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 .

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.

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.

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.

Long-term course of Crohn's disease in Japan: Incidence of complications, cumulative rate of initial surgery, and risk factors at diagnosis for initial surgery.

BACKGROUND AND AIMS: Intestinal complications of stenosis or fistula may occur during the course of Crohn's disease (CD), and surgery is performed in a fair number of patients. The risk factors for initial surgery in a Japanese hospital-based cohort of CD patients were evaluated. METHODS: This study was a single-center, retrospective, cohort study. The subjects were 520 patients who underwent inpatient and outpatient treatment at our hospital, had a definitive diagnosis of CD, and no previous surgery. Three parameters were investigated: (i) cumulative incidence of stenosis and fistula; (ii) cumulative rate of initial surgery for each disease type; and (iii) risk factors at diagnosis for initial surgery. RESULTS: (i) Stenosis and fistula increased with time, with stenosis or fistula appearing in about half of the patients after 5 years. (ii) The cumulative rate of initial surgery was about 50% after 10 years. (iii) The patient factors at diagnosis of current smoker, upper gastrointestinal disease, stricturing, penetrating, moderate to severe stenosis of the jejunum, moderate to severe stenosis of the ileum, and moderate to severe stenosis of the terminal ileum were risk factors for initial surgery. CONCLUSIONS: Stenosis or fistula appeared in about half of the patients after 5 years from diagnosis. When upper gastrointestinal disease or complicated small intestinal lesions are seen at the time of diagnosis, the cumulative rate of initial surgery is significantly higher.

Mucosal healing of ileal lesions is associated with long-term clinical remission after infliximab maintenance treatment in patients with Crohn's disease.

BACKGROUND AND AIM: The aim of the present study was to endoscopically evaluate ileal mucosal healing during maintenance therapy with infliximab in order to investigate the clinical significance of endoscopic examination of ileal lesions in Crohn's disease patients. METHODS: This study retrospectively analyzed 54 patients who mainly had active ulcers of the ileum on endoscopy at baseline who were responsive to infliximab induction and who received infliximab maintenance therapy. Mucosal healing was defined as no ulcer or only ulcer scar. At the time of follow-up endoscopy after starting infliximab, endoscopic score, mucosal healing, and clinical remission were evaluated. On long-term follow up, correlations between mucosal healing and long-term clinical remission, and between mucosal healing and the need for major abdominal surgery, were also evaluated. RESULTS: Ileal mucosal healing and complete mucosal healing were significantly correlated with clinical remission (P = 0.046, P = 0.0001, respectively). The rate of long-term clinical remission was significantly higher in patients with complete mucosal healing (P = 0.025). The rate of major abdominal surgery for strictures was significantly lower in patients with complete mucosal healing (P = 0.044). CONCLUSIONS: Complete mucosal healing after 1-2 years was a predictive factor for long-term clinical remission up to 4 years after starting infliximab. A lack of complete mucosal healing was a predictive factor for major abdominal surgery for strictures. The present study suggests that endoscopic evaluation of ileal lesions is useful for long-term prognosis of Crohn's disease patients.

Second peak in the distribution of age at onset of ulcerative colitis in relation to smoking cessation.

BACKGROUND AND AIM: The prevalence of ulcerative colitis (UC) is increasing steadily in Japan. In Western countries, a bimodal distribution, with UC onset peaks in youth and middle age, is observed, and smoking cessation is reported as a risk factor for UC. However, there are few reports on a bimodal distribution of onset age among Japanese patients. Therefore, the distribution of onset age and factors related to late onset (i.e. onset at 50 years old or later) were investigated in UC patients in Japan. METHODS: A questionnaire survey of UC patients was conducted to investigate the distribution of the age of onset and factors that may be related to UC onset in a Japanese university hospital. RESULTS: Among 465 UC patients, 343 patients responded. In the distribution of onset age, a large peak was seen in patients aged 10-20s, and small peaks were seen at age 40-44 years and then in 50-60s. In addition, the onset age was older in the UC patients diagnosed in 2001 or later than in those diagnosed in 2000 or earlier. Late onset was more common among the UC patients diagnosed in 2001 or later (vs 2000 or earlier: interaction odds ratio = 4.98, 95% CI: 2.21-11.25, P < 0.01) and among former smokers (vs never-smokers: interaction odds ratio = 2.93, 95% CI: 1.40-6.14, P < 0.01) on multivariate analysis. CONCLUSIONS: Similar to UC patients in Western countries, a bimodal distribution of onset age was also observed in Japanese UC patients, and smoking cessation may partly contribute to the increase in late-onset UC patients in recent years in Japan.

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.

Cancer risk in Japanese Crohn's disease patients: investigation of the standardized incidence ratio.

BACKGROUND AND AIM: There have been very few reported investigations on the standardized incidence ratio (SIR) of intestinal cancer and all cancers other than intestinal cancer with Crohn's disease (CD) by organ in Japan. This study examined the risk of developing cancer (i.e. SIR) that occurs in association with CD. METHODS: The subjects were 770 CD patients managed at our hospital department, which specializes in inflammatory bowel disease, during the approximately 25 years from July 1985 to August 2010. The number of expected cancer patients in a healthy population matched for sex and age with the CD patients in our hospital was then calculated. The relative risk, or SIR, was also calculated. RESULTS: The total observation period was 10,552 person-years, during which 19 cases (2.5%) of cancer were discovered in 770 subjects. The cancer cases included nine cases of colorectal cancer (CRC), one case of small bowel cancer, one case of stomach cancer, three cases of acute myeloid leukemia, two cases of endometrial cancer, one case of lung cancer, one case of skin cancer, and one case of thyroid cancer. The SIR for cancers in Japan in 2003 was 0.87 (95% confidence interval [CI] 0.52-1.35) for all cancers, 2.79 (95% CI 1.28-5.29) for CRC, and 6.94 (95% CI 1.43-20.3) for leukemia. CONCLUSIONS: Among the cancers in CD patients in our hospital, no significant difference was seen in the risk for all cancers in comparison with the standard population. However, the risks for CRC and leukemia were significantly higher than in the standard population.

Incidence, clinical characteristics, long-term course, and comparison of progressive and nonprogressive cases of aphthous-type Crohn's disease: a single-center cohort study.

BACKGROUND/AIMS: In Japan, aphthous-type Crohn's disease (type A CD) is thought to represent an early phase of Crohn's disease (CD), and diagnosis of type A CD is possible in the diagnostic criteria for CD in Japan. However, the details of type A CD are not well understood. METHODS: Subjects comprised 649 CD patients diagnosed between 1985 and 2011. The incidence of type A CD over time was clarified in two periods (1985-2004 and 2005-2011). The course of type A CD was also investigated, and cases that did and did not progress to typical CD were compared. RESULTS: No significant difference was seen in the incidence of type A CD between the two periods (5.2 vs. 8.5%, p = 0.125). Type A CD patients followed at our hospital progressed to typical CD at a rate of 59.3%. In comparing progressive and nonprogressive cases, the frequency of large, densely distributed aphthous lesions in the small intestine was higher among progressive cases (p = 0.018). CONCLUSION: Type A CD is an early phase of CD, and CD diagnostic criteria including early cases are valid in Japan.

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.

Effectiveness of magnesium citrate as preparation for capsule endoscopy: a randomized, prospective, open-label, inter-group trial.

BACKGROUND AND AIM: Capsule endoscopy (CE) is effective in the detection of small bowel lesions. Many studies have been conducted on the effectiveness of preparations in improving diagnostic yield, but an effective method has yet to be confirmed. We used magnesium citrate as preparation for CE and evaluated its effectiveness. METHODS: 50 patients who underwent CE were randomly allocated to two groups - group A (preparation provided) and group B (no preparation). Group A were administered 34 g of magnesium citrate at 8 p.m. the night before the examination. Group B were not administered a laxative. RESULTS: The cleansing efficacy score was 24.4 ± 4.4 points for group A and 22.9 ± 4.4 points for group B, with no significant difference between groups. No significant difference was seen in the large bowel arrival rate between groups: 14 cases (63.6%) for group A and 16 cases (72.7%) for group B. CONCLUSION: In this study, superiority was not seen for cleansing efficacy, large bowel arrival rate for the preparation method involving administration of hypertonic MC solution 12 h prior to the procedure.

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.

Small bowel lesions detected with wireless capsule endoscopy in patients with active ulcerative colitis and with post-proctocolectomy.

BACKGROUND: Although rare, duodenal lesions have been reported in association with ulcerative colitis (UC); however, there have been very few reports on small bowel lesions, and many aspects of their pathology and frequency remain unknown. This study determined whether small bowel lesions are present in UC by using wireless capsule endoscopy (WCE). PATIENTS AND METHODS: WCE was performed on 20 patients with active UC and 10 who had undergone proctocolectomy. RESULTS: Small bowel lesions (e.g. edema or ulcers) were observed in 11 of the 30 patients (36.6%): in eight (40%) of the 20 patients with active UC and in three (33.3%) of the 10 post-proctocolectomy patients. Ulcers that extended over a long segment or whole tertile of the small bowel were observed in five patients, and the disease type was extensive colitis in three of these and pouchitis in the other two. Age at onset was significantly lower in the 20 active UC patients that had small bowel lesions. CONCLUSION: WCE revealed the presence of ulcers that extended over a long segment or a whole tertile in the small bowel in active extensive colitis and pouchitis. In future, it will be necessary to assess the clinical significance of small bowel lesions in UC in detail.

Smoking among premenopausal women is associated with increased risk of low bone status: the JPOS Study.

The impact of smoking on peak bone density has not been conclusively established. We examined how smoking exposure influences bone mineral density (BMD) or the risk of low bone status in premenopausal women. We conducted a baseline survey with a representative sample of Japanese women in 1996. The effect of current and former smokers (ever-smoker) was investigated with 789 premenopausal women aged 20-40 years. The multiple regression with stepwise method was used to identify significant determinants for BMD or the risk of low bone status (T-score < -1) with age, height, weight, calcium intake, coffee consumption, exercise habits, level of daily activity, parity >or= 1, and smoking as explanatory variables. The smoking effect was determined after adjusting for age, height, weight, and significant variables in the multiple regression with stepwise method. Ever-smoker was significantly associated with decreased lumbar BMD adjusted for age, height, and weight. The odds ratio of an ever-smoker for low bone status at the lumbar spine was 2.03 (95% CI 1.12, 5.82) adjusted for age, height, weight, and parity. The odds ratio for low bone status at the lumbar spine was 1.59 (95% CI 0.65, 3.91) and 2.55 (95% CI 1.12, 5.82) in those with less than 3 pack-years of tobacco use and in those with 3 or more pack-years of tobacco use, respectively. These values were adjusted for age, height, weight, and parity using a never-smoker as a reference. Cumulative smoking exposure may be associated with increased risk of low bone status among premenopausal women.

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.

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.