days 5 and 7. The underlying mechanism and potential clinical importance of these observations require further investigation.

There are conflicting reports on whether muscle strength is associated with bone mineral density (BMD) independently of muscle mass. Here, we examined the association between muscle strength and BMD in a representative population of Japanese women. Cross-sectional data from 680 postmenopausal women, who were participants in the 15th-year follow-up survey of the Japanese Population-based Osteoporosis cohort study, were analyzed. Areal BMD (aBMD) at the femoral neck and lumbar spine, whole-body bone mineral density, and appendicular skeletal muscle mass (ASM, kg) were measured by dual-energy X-ray absorptiometry. The ASM index (ASMI, kg/m2) was calculated as ASM divided by height squared (m2). Grip strength (kg) was measured as an indicator of muscle strength. Grip strength showed significantly (P

Purpose Patients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association. Methods A total of 2012 community-dwelling men aged ≥ 65 years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history. Homeostasis model assessment-insulin resistance (HOMA-IR) was also calculated. T2DM was defined as physician-diagnosed middle age or elderly-onset diabetes mellitus, or according to biochemical test results. To evaluate bone microarchitecture, trabecular bone score (TBS) was calculated at the same vertebrae as those used for aBMD measurement. Results After excluding participants who had a disease history and/or were taking medications affecting bone metabolism, 1683 men (age, 72.9 ± 5.2 years) were analyzed. Men with T2DM had significantly higher aBMD compared to those without T2DM. There was no significant difference in TBS. However, FPG, HbA1c and HOMA-IR levels were significantly inversely correlated with TBS after adjusting for age, BMI and aBMD. Multivariate linear regression analyses revealed that glycemic indices (FPG and HbA1c) were significantly associated with increased aBMD and decreased TBS, and that HOMA-IR was associated only with TBS. These associations did not change after further adjusting for bone turnover makers and pentosidine levels. Conclusions Hyperglycemia and elevated insulin-resistance were associated with low TBS independently of bone turnover and pentosidine levels.

Context Although the endogenous secretory receptor for advanced glycation end products (esRAGE) has been associated with reduced activity of pentosidine (PEN), the association between PEN, esRAGE, and fracture is poorly understood. Objectives To evaluate the ability of serum PEN and esRAGE levels to predict fragility fractures. Methods A cohort of 1285 Japanese men aged ≥65 years old participated in a 2007 to 2008 Fujiwara-kyo Osteoporosis Risk in Men study baseline survey, as part of the Fujiwara-kyo prospective cohort study. Those participants provided information regarding any fractures they experienced during 5 years. The baseline bone mineral density (BMD) was measured. Hazard ratios (HRs) per one standard deviation increase of log-transformed serum levels of PEN, esRAGE, and esRAGE-to-PEN ratio were estimated at baseline. Results Twenty-five participating men suffered incident clinical fragility fractures. The crude HRs (95% confidence interval) for PEN, esRAGE, and esRAGE-to-PEN ratio were 1.56 (1.05 to 2.31), 0.79 (0.54 to 1.15), and 0.65 (0.44 to 0.95), respectively. HRs for PEN adjusted for age, esRAGE, and T score of BMD at femoral neck (FN) and lumbar spine (LS) were 1.48 (1.00 to 2.18) and 1.51 (1.03 to 2.21), respectively. The marginal significance adjusted for BMD at FN and the statistical significance adjusted for BMD at LS were attenuated after additional adjustment for glycated hemoglobin A1c level (P = 0.111 and 0.072, respectively). The HRs for esRAGE-to-PEN ratio adjusted for age, glycated hemoglobin A1c, and T-score of BMD at FN and LS were 0.67 (0.45 to 0.98) and 0.64 (0.43 to 0.95). Conclusions Higher esRAGE-to-PEN ratios were associated with decreased risk of fragility fractures independent of BMD among elderly Japanese men.

2016年 3 月、発表された日本版ガストロノミーイニシアティブ構想案において「ガストロノミーの定義」が訳出されている。だが実際には、日本でのガストロノミーの研究は希少であり、語彙としても馴染みが薄く社会に浸透していない。一方構想案におけるこの概念は、今後の日本の観光開発における主要な概念であることに疑いの余地はない。そこで、観光者も含めたこの概念に対する相互的理解とそれに向けての盤石な理論的構築が必要であると考える。本稿においては、ブリア＝サヴァランの「ガストロノミーの定義」における本義を探り、加えて、ガストロノミーに包摂されるいくつかの外苑を探求し精査する。そのことを以て、ガストロノミーをより考察されたものにしようと試みる。

We found that community-dwelling women with 25-hydroxyvitamin D levels

In epidemiological studies, there is little evidence regarding the relative impact of central adiposity and peripheral adiposity on cardiometabolic risk factors, especially in Asian populations. This study investigated associations between central-to-peripheral fat ratios and cardiometabolic variables using data from a population-based study of Japanese women. The source population was composed of 1800 women aged 50 yr or older at the 15th- to 16th-yr follow-up survey of the Japanese Population-Based Osteoporosis Cohort Study. This study analyzed cross-sectional data from 998 women for whom complete information about body fat variables according to dual-energy X-ray absorptiometry, cardiometabolic variables, and potential confounding factors was available. Both before and after adjusting for potential confounding factors, trunk-to-appendicular fat ratios showed significant (p

