Development of a predictive scoring system for vitamin D deficiency 'Vitamin D Deficiency Predicting Scoring (ViDDPreS)' based on the vitamin D status in young Japanese women: a nationwide cross-sectional study.

OBJECTIVE: Vitamin D deficiency (VDD) is common among young women and causes various health problems, including those that occur during pregnancy and childbirth. Thus, we investigated the risk factors for VDD in young Japanese women and developed a simple risk scoring system called Vitamin D Deficiency Predicting Scoring (ViDDPreS). DESIGN: A cross-sectional study, using the following factors for multivariate logistic regression analysis to create the ViDDPreS score: residential area, season, cumulative ambient ultraviolet-B irradiation, BMI, vitamin D supplement use, sun exposure habits, frequency of habitual food intake and eating habits. The subjects were randomly divided into development and test sets for analysis. Serum 25-hydroxivitamin D concentration of less than 20 ng/ml was defined as VDD. SETTING: Four regions (Hokkaido/Tohoku, Kanto, Chubu/Kinki/Shikoku and Kyushu/Okinawa) in Japan. PARTICIPANTS: Five hundred and eighty-three healthy women aged 18-40 years. RESULTS: In the development set, the VDD group (68·4 %) had higher proportions of the following variables than the non-VDD group: residential area outside the Kanto region; blood samples obtained in winter; low BMI (<18·5 kg/m2); vitamin D supplement non-users; short time regularly spent outside on weekdays; intake of fish, vitamin D-abundant fish, dried fish and redfish less than once a week. VDD risk was classified as low, medium or high according to the ViDDPreS scores including these contributing factors, with a test set C-index of 0·671. CONCLUSION: We identified the risk factors for VDD in young Japanese women and developed a simple risk scoring system that enables us to assess VDD risk and aid in the development of appropriate prevention and treatment strategies for this population.

Distinct dietary risk factors for incident osteoporotic fractures in early and late postmenopausal phase women.

INTRODUCTION: Available evidence on favorable nutritional factors for preventing osteoporosis remains controversial. Considering the recent increases in life expectancy, we investigated the relationship between incident osteoporotic fractures and dietary habits in early and late postmenopausal phase women. MATERIALS AND METHODS: Subjects were Japanese postmenopausal outpatients recruited at a primary care institution in Nagano Prefecture (Nagano Cohort Study). Patients with critical or acute illness or secondary osteoporosis were not included in this study. In total, 1,071 participants were prospectively followed for a mean of 5.8 years. The cohort was divided into early (≤ 70 years) and late (> 70 years) postmenopausal phases based on median age. Dietary nutrient intake was estimated by the food frequency questionnaire method. According to baseline nutrient intake characteristics, we focused on protein/energy and Ca/NaCl intake ratios, which were also divided by the median values. RESULTS: Kaplan-Meier plots revealed a significantly higher occurrence of fractures for the high protein/energy intake group in early postmenopausal subjects (P = 0.009), whereas the low Ca/NaCl intake group in late postmenopausal subjects exhibited a significantly earlier occurrence of fractures (P = 0.002). Multivariate Cox regression uncovered significant independent risks of higher protein/energy (HR 1.35; 95% CI 1.04-1.74) and lower Ca/NaCl (HR 0.79; 95% CI 0.63-0.99) intake ratios for incident osteoporotic fractures in the early and late postmenopausal cohorts, respectively. CONCLUSION: Distinct dietary risk factors for osteoporotic fractures were identified in early and late postmenopausal phase women. Appropriate nutritional guidance according to patient age will be important for maintaining bone health and quality of life.

Association between trunk-to-peripheral fat ratio and renal function in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

BACKGROUND: Central obesity as measured by waist-to-hip circumference ratio (WHR) has been reported to be associated with renal hemodynamics and function. However, the adipose component of WHR, which is a composite measure of fat mass and fat-free mass, is small, particularly in nonobese subjects. Trunk-to-peripheral fat ratio as measured using dual-energy absorptiometry (DXA) is a more precise method for evaluating central fat distribution than WHR. The present study investigated the cross-sectional association between DXA-measured trunk-to-peripheral fat ratio and estimated glomerular filtration rate (eGFR) in community-dwelling elderly Japanese men. METHODS: Participants were 575 men aged ≥65 years at the time of the baseline survey of the second Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. 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: eGFR values significantly decreased from the lowest to the highest quintile of TAR/TLR. After adjusting for potential confounding factors including whole-body fat, the highest quintile of both TAR and TLR showed statistically significant odds ratios for the risk of eGFR <60 ml/min/1.73 m2, relative to the lowest quintile. In addition, a significant decreasing trend was observed for eGFR values from the lowest to the highest quintile of TAR/TLR after adjusting for confounding factors including whole-body fat. CONCLUSION: Elderly men with a large trunk-to-peripheral fat ratio tended to have a lower eGFR. This association occurred independently of that between whole-body fat and eGFR.

Associations between trunk-to-peripheral fat ratio and cardiometabolic risk factors in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

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.

Vitamin K intake and health, consideration from the epidemiological studies.

The most fundamental function of vitamin K is to activate the blood coagulation factors in the liver. Despite the recent recognition of its extra-hepatic actions, the current Dietary Reference Intakes for vitamin K is based on the amount necessary for maintaining the normal blood coagulation in many countries. To define the Dietary Reference Intake for vitamin K, appropriate biomarkers well-reflecting the vitamin K status are essential. Unfortunately, however, no markers are currently available with properties enabling us to properly define the vitamin K status; i.g., no interference by other factors and the presence of widely approved cut-off values. Thus, Adequate Intake is determined, which is an index based on the representative dietary intake data from healthy individuals. Recently, epidemiological studies have been reported regarding the relationship between vitamin K and noncommunicable diseases including osteoporotic fracture. Furthermore, studies focusing on the relationship between vitamin K intake and metabolic syndrome, physical function, depression, cognition, and all-cause mortality have become available, although limited in number. This review summarizes the recent findings in favor of the novel functions of vitamin K. More epidemiological studies are needed to define the appropriate vitamin K intake value based on the prevention of various disorders.

25-Hydroxyvitamin D profiles and maternal bone mass during pregnancy and lactation in Japanese women.

Vitamin D deficiency is observed worldwide and represents a health hazard for mothers, infants and elderly persons. We know that many young Japanese women experience vitamin D insufficiency; however, there is a lack of knowledge regarding the serum 25-hydroxyvitamin D [25(OH)D] profile of pregnant Japanese women and of the association between maternal 25(OH)D level and maternal bone mass during pregnancy and lactation. In this longitudinal study, 160 pregnant Japanese women were enrolled; of them, 68 have been followed-up from the first trimester through at least 1 year of breast-feeding. We estimated serum 25(OH)D levels, intact PTH levels, calcaneus quantitative ultrasound (QUS: T score) scores, bone mineral density at the distal one-third of the radius, dietary intakes according to the Food Frequency Questionnaire, and sunlight exposure times. We found that Vitamin D deficiency is prevalent in Japanese women, irrespective of pