Relative Importance of Central and Peripheral Adiposities on Cardiometabolic Variables in Females: A Japanese Population-Based Study.

In epidemiological studies, there is little evidence regarding the relative impact of central adiposity and peripheral adiposity on cardiometabolic risk factors, especially in Asian populations. This study investigated associations between central-to-peripheral fat ratios and cardiometabolic variables using data from a population-based study of Japanese women. The source population was composed of 1800 women aged 50 yr or older at the 15th- to 16th-yr follow-up survey of the Japanese Population-Based Osteoporosis Cohort Study. This study analyzed cross-sectional data from 998 women for whom complete information about body fat variables according to dual-energy X-ray absorptiometry, cardiometabolic variables, and potential confounding factors was available. Both before and after adjusting for potential confounding factors, trunk-to-appendicular fat ratios showed significant (p < 0.05) correlations with brachial-ankle pulse wave velocity, serum lipids, and hemoglobin A1c levels. Relationships between fat ratios and cardiometabolic variables were independent of relationships between fat volumes (in whole body or in trunk) and cardiometabolic variables. Furthermore, relationships between trunk-to-appendicular fat ratios and cardiometabolic variables were observed among women in the lowest tertile of total body fat (brachial-ankle pulse wave velocity, ß = 0.08; high-density lipoprotein cholesterol, ß = -0.32; low-density lipoprotein cholesterol, ß = 0.15; and hemoglobin A1C, ß = 0.16; p < 0.05, respectively). Central adiposity is more related to cardiometabolic variables than peripheral adiposity. Information on central-to-peripheral fat ratios is particularly valuable for the evaluation of relatively thin Japanese women.

Tracking of appendicular bone mineral density for 6 years including the pubertal growth spurt: Japanese Population-based Osteoporosis kids cohort study.

Bone development up to early adulthood plays an important role in determining the risk of osteoporosis later in life. However, bone development in children has not been fully documented by longitudinal studies in Japanese children. The purpose of this study is to determine the degree of tracking of areal bone mineral density (aBMD) from pre-puberty to 6-year follow-up, and to determine the target period to achieve maximal peak aBMD. This study was conducted as the pediatric part of a larger cohort study, the Japanese Population-based Osteoporosis (JPOS) study. Of 448 children aged 9-12 years who completed the baseline survey, 225 participated in the follow-up study 6 years later (follow-up rate: 50.2%). aBMD at the forearm was measured using dual-energy X-ray absorptiometry. aBMD values in pre-pubertal children at baseline showed a significant tracking correlation with aBMD obtained at 6-year follow-up in both genders (boys r = 0.655, girls r = 0.759). Although boys and girls in the lowest quartile of aBMD pre-pubertally had greater annual increases in aBMD from pre-puberty to 6-year follow-up than those in other aBMD quartiles, they still showed the lowest mean aBMD at 6-year follow-up. Children with lower pre-pubertal aBMD showed greater increases in BMD up until 6-year follow-up, but the increase was not great enough to catch up with other children. About 50% of the variance in aBMD at 6-year follow-up was determined by the aBMD achieved during the pre-pubertal period. Activities that increase aBMD are important not only for children during puberty, but also for younger pre-pubertal children.

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.

Cohort Profile: The Japanese Population-based Osteoporosis (JPOS) Cohort Study.

The Japanese Population-based Osteoporosis (JPOS) Cohort Study was launched in 1996 to produce a reference database of areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA) and bone turnover markers in the Japanese female population and to determine risk factors for osteoporotic fractures. At baseline, 3984 women aged 15 to 79 years were randomly selected to provide representative bone status data and aBMD values for the diagnosis of osteoporosis. Follow-up surveys were conducted in 1999, 2002, 2006 and 2011/12 to determine changes in aBMD and identify incident morphometry-confirmed vertebral fractures and clinical fractures. These outcomes were obtained from 2174 women who participated in at least one follow-up survey. JPOS is a unique resource of individual-level bone health information with radiological and biological archives that include DXA images, and serum, plasma and DNA for future analyses with emerging radiological and biological techniques. The JPOS dataset is not freely available, but new collaborations are encouraged. Potential collaborators are invited to contact the Secretary General (M.I.) at the administrative office of the JPOS Study Group.

Prediction of bone mineral density from vitamin D receptor polymorphisms is uncertain in representative samples of Japanese Women. The Japanese Population-based Osteoporosis (JPOS) Study.

BACKGROUND: Vitamin D receptor (VDR) gene polymorphisms have been inconsistently associated with bone mineral density (BMD). To precisely evaluate the associations between three VDR gene polymorphisms and BMD, we performed a large-scale representative study of the Japanese female population. METHODS: Fifty women were randomly selected from each of the 5-year age stratified populations (15-79 years) in each of the three municipalities examined, as a part of the Japanese population-based osteoporosis (JPOS) baseline study in 1996. In the study, BMD at the lumbar spine, hip, and distal forearm were measured using dual energy X-ray absorptiometry (DXA). Two polymorphisms were determined in the VDR gene locus identified by the restriction endonucleases ApaI and TaqI through a novel allele discrimination method using two different allele-specific fluorescence probes. The other VDR gene polymorphism was identified by the restriction endonuclease FokI using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Changes in BMD were determined in a follow-up study 3 years after the baseline study. RESULTS: After the exclusion of women who had any medical or menstrual history affecting BMD, 1434 women were analysed. The annual per cent changes in BMD at the lumbar spine over 3 years in subjects with tt genotype in the TaqI polymorphism were different from other genotypes, both in the women who were premenopausal at the follow-up survey (F-premenopausal women) and in the women who were postmenopausal at the baseline survey (B-postmenopausal women). However, the effects of tt genotype on change in BMD were opposite in the two groups. In addition, these associations or tendencies were not observed at the different skeletal sites. CONCLUSIONS: This study revealed that none of the individual VDR gene polymorphisms displayed consistent association with baseline BMD or BMD change. Therefore, the effect of the VDR genotype on bone mass is negligible in Japanese women.

Trabecular bone score (TBS) predicts vertebral fractures in Japanese women over 10 years independently of bone density and prevalent vertebral deformity: the Japanese Population-Based Osteoporosis (JPOS) cohort study.

Bone strength is predominantly determined by bone density, but bone microarchitecture also plays an important role. We examined whether trabecular bone score (TBS) predicts the risk of vertebral fractures in a Japanese female cohort. Of 1950 randomly selected women aged 15 to 79 years, we analyzed data from 665 women aged 50 years and older, who completed the baseline study and at least one follow-up survey over 10 years, and who had no conditions affecting bone metabolism. Each survey included spinal imaging by dual-energy X-ray absorptiometry (DXA) for vertebral fracture assessment and spine areal bone mineral density (aBMD) measurement. TBS was obtained from spine DXA scans archived in the baseline study. Incident vertebral fracture was determined when vertebral height was reduced by 20% or more and satisfied McCloskey-Kanis criteria or Genant's grade 2 fracture at follow-up. Among eligible women (mean age 64.1 ± 8.1 years), 92 suffered incident vertebral fractures (16.7/10(3) person-years). These women were older with lower aBMD and TBS values relative to those without fractures. The unadjusted odds ratio of vertebral fractures for one standard deviation decrease in TBS was 1.98 (95% confidence interval [CI] 1.56, 2.51) and remained significant (1.64, 95% CI 1.25, 2.15) after adjusting for aBMD. The area under the receiver operating characteristic curve of TBS and aBMD combined was 0.700 for vertebral fracture prediction and was not significantly greater than that of aBMD alone (0.673). However, reclassification improvement measures indicated that TBS and aBMD combined significantly improved risk prediction accuracy compared with aBMD alone. Further inclusion of age and prevalent vertebral deformity in the model improved vertebral fracture prediction, and TBS remained significant in the model. Thus, lower TBS was associated with higher risk of vertebral fracture over 10 years independently of aBMD and clinical risk factors including prevalent vertebral deformity. TBS could effectively improve fracture risk assessment in clinical settings.

Arm span increases predictive value of models for prevalent vertebral deformities: the Japanese Population-based Osteoporosis (JPOS) Study.

OBJECTIVE: We examined anthropometric indicators to improve predictive ability of asymptomatic vertebral fracture screening models. STUDY DESIGN AND SETTING: Data were obtained from the 1996 Japanese Population-based Osteoporosis (JPOS) Study. McCloskey-Kanis criteria diagnosed vertebral deformities on X-ray absorptiometric images in 693 women aged > or =50.The multiple logistic regression model included age, height, weight, postmenopausal status, total hip BMD, and arm span (AS) or sitting height as explanatory variables. Akaike's information criterion (AIC) evaluated model goodness-of-fit. RESULTS: Age-adjusted AS and sitting height in subjects with and without vertebral deformities were 147.2+/-0.6 cm and 148.5+/-0.2 cm (P=0.055), 78.5+/-0.5 cm and 79.9+/-0.2 cm (P=0.007), respectively. Every 5-cm increase in AS indicated 1.5-fold increased risk of prevalent vertebral deformity in the model including age, height, weight, postmenopausal status, and BMD. Including the explanatory variable AS in models yielded better predictive accuracy than excluding AS (AIC, 441.7 vs 446.6, respectively). Sitting height did not significantly influence model predictive ability. CONCLUSION: Predictive accuracy of model for vertebral fracture including age, height, weight, postmenopausal status, and BMD improved when AS was added as an explanatory variable. Models to screen for asymptomatic vertebral fractures should include AS.

Biochemical markers of bone turnover may predict progression to osteoporosis in osteopenic women: the JPOS Cohort Study.

We evaluated the value of bone turnover markers, including osteocalcin (OC) and bone-specific alkaline phosphatase in the serum, and type I collagen C-terminal telopeptide and free and total deoxypyridinoline (tDPD) in the urine of fasting patients, in an attempt to predict which osteopenic women [i.e., those with > or = 70% and <80% of the young adult mean (YAM) bone mineral density (BMD)] would progress to the osteoporosis level of BMD (<70% of YAM). Of the 1153 women without defects in bone metabolism who completed the 3-year follow-up, 147, 161, and 144 women were judged by dual X-ray absorptiometry to be osteopenic from baseline measurements of BMD in the spine (LS), hip (TH), and distal radius (DR), respectively. Progression to the osteoporotic level of BMD was noted for 23.8%, 16.1%, and 12.5% of the subjects with osteopenia of the LS, TH, and DR, respectively, while most of them were in the lower half of the osteopenic level of BMD at baseline. Among the subjects in this lower-level osteopenia category, a significantly higher OC level was observed for the subjects with osteoporosis progression at the LS than those without. The subjects with progression at DR showed a significantly higher tDPD level. The association between OC level and disease progression remained unchanged after adjustments for age, body size, and BMD at baseline. The subjects in the upper one-third category of OC levels showed a 6.4 fold greater risk of progression at LS (95% confidence interval, 1.8-23.1) compared with those in the lower one-third category after the adjustments for age, body size, and BMD at baseline. Receiver operating characteristics analysis showed that the area under the curve was 0.716 for the OC level in the prediction of osteoporosis progression at LS. The levels of OC and tDPD may be useful in predicting which osteopenic women will progress to osteoporosis.

Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study.

Japanese fermented soybeans (natto in Japanese), which contain a large amount of menaquinone-7, may help prevent the development of osteoporosis. We assessed the possibility of an association between habitual natto intake and bone mineral density (BMD) and BMD change over time in healthy Japanese women who participated in a large representative cohort study (Japanese Population-based Osteoporosis Study: JPOS study). The BMD was measured at the spine, hip, and forearm in 944 women (20-79 y old) at baseline and at a follow-up conducted 3 y later. Dietary natto intake was assessed by a FFQ on both occasions. Additional covariates including age, height, weight, lifestyle factors, dietary calcium intake, and the intake of other soybean products, were also measured. The total hip BMD at baseline increased (P for trend = 0.0034) with increasing habitual natto intake in the postmenopausal women, although this was not the case at other skeletal sites. There were significant positive associations between natto intake and the rates of changes in BMD at the femoral neck (P < 0.0001) and at the distal third of the radius (P = 0.0002) in the postmenopausal women. The association in the femoral neck persisted even after adjusting for covariates. No significant association was observed between the intake of tofu or other soybean products and the rate of BMD change in the postmenopausal women. Natto intake may help prevent postmenopausal bone loss through the effects of menaquinone 7 or bioavailable isoflavones, which are more abundant in natto than in other soybean products.

Reference database of biochemical markers of bone turnover for the Japanese female population. Japanese Population-based Osteoporosis (JPOS) Study.

The present study was conducted as a part of the Japanese Population-based Osteoporosis (JPOS) Study to establish reference values on the biochemical markers of bone turnover in the general Japanese female population over an applicable age range. The study recruited 3250 women aged 15-79 years, randomly selected from five municipalities throughout Japan, and obtained measurements of serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP); free and total forms of immunoreactive deoxypyridinoline, free pyridinolines and type I collagen cross-linked C-terminal telopeptide (CTx) in urine; serum intact parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25 (OH)2D); and bone density at the spine, hip and distal forearm. After excluding subjects with apparent or suggested abnormalities affecting bone mass, 2535 (78%) subjects were further analyzed. The authors presented 5-year age-specific mean values of the markers and mean marker levels derived from women aged 30-44 years with normal bone density as a healthy young adult reference. Values of the markers decreased with increasing age before the age of 40, increased steeply among subjects in their 50s, and remained elevated in the elderly. Serum calcium, phosphorus, PTH and 1,25 (OH)2D levels were higher in postmenopausal women than in premenopausal women. However, 1,25 (OH)2D was lower among early postmenopausal subjects. The levels of OC, BAP, CTx, PTH and 1,25(OH)2D were significantly greater for women with osteoporosis than for those without. The diagnostic value of the markers was limited as the sensitivity and specificity ranged from 55% to 60%. These findings will aid health professionals in the correct assessment of bone turnover status in Japanese women over a wide range of age.

Ultrasound bone densitometry of the calcaneus, determined with Sahara, in healthy Japanese adolescents: Japanese Population-based Osteoporosis (JPOS) Study.

To establish the reference values for quantitative ultrasound (QUS) indices (speed of sound [SOS]), and broadband ultrasonic attenuation [BUA]) in healthy Japanese adolescents, and to evaluate the effects of age and body size on QUS in comparison with their effects on bone mineral density (BMD), 632 healthy adolescents aged 12 through 17 years recruited from a larger cohort study (Japanese Population-based Osteoporosis [JPOS] Study), were examined in terms of bone mass measurements by QUS at the calcaneus (Sahara; Hologic) and by dual-energy X-ray absorptiometry at the distal one-third radius and ultradistal forearm. We present sex- and age-specific mean values of the QUS and BMD indices. BMD increased significantly up to 17 years of age in males and up to 16 years in females. However, the age-related change in the QUS indices in males was not as clear as that seen for BMD and no age-related change in the QUS indices was observed in females. Significant positive correlation coefficients between BMD and body size were observed in both sexes even after adjusting for the effect of age. SOS showed no correlation with body size and BUA showed a positive but weak correlation with body size in both sexes. Thus, the relationships of age and body size to BMD and QUS were different from each other, even though the QUS indices had significant positive correlations with BMD, allowing for the effect of age.

Single nucleotide polymorphisms of thrifty genes for energy metabolism: evolutionary origins and prospects for intervention to prevent obesity-related diseases.

The "thrifty" genotype and phenotype that save energy are detrimental to the health of people living in affluent societies. Individual differences in energy metabolism are caused primarily by single nucleotide polymorphisms (SNPs), some of which promote the development of obesity/type 2 diabetes mellitus. In this review, four major questions are addressed: (1) Why did regional differences in energy metabolism develop during evolution? (2) How do genes respond to starvation and affluence? (3) Which SNPs correspond to the hypothetical "thrifty genes"? (4) How can we cope with disease susceptibility caused by the "thrifty" SNPs? We examined mtDNA and genes for energy metabolism in people who live in several parts of Asia and the Pacific islands. We included 14 genes, and the SNP frequencies of PPAR gamma 2, LEPR, and UCP3-p and some other genes differ significantly between Mongoloids and Caucasoids. These differences in SNPs may have been caused by natural selection depending on the types of agriculture practiced in different regions. Interventions to counteract the adverse effects of "thrifty" SNPs have been partially effective.