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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.

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.

Background The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study was launched to investigate risk factors for osteoporotic fractures, interactions of osteoporosis with other non-communicable chronic diseases, and effects of fracture on QOL and mortality. Methods FORMEN baseline study participants (in 2007 and 2008) included 2012 community-dwelling men (aged 65–93 years) in Nara prefecture, Japan. Clinical follow-up surveys were conducted 5 and 10 years after the baseline survey, and 1539 and 906 men completed them, respectively. Supplemental mail, telephone, and visit surveys were conducted with non-participants to obtain outcome information. Survival and fracture outcomes were determined for 2006 men, with 566 deaths identified and 1233 men remaining in the cohort at 10-year follow-up. Comments The baseline survey covered a wide range of bone health-related indices including bone mineral density, trabecular microarchitecture assessment, vertebral imaging for detecting vertebral fractures, and biochemical markers of bone turnover, as well as comprehensive geriatric assessment items. Follow-up surveys were conducted to obtain outcomes including osteoporotic fracture, cardiovascular diseases, initiation of long-term care, and mortality. A complete list of publications relating to the FORMEN study can be found at https://www.med.kindai.ac.jp/pubheal/FORMEN/Publications.html.

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.

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.

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.

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.

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.

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.

Objective Only a few longitudinal studies have assessed the relationship between bone mineral density (BMD) and arteriosclerosis. This study aimed to determine whether low BMD at baseline is associated with the development of increased arterial stiffness, as evaluated by brachial-ankle pulse wave velocity (baPWV), in Japanese women. Methods A baPWV value of ≥1800 cm/s was adopted as the criterion for increased arterial stiffness, i.e., the outcome of the study. Of the 725 women aged ≥50 years who completed the baseline survey, we excluded the 166 who already met this criterion. Of the remaining women, we analyzed data from the 446 who completed at least one of the follow-up surveys conducted 5 or 10 years after baseline. BMD at the lumbar spine (LS) and total hip (TH) was measured by dual-energy X-ray absorptiometry in the baseline survey. baPWV was measured both at baseline and at follow-up. Multivariate logistic regression was used to evaluate the independent effect of BMD at baseline on developing the outcome during 10-year follow-up. Results We identified 166 women who newly developed increased arterial stiffness. The odds ratios (OR) for a 1 SD decrease in BMD at LS and TH for developing the outcome were 1.20 (95% confidence interval [CI]: 0.91–1.50), and 1.44 (95% CI: 1.14–1.81), respectively, after adjusting for age and systolic blood pressure. After additionally adjusting for baPWV at baseline, the OR for a 1 SD decrease in BMD at TH remained significant (1.33, 95% CI: 1.02–1.72). Conclusion Low BMD at TH was significantly associated with the development of increased arterial stiffness during a 10-year follow-up of Japanese women.

To examine whether or not earlier therapeutic intervention with methotrexate (MTX) prevents the development of rheumatoid arthritis (RA) in patients with recent-onset undifferentiated arthritis (UA) showing high anti-citrullinated peptide antibody (ACPA) titers.The patients were divided into two groups, one was treated with MTX (MTX+ group, n = 29), and the other was treated without MTX (MTX- group, n = 19), and other disease-modifying anti-rheumatic drugs were not permitted in the two groups before the primary endpoint was met. The primary endpoint is the occurrence of definite RA, and it was compared in the two groups after 1 year.The percentage of patients who developed definite RA in the MTX+ group (17.2%) was significantly lower than that in the MTX- group (78.9%) (log-rank test, P0.001, n = 48); adjusted hazards ratio: 0.028 [95% confidence interval (CI): 0.003-0.250, P = 0.001, n = 39]. Treatment effectiveness was not decreased by major risk factors of RA onset such as smoking habits and human leukocyte antigen-DRB1 shared epitope (SE) (smoking habit, odds ratio [OR]: 0.041 [95% CI: 0.007-0.246] P0.001; SE, OR: 0.022 [95% CI: 0.002-0.204] P0.001). The safety issues were comparable between the two groups.This suggests that early therapeutic intervention with MTX could safely prevent the development of RA in patients with recent-onset UA showing high ACPA titers.