Objectives To investigate whether low bone mineral density (BMD) and history of fracture at baseline are associated with the development of echogenic carotid plaques over a 10-year follow-up period. Study design A prospective cohort study. Main outcome measures Development of echogenic plaques identified by ultrasonography of the carotid arteries. Methods Among 1048 women aged 40 or more who completed the baseline survey of the Japanese Population-based Osteoporosis (JPOS) cohort study, 500 women who completed the first decade of follow-up and 267 women who completed the second decade of follow-up were included. We identified history and incidence of clinical osteoporotic fracture during the follow-up through medical interviews, and determined vertebral fractures by morphometry of absorptiometric images. Results We identified 67 (13.4%) and 31 (11.6%) women with echogenic plaques at the end of first and second decade of follow-up, respectively. Participants with echogenic plaques were significantly older, exhibited lower spine BMD, and had a higher prevalence of osteoporotic fracture, diabetes, and hypertension. A generalized estimating equation analysis was used to combine the participants from the two follow-up periods into a single cohort, and showed that osteoporotic BMD and osteoporotic fractures were significantly associated with the development of echogenic plaques, after adjusting for atherosclerosis risk factors (odds ratio (OR): 2.15, 95% confidence interval (95% CI): 1.04, 4.44; OR: 1.84, 95% CI: 1.03, 3.28, respectively). Conclusion Osteoporotic BMD and osteoporotic fracture history were significantly, and independently, associated with an increased occurrence of echogenic plaques. Ultrasonographic screening of the carotid artery may benefit patients with osteoporosis.

現代のイタリアにおける農村観光には、ガストロノミーの概念が深く関わっている。観光者の明確な旅の目的が、食の味覚に関わるガストロノミック体験にあるからだ。食の味覚とは紛れもない生産地の美味であり、味覚の基準は法規で明瞭化されている。すなわち、農村観光とは、味覚の固有性と真正性を基盤に構築された新しいツーリズムのパラダイムであると考えられる。こうしたパラダイムとガストロノミーの概念との関係性は、実は二千数百年以上も前に明示されていたと考えられる。古代ギリシャ時代に提起されたガストロノミーの要素を探るために、紀元前4世紀半ば頃に記されたアルゲストラートの詩編を分析し検討した。そのことにより、提要されたガストロノミーの要素が、現代のイタリアにおける農村観光の発展に関わる要須な概念の起源であることを探求した。

【Objectives】Because of the declining birthrate in Japan, an increasing number of companies are hiring immigrants to fill the labor shortage. Although research on migrant occupational health has progressed in the United States, this topic has received little attention in Japan. The aim of this study was to elucidate the current situation, challenges, and solutions surrounding the occupational health of immigrant workers in the United States. 【Methods】Data and selected studies were reviewed and analyzed. The results are discussed, and a few anecdotal experiences in the United States are introduced and compared. 【Results】Possible causes of disparities in immigrant occupational health fell into the following seven categories. (Keywords for each category are shown in parentheses.) (1) Occupation (hazardous job, injury, missed workday, blue-collar worker, low birth weight); (2) Education (academic record, health literacy, training); (3) Culture (culture-specific, community-based); (4) Environment (poor hygiene, regional disparities, environmental change); (5) Access (language, statistics, workers' compensation, health insurance, voluntary restraint); (6) Infection (tuberculosis, human immunodeficiency virus/AIDS, follow-up); and (7) Discrimination (race, assault, harassment). Lack of data on immigrant workers was found to be a common problem. Some businesses and community groups achieved positive results by simultaneously dealing with multiple aforementioned categories. 【Discussion】In the United States, the occupational health of immigrant workers has been studied mainly in terms of health disparities. Possible causes of disparities in immigrant occupational health fell into seven categories. Solutions centered on the keywords in each category were inferred. Some businesses and community groups achieved positive results by simultaneously dealing with multiple aforementioned categories. Occupational health professionals have to take each of seven categories into account to improve immigrant occupational health. Even the United States-a developed country facing many migrant occupational health problems-needs further research and better data. To address this issue in Japan, we too need more data and further research on immigrants, along with efforts by businesses and community groups. Language: en

Patients with type 2 diabetes mellitus have an increased fracture risk. However, population-based studies on the association between glycemic status and fracture risk are scarce, and none have targeted a Japanese population. In addition, patients in the lowest category of hemoglobin A1c (HbA1c) do not always show the lowest risk. This study aimed to clarify the association between glycemic status and fracture risk in community-dwelling elderly Japanese men.A total of 1992 men aged ≥65 years completed baseline measurements including fasting plasma glucose (FPG), HbA1c, bone density, and an interview regarding past disease history. Osteoporotic fractures (OPFs) that occurred during the 5-year follow-up period were determined through interviews. An OPF at the spine, hip, proximal humerus, or distal radius was defined as a major OPF (MOF).After excluding participants who had a history of type 1 diabetes mellitus and thiazolidinedione therapy, 1951 men were analyzed. Men with hyperglycemia in the diabetic range had a significantly higher risk of OPF compared with those with normoglycemia, after adjusting for confounding factors including insulin therapy (hazard ratio (HR): 2.76, 95% confidence interval (CI): 1.17, 6.50 in FPG ≥ 126 mg/dl; HR: 2.49, 95% CI: 1.07, 5.77 in HbA1c ≥ 6.5%). An elevated risk of MOF was observed in participants in the prediabetic HbA1c category (HR: 2.15, 95% CI: 1.00, 4.62 in 5.7% ≤ HbA1c 6.5%) in addition to those in the diabetic category. The intermediate glycemic status group showed intermediate risk, suggesting that the association was linear.Hyperglycemia was associated linearly with elevated fracture risk in community-dwelling elderly men. MOF risk may be elevated in Japanese elderly men with prediabetic glycemic status.