Neurolymphomatosis diagnosed after a recurrence of facial palsy.

Neurolymphomatosis (NL) is a rare complication of non-Hodgkin's lymphoma, characterized by the infiltration of lymphoma cells into the peripheral nerves. A 54-year-old woman initially presented with right facial palsy without any other significant symptoms and was diagnosed with Bell's palsy. Despite initial improvement, her condition recurred, prompting further evaluation. Magnetic resonance imaging (MRI) revealed contrast enhancement from the tympanic segment to the surface of the masseter muscle along the right facial nerve and an adjacent mass lesion. Biopsy of the mass revealed a diagnosis of T-cell/histiocyte-rich large B-cell lymphoma. Chemotherapy resulted in complete resolution of facial palsy. Follow-up MRI confirmed the absence of contrast enhancement along the facial nerve. Facial palsy was considered to be caused by NL. This case was classified as that of primary NL because the facial palsy was the first manifestation of a hematologic malignancy. Recurrent facial palsy, which is atypical in Bell's palsy, led to further evaluation with MRI, which finally resulted in the diagnosis of malignant lymphoma. In cases of recurrent facial palsy, clinicians should consider various diagnoses, including that of NL, and advocate early imaging tests and biopsy, if possible, for accurate diagnosis and improved outcomes.

Association between the 110-kDa C-terminal agrin fragment and skeletal muscle decline among community-dwelling older women.

BACKGROUND: C-terminal agrin fragment (CAF) is a biomarker for neuromuscular junction degradation. This study aimed to investigate whether 110-kDa CAF (CAF110) was associated with the presence and incidence of low muscle mass and strength. METHODS: This cross-sectional retrospective cohort study comprised women aged ≥65 years. We measured muscle mass using a dual-energy X-ray absorptiometry scanner, hand-grip strength, and blood sampling between 2011 and 2012. A follow-up study with the same measurements was conducted between 2015 and 2017. Low muscle mass and strength were defined as an appendicular skeletal muscle mass index <5.4 kg/m2 and hand-grip strength <18 kg, respectively. The CAF110 level was measured using enzyme-linked immunosorbent assay kits. RESULTS: In total, 515 women (74.3 ± 6.3 years) were included in this cross-sectional analysis. Of these, 101 (19.6%) and 128 (24.9%) women presented with low muscle mass and strength, respectively. For low muscle mass, the odds ratios (ORs) of the middle and highest CAF110 tertile groups, compared with the lowest group, were 1.93 (95% confidence interval: 1.09-3.43; P = 0.024) and 2.15 (1.22-3.80; P = 0.008), respectively. After adjusting for age, the ORs remained significant: 1.98 (1.11-3.52; P = 0.020) and 2.27 (1.28-4.03; P = 0.005), respectively. Low muscle strength ORs of all the CAF110 tertile groups were not significant. In the longitudinal analysis, 292 and 289 women were assessed for incidents of low muscle mass and strength, respectively. Of those, 34 (11.6%) and 20 (6.9%) women exhibited low muscle mass and strength, respectively. For incident low muscle mass, the crude OR of the CAF110 ≥ the median value group was marginally higher than that of the CAF110 < median value group (median [interquartile range]: 1.98 [0.94-4.17] (P = 0.072). After adjusting for age and baseline muscle mass, the OR was 2.22 [0.97-5.06] (P = 0.058). All low muscle strength ORs of the median categories of CAF110 were not significant. CONCLUSIONS: CAF110 was not associated with low muscle strength. However, CAF110 may be a potential marker for the incidence of low muscle mass.

Risk factors for future osteoporosis in perimenopausal Japanese women.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Combined results of three physical performance tests predict incident fracture independently of aBMD in community-dwelling elderly Japanese men: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

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.

Determinants of bone health in elderly Japanese men: study design and key findings of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study.

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 .

Relationships between serum uric acid concentrations, uric acid lowering medications, and vertebral fracture in community-dwelling elderly Japanese men: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

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.

Natto Intake is Inversely Associated with Osteoporotic Fracture Risk in Postmenopausal Japanese Women.

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 < 1 pack (approximately 40 g)/wk natto intake were 0.72 (95% CI: 0.52, 0.98) and 0.51 (95% CI: 0.30, 0.87) for 1-6 and ≥7 packs/wk, respectively. After further adjustment for BMI, history of osteoporotic fractures, history of myocardial infarction or stroke, diabetes mellitus, current smoking, alcohol intake, frequency of tofu and other soybean product intakes, and dietary calcium intake, the HRs were 0.79 (95% CI: 0.56, 1.10) and 0.56 (95% CI: 0.32, 0.99) for 1-6 and ≥7 packs/wk, respectively. Frequency of tofu or other soybean product intakes had no association with the risk of osteoporotic fractures. CONCLUSIONS: Habitual natto intake may be associated with a reduced risk of osteoporotic fractures independent of confounding factors, including BMD, in Japanese postmenopausal women. This trial was registered at umin.ac.jp as UMIN 000032869.

Decreased bone mineral density and osteoporotic fractures are associated with the development of echogenic plaques in the carotid arteries over a 10-year follow-up period: The Japanese Population-based Osteoporosis (JPOS) Cohort Study.

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.

Association between hand-grip strength and site-specific risks of major osteoporotic fracture: Results from the Japanese Population-based Osteoporosis Cohort Study.

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.

Increased risk of osteoporotic fracture in community-dwelling elderly men 20 or more years after gastrectomy: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

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.

Hyperglycemic status is associated with an elevated risk of osteoporotic fracture in community-dwelling elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) cohort study.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Does Trabecular Bone Score (TBS) improve the predictive ability of FRAX® for major osteoporotic fractures according to the Japanese Population-Based Osteoporosis (JPOS) cohort study?

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.

Muscle strength is associated with bone health independently of muscle mass in postmenopausal women: the Japanese population-based osteoporosis study.

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 < 0.05) positive relationships with aBMDs at several skeletal sites after adjusting for ASMI and age (standardized partial regression coefficient (ß) = 0.102 at femoral neck, ß = 0.126 at lumbar spine). Adjusted means of aBMD at the femoral neck and lumbar spine showed significant increasing trends from the lowest to highest tertile of grip strength. Our findings indicate that muscle strength is associated with aBMD at several sites independently of muscle mass in Japanese postmenopausal women. Thus, postmenopausal women with strong muscle strength tend to have a healthy bone status regardless of muscle size.

Crohn's disease-specific mortality: a 30-year cohort study at a tertiary referral center in Japan.

BACKGROUND: In this study, survival and cause of death were investigated in patients with Crohn's disease (CD) at a tertiary referral center. METHODS: A database was created based on the medical records of 1108 CD patients who had a history of visiting our hospital to investigate background characteristics, cumulative survival rates from diagnosis, causes of death, and the standardized mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey of patients followed up inadequately was also conducted. The cumulative survival rate from diagnosis was determined using the life table method and compared with that of a sex- and age-matched population model from the year 2000. RESULTS: The study included 1108 patients whose mean age at diagnosis was 25.6 ± 10.8 years. The mean duration of follow-up was 14.6 ± 9.4 years, and there were 52 deaths. The cumulative survival rate was significantly lower 25 years after the diagnosis of CD (91.7%) than in the standard population model (95.7%). SMRs for both all causes [3.5; 95% confidence interval (CI): 2.7-4.6] and CD-specific causes (36.7; 95% CI 26.1-51.6) were high. Among the CD-specific causes, SMRs were especially high for small intestine and colorectal cancers, gastrointestinal diseases including intestinal failure (IF), perioperative complications, and amyloidosis. CONCLUSION: The SMRs for both all causes and CD-specific causes were high in CD patients. CD-specific causes including intestinal cancer, IF, perioperative complications, and amyloidosis showed especially high SMRs.

Low bone mineral density is associated with an elevated risk of developing increased arterial stiffness: A 10-year follow-up of Japanese women from the Japanese Population-based Osteoporosis (JPOS) cohort study.

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.

Comparison of Small Bowel Lesions Using Capsule Endoscopy in Ulcerative Colitis and Crohn's Disease: A Single-Center Retrospective Analysis.

BACKGROUND: Capsule endoscopy (CE) has allowed the characterization of small bowel lesions. However, small bowel lesions in ulcerative colitis (UC) have not been elucidated and no studies have compared between UC and Crohn's disease (CD). AIM: The objective of this study was to investigate the small bowel lesions in UC, and to characterize UC lesions by comparison with CD. METHODS: Subjects comprised 54 UC patients and 39 CD patients who underwent CE. We retrospectively investigated characteristics of small bowel lesions in UC. We also compared endoscopic findings and degree of inflammation between UC and CD. RESULTS: The incidence of small bowel lesions in UC was 27.8%. The group with small bowel lesions exhibited higher endoscopic activity in the colon than without small bowel lesions (p = 0.002). Comparing small bowel lesions between UC and CD, significantly more ulcerative lesions, notched appearance, longitudinal tendency of lesions, and cobblestone appearance were seen in CD. The Lewis score was significantly higher in CD than UC in the second and third tertiles (205 ± 379 vs. 73 ± 223, p = 0.01; 358 ± 449 vs. 105 ± 333, p < 0.001). CONCLUSIONS: Small bowel lesions in UC were linked to colonic activity. UC and CD differ in terms of the morphology and distribution of small bowel lesions.

Ratio of Endogenous Secretory Receptor for Advanced Glycation End Products to Pentosidine Predicts Fractures in Men.

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.

S-Adenosylmethionine Synthesis Is Regulated by Selective N6-Adenosine Methylation and mRNA Degradation Involving METTL16 and YTHDC1.

S-adenosylmethionine (SAM) is an important metabolite as a methyl-group donor in DNA and histone methylation, tuning regulation of gene expression. Appropriate intracellular SAM levels must be maintained, because methyltransferase reaction rates can be limited by SAM availability. In response to SAM depletion, MAT2A, which encodes a ubiquitous mammalian methionine adenosyltransferase isozyme, was upregulated through mRNA stabilization. SAM-depletion reduced N6-methyladenosine (m6A) in the 3' UTR of MAT2A. In vitro reactions using recombinant METTL16 revealed multiple, conserved methylation targets in the 3' UTR. Knockdown of METTL16 and the m6A reader YTHDC1 abolished SAM-responsive regulation of MAT2A. Mutations of the target adenine sites of METTL16 within the 3' UTR revealed that these m6As were redundantly required for regulation. MAT2A mRNA methylation by METTL16 is read by YTHDC1, and we suggest that this allows cells to monitor and maintain intracellular SAM levels.