FRAX® is widely used to evaluate fracture risk of individuals in clinical settings. However, FRAX® prediction accuracy is not sufficient, and improvement is desired. Trabecular bone score, a bone microarchitecture index, may improve FRAX® prediction accuracy for major osteoporotic fractures in community-dwelling elderly Japanese men. To improve fracture risk assessment in clinical settings, we evaluated whether the combination of FRAX® and Trabecular Bone Score (TBS) improves the prediction accuracy of major osteoporotic fractures (MOFs) in elderly Japanese men compared to FRAX® alone. Two thousand and twelve community-dwelling men aged ≥65 years completed the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Baseline Study comprising lumbar spine (LS) and femoral neck areal bone mineral density (aBMD) measurements, and interviews regarding clinical risk factors required to estimate 10-year risk of MOF (hip, spine, distal forearm, and proximal humerus) using the Japanese version of FRAX® (v.3.8). TBS was calculated for the same vertebrae used for LS-aBMD with TBS iNsight software (v.2.1). MOFs that occurred during the follow-up period were identified by interviews or mail and telephone surveys. Prediction accuracy of a logistic model combining FRAX® score and TBS compared to FRAX® alone was evaluated by area under receiver-operating characteristic curves (AUCs), as well as category-free integrated discrimination improvement (IDI) and net reclassification improvement (NRI). We identified 22 men with MOFs during 8140 person-years (PY) of follow-up among 1872 men; 67 men who suffered from fractures other than MOFs were excluded. Participants with MOFs had significantly lower TBS (p = 0.0015) and higher FRAX® scores (p = 0.0089) than those without. IDI and NRI showed significant improvements in reclassification accuracy using FRAX® plus TBS compared to FRAX® alone (IDI 0.006 (p = 0.0362), NRI 0.452 (p = 0.0351)), although no difference was observed in AUCs between the two. TBS may improve MOF prediction accuracy of FRAX® for community-dwelling elderly Japanese men.

article i nfo End-stage renal failure deteriorates bone mass and increases fracture risk. However, there are conflicting re- ports in the literature regarding the effects of mild to moderate renal dysfunction on bone mineral density (BMD). We investigated the association between renal function and BMD at the spine and hip and bone me- tabolism markers in community-dwelling elderly Japanese men. From 2174 male volunteers aged ≥65 years, we examined 1477 men after excluding those with diseases or medications known to affect bone metabo- lism. Renal function was assessed by serum cystatin C and estimated glomerular filtration rate (eGFR) calcu- lated using the Modification of Diet in Renal Disease Study equation. Bone metabolism was evaluated using levels of serum amino-terminal propeptide of type I procollagen (PINP) and tartrate-resistant acid phospha- tase isoenzyme 5b (TRACP-5b), which represent bone metabolic status independent of renal function. eGFR was inversely associated with BMD after adjusting for potential confounders (P b 0.01). Cystatin C showed a weaker but significant association with BMD. eGFR was modestly positively associated with PINP levels (P = 0.04), although cystatin C concentrations were neither associated with PINP nor TRACP-5b levels. Since BMD integrates bone metabolism from the past to present, inverse associations between renal function and BMD may be attributed to past factors, such as obesity. Our findings suggest that low renal function does not affect bone metabolism in a population of community-dwelling elderly Japanese men. Longitudinal studies will be necessary to clarify whether low renal function affects bone loss.

Frail elderly individuals have elevated risks of both fracture and mortality. We found that incident fractures were associated with an increased risk of death even after adjusting for pre-fracture frailty status as represented by physical performance tests and laboratory tests for common geriatric diseases in community-dwelling elderly Japanese men. While fractures reportedly increase the risk of mortality, frailty may complicate this association, generating a false-positive result. We evaluated this association after adjusting for pre-fracture levels of frailty. We examined 1998 community-dwelling ambulatory men aged ≥65 years at baseline in the Fujiwara-kyo Osteoporosis Risk in Men Study for frailty status as represented by activities of daily living (ADL), physical performance tests (grip strength, one-foot standing balance with eyes open, timed 10-m walk), and laboratory sera tests. Participants were then followed for 5 years for incident clinical fractures and death. Effects of incident fracture on death were determined by Cox proportional hazards model with the first fracture during follow-up as a time-dependent predictor and with frailty status indices as covariates. We identified 111 fractures in 99 men and 138 deaths during the follow-up period (median follow-up, 4.5 years). Participants with incident fractures did not have significantly worse frailty statuses, but did show a significantly higher cumulative mortality rate than those without fractures (p = 0.0047). Age-adjusted hazard ratio (HR) of death for incident fracture was 3.57 (95 % confidence interval: 2.05, 6.24). When adjusted for physical performance, this decreased to 2.77 (1.51, 5.06), but remained significant. The HR showed no significant change when adjusted for laboratory test results (3.96 (2.26, 6.94)). Exclusion of deaths within the first 24 months of follow-up did not alter these results. Incident clinical fracture was associated with an elevated risk of death independently of pre-fracture levels of frailty in community-dwelling elderly men.

Background Trends in the prevalence rates of allergic symptoms in children have been discussed extensively, but it remains uncertain which symptoms increase or decrease over time owing to the lack of large-scale long-term consecutive cross-sectional studies performed on a representative population of children. Objective To clarify the trends in the prevalence rates of allergic symptoms in Japanese children. Methods Total population questionnaire surveys were conducted 15 times from 1975 to 2006 for all children attending public elementary schools in Osaka Prefecture, Japan, with the number of subjects ranging from 460,000 to 900,000. Parents of the children completed the questionnaire about allergic symptoms and other symptoms, including wheeze, physician-diagnosed atopic dermatitis, rhinitis, and itching eyes. Results Response rates were consistently over 90%. The prevalence of wheezing was constant until 1983, then increased from 1983 until 1993, then stabilized at about 4.4%. The lifetime prevalence of atopic dermatitis increased to 24% by 1993, and then decreased. The prevalence of rhinitis increased to 25% by 2003, whereas the prevalence of non-seasonal symptoms plateaued from 1993 on at 11% and vernal symptoms increased. The prevalence of itching eyes continued to increase to 21% in 2006, and vernal symptoms increased sharply. Conclusions In Osaka Prefecture, Japan, the turning point when the prevalence of wheezing in schoolchildren had begun to increase was 1983. And the turning point when the increase in the prevalence of wheezing, atopic dermatitis, and non-seasonal allergic rhinitis turned to decrease or constant was 1993. The prevalence of rhinitis and itching eyes in spring was still increasing in 2006.

Recent animal studies have demonstrated that undercarboxylated osteocalcin upregulates insulin secretion via osteoblast-insulin signaling. However, it remains unclear whether such a pathway exists in humans. This study showed that serum undercarboxylated osteocalcin levels were inversely associated with fasting plasma glucose, hemoglobin A(1c), and homeostasis model assessment of insulin resistance (HOMA-IR) levels in community-dwelling elderly Japanese men.Undercarboxylated osteocalcin (ucOC) was reported to increase insulin secretion and improve glucose tolerance via osteoblast-insulin signaling in animal-based studies. Whether this pathway also exists in humans is unknown. We aimed to clarify whether serum ucOC levels are associated with glycemic status and insulin resistance in the general Japanese population.We included 2,174 Japanese men (≥65 years) who were able to walk without aid from others and lived at home in four cities of Nara Prefecture. We excluded participants with a history of diseases or medications that affect bone metabolism, other than type 2 diabetes mellitus (T2DM). Fasting plasma glucose, glycated hemoglobin A(1c), and HOMA-IR levels were determined as outcome measures.Of the 1,597 participants included in the analysis, both intact OC (iOC) and ucOC levels showed significant inverse correlations with all outcome measures, even after adjusting for potential confounders. Mean values of outcome measures showed a significant decreasing trend with higher quintiles of iOC or ucOC after adjusting for confounders. This trend remained significant for ucOC quintiles after further adjustment for iOC levels, but was not significant for iOC quintiles after adjusting for ucOC levels. These results were attenuated, but still apparent, after excluding participants receiving drug therapy for T2DM.Levels of ucOC, but not iOC, were inversely associated with glycemic index and insulin resistance in a population of Japanese men. These findings will need to be confirmed with longitudinal studies.

A cross-sectional analysis of 1,662 community dwelling elderly Japanese men suggested that habitual natto intake was significantly associated with higher bone mineral density (BMD). When adjustment was made for undercarboxylated osteocalcin levels, this association was insignificant, showing the natto–bone association to be primarily mediated by vitamin K. Low vitamin K intake is associated with an increased risk of hip fracture, but reports have been inconsistent on its effect on BMD. Our first aim was to examine the association between BMD and intake of fermented soybeans, natto, which contain vitamin K1 (20 μg/pack) and K2 (380 μg/pack). Our second aim was to examine the association between undercarboxylated osteocalcin (ucOC), a biomarker of vitamin K intake, and BMD to evaluate the role of vitamin K in this association. Of the Japanese men aged ≥65 years who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men study, 1,662 men without diseases or medications known to affect bone metabolism were examined for associations between self-reported natto intake or serum ucOC levels with lumbar spine or hip BMD. The subjects with greater intake of natto showed significantly lower level of serum ucOC. Analysis after adjustment for confounding variables showed an association of greater intake of natto with both significantly higher BMD and lower risk of low BMD (T-score

Our cross-sectional analysis of 1,576 men aged ≥65 years examined smoking effects on bone status. Number of smoking years was associated with decreased bone mineral density (BMD), after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not affect biochemical marker serum values for bone turnover.The impact of smoking on bone status in men has not been conclusively established. We examined how smoking and its cessation influence bone status and metabolism in men.We analyzed 1,576 men among a baseline survey of Japanese men aged ≥65 years, the Fujiwara-kyo Osteoporosis Risk in Men study, conducted during 2007-2008.Lumbar spine (LS) BMD values among never, former, and current smokers were 1.045 ± 0.194, 1.030 ± 0.189, and 1.001 ± 0.182 g/cm(2) (P = 0.005), respectively, while total hip (TH) BMD values were 0.888 ± 0.120, 0.885 ± 0.127, and 0.870 ± 0.124 (P = 0.078), respectively. The significant trend for LS BMD remained after adjusting for the covariates; age, height, weight, physical activity, milk consumption, and drinking habit (P = 0.036). Among never and ever (current and former) smokers, LS and TH BMD decreased with the number of pack years or the number of smoking years, respectively, adjusted for those covariates. Among ever smokers, LS and TH BMD decreased with the number of smoking years after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not reveal significant effect for serum osteocalcin or tartrate resistant acid phosphatase isoenzyme 5b.The impact of smoking on bone status is mainly associated with the number of smoking years in elderly men.

In Japan, the main source of dioxins is incinerators. This study examined the relationship between the distance of schools from municipal waste incineration plants and the prevalence of allergic disorders and general symptoms in Japanese children. Study subjects were 450,807 elementary school chil- dren aged 6-12 years who attended 996 public ele- mentary schools in Osaka Prefecture in Japan. Parents of school children completed a questionnaire that included items about illnesses and symptoms in the study child. Distance of each of the public ele- mentary schools from all of the 37 municipal waste incineration plants in Osaka Prefecture was measured using geographical information systems packages. Adjustment was made for grade, socioeconomic sta- tus and access to health care per municipality. De- creases in the distance of schools from the nearest municipal waste incineration plant were indepen- dently associated with an increased prevalence of wheeze, headache, stomach ache, and fatigue (adjusted odds ratios (95% confidence intervals) for shortest vs. longest distance categories =1.08 (1.01- 1.15), 1.05 (1.00-1.11), 1.06 (1.01-1.11), and 1.12 (1.08-1.17), respectively). A positive association with fatigue was pronounced in schools within 4 km of the second nearest municipal waste incineration plant. There was no evident relationship between the dis- tance of schools from such a plant and the prevalence of atopic dermatitis or allergic rhinitis. The findings suggest that proximity of schools to municipal waste incineration plants may be associated with an increased prevalence of wheeze, headache, stomach ache, and fatigue in Japanese children.

Summary Background Environmental factors acting early in life are key determinants of the incidence of allergic disease. Whether breastfeeding is protective against allergic disorders remains controversial. Objective The present cross-sectional study examined the relationship between feeding patterns in the first 3 months of life and the prevalence of symptoms of wheeze, atopic eczema, and rhinoconjunctivitis during the past 12 months in Japanese adolescents. Methods The subjects were 5614 of 9008 students (62%) aged 12–15 years from all public junior high schools in Suita, Japan in 2001. This study used the diagnostic criteria of the International Study of Asthma and Allergies in Childhood. Adjustment was made for gender, grade, number of older siblings, and parental history of allergy. Results Feeding pattern was unrelated to the prevalence of wheeze or rhinoconjunctivitis. The prevalence of atopic eczema was significantly higher in children who had been breastfed than in artificial milk feeders (adjusted odds ratios = 1.40 and 1.56, 95% confidence intervals: 1.01–1.98 and 1.13–2.22 for mixed milk intake and breastfeeding only vs. artificial milk consumption, respectively; P = 0.01 for linear trend). When children were divided according to a positive or negative allergic history in at least one parent, an increased prevalence of atopic eczema associated with breastfeeding was found in children with a negative parental allergic history compared with those with a positive parental allergic history. Conclusion The findings suggest that breastfeeding may be associated with an increased prevalence of atopic eczema, especially among children without a parental history of allergy.

Trends in the prevalence rates of allergic symptoms in children have been discussed extensively, but it remains uncertain which symptoms increase or decrease over time owing to the lack of large-scale long-term consecutive cross-sectional studies performed on a representative population of children.To clarify the trends in the prevalence rates of allergic symptoms in Japanese children.Total population questionnaire surveys were conducted 15 times from 1975 to 2006 for all children attending public elementary schools in Osaka Prefecture, Japan, with the number of subjects ranging from 460,000 to 900,000. Parents of the children completed the questionnaire about allergic symptoms and other symptoms, including wheeze, physician-diagnosed atopic dermatitis, rhinitis, and itching eyes.Response rates were consistently over 90%. The prevalence of wheezing was constant until 1983, then increased from 1983 until 1993, then stabilized at about 4.4%. The lifetime prevalence of atopic dermatitis increased to 24% by 1993, and then decreased. The prevalence of rhinitis increased to 25% by 2003, whereas the prevalence of non-seasonal symptoms plateaued from 1993 on at 11% and vernal symptoms increased. The prevalence of itching eyes continued to increase to 21% in 2006, and vernal symptoms increased sharply.In Osaka Prefecture, Japan, the turning point when the prevalence of wheezing in schoolchildren had begun to increase was 1983. And the turning point when the increase in the prevalence of wheezing, atopic dermatitis, and non-seasonal allergic rhinitis turned to decrease or constant was 1993. The prevalence of rhinitis and itching eyes in spring was still increasing in 2006.

There are no data concerning a relationship between alcohol and bone status from a large-scale community-based study of elderly Japanese men. The baseline survey for the Fujiwara-kyo Osteoporosis Risk in Men Study was performed in 2174 male participants during the period from 2007 to 2008 in Nara Prefecture, Japan. Among them 1665 fitted the following inclusion criteria: (a) age ≥65years, (b) no diseases or drug therapy that could affect bone mineral density (BMD). We analyzed 1421 men with complete information about alcohol intake. We found that alcohol intake and BMD were positively correlated after adjustment for age, body mass index, natto intake, milk intake, smoking, physical activity, education, marital status, and hypertension. Adjusted total hip BMD of men with alcohol intake >39g/day was 0.90g/cm(2) and that of abstainers was 0.85g/cm(2). With regard to bone turnover markers, alcohol intake was inversely associated with serum levels of osteocalcin and tartrate-resistant acid phosphatase isoenzyme 5b. A two-piece linear regression model revealed a positive relationship between alcohol intake and crude mean BMD for the total hip in those with alcohol intake of less than 55g/day. In contrast, alcohol intake and BMD in those with an alcohol intake of 55g/day or more was inversely correlated. The present large-scale study of elderly Japanese men revealed that although an alcohol intake of

IOL術後の矯正のために眼鏡が必要であるが,一度処方した後の状態や再処方については関心が薄くなりがちである.そこで,眼内レンズ術後の眼鏡処方について検討した.対象は1988年1月より1990年4月まで眼内レンズ移植手術をおこなった195例251眼で,患者の術眼の印象を知るためにアンケート調査をおこなった.眼鏡を処方された症例は63例77眼(31%)で,処方されなかった症例は132例174眼(69%)であった.眼鏡処方された症例は,術後5ヶ月までに,裸眼視力が0.5未満(90%)で屈折力が+1Dから-2Dの範囲にあり(78%),倒乱視のある(49%)比較的年齢の若い老人に多くみられ,幾分男性の割合が高かった.眼鏡処方しなかった症例のうち,アンケート調査で『よく見える』と回答した症例の84%は裸眼視力が0.15以上で,屈折力は±2D以下であった.眼鏡を再処方した人は4例7眼で,眼鏡を処方した人の66%が常時使用していた.

To elucidate the actual status of indoor air pollution at newly built or renovated elementary schools, and to evaluate its effects on health symptoms in the affected children.In the classrooms of four newly built or renovated elementary schools in Osaka Prefecture, indoor air levels of formaldehyde and volatile organic compounds (VOC) were measured immediately, 1 month, 3 months, 10 months and 22 months after the completion of the construction work. Also, questionnaire surveys regarding subjective symptoms of sick building syndrome were conducted before and after the renovation on the children who attended classes in the renovated rooms.In the newly built computer classroom, more formaldehyde was detected one month after the completion of the construction work, when computers and furniture were carried in, than immediately after the completion of the work. Then, during the summer season, even 10 months and 22 months after completion of the new building, formaldehyde above the guideline values was detected. In the renovated common classrooms, the formaldehyde level was the same as that in the classrooms which did not undergo renovation, but VOC levels were higher immediately after the completion of the construction work, and the toluene level was above the guideline value. In 4-story reinforced concrete school buildings, indoor air pollution tended to be higher on the third and the fourth floors than on the first and the second floors. In 3-story school buildings, indoor air pollution tended to be higher on the third floor than on the second floor. The survey of subjective symptoms of the children revealed a tendency toward an increase in the prevalence of sick building syndrome after a renovation. However, the actual number of the children complaining of the symptoms hardly changed. Instead, the number of symptoms for each subject increased, and this increase was significant in 5th and 6th grade boys.In the some classrooms of newly built or renovated elementary schools, chemical substances above the guideline values may be detected. In such classrooms, more ventilation is required.

An investigation was conducted on the influence of genetic and lifestyle factors related to the determination of eating behavior of human beings. The objective was to obtain information about lifestyle factors that may help health professionals intervene in terms of the prevention of diet-related diseases.The subjects were 180 pairs of adult twins aged over thirty, comprising of 134 monozygotic (MZ) and 46 dizygotic (DZ) pairs. Every subject was given an interview concerning dietary habits, food preference, food intake, as a part of medical examination. The intake of food containing salt and fat, the intake of food meals, the frequency of daily meals, and the frequency of eating 18 sorts of food were assessed on an individual basis, with a questionnaire on nutrition. The expected and observed values of intrapair concordance rates were calculated, and compared within each zygosity, using the chi-square test.Significant differences between the expected and observed for intrapair concordance rates were shown with monozygotic twins, regarding every category of question. Comparing MZ pairs who had lived apart before their twenties with the other MZ pairs, the latter had a tendency to show significant differences between the expected and observed values of intrapair concordance rate, regarding every category of question. In each case, the observed values were higher than the expected values.The study implied that both genetic and lifestyle factors influence the determinants of eating behavior of human beings. This finding shows the importance of understanding individual characteristics of food preference and eating behavior for intervention regarding lifestyle factors for prevention of diet-related diseases.

A relationship between distance from major roads and the prevalence of allergic disorders and general symptoms among junior high school students was assessed, separating the effects of distance of residence and school from the roads. Study subjects were 5,652 students aged 12 to 15 years. This study used diagnostic criteria from the International Study of Asthma and Allergies in Childhood. The questionnaire also asked about symptoms of headache, stomachache, tiredness, and cough and the shortest distance from residence to major roads. Distance from school to the nearest major road was measured on a map. Adjustment was made for gender, grade, the number of older siblings, smoking in the household, and maternal history of allergy. A shorter distance between residence and major roads was associated with an increased prevalence of headache, stomachache, tiredness, and cough. There was a marginally significant positive association between residence facing major roads and the prevalence of allergic rhinoconjunctivitis. Residence within 100 m of major roads showed a tendency for a positive relationship with the prevalence of wheeze and atopic dermatitis. There was no apparent relationship between distance of school from major roads and allergic disorders or the general symptoms. The findings suggest that proximity of residence, not school, to major roads may be associated with an increased prevalence of allergic disorders, headache, stomachache, and tiredness among Japanese adolescents. Further investigations with more precise and detailed exposure and health outcome measurements are needed to corroborate the relationship between traffic related factors and allergic disorders and general symptoms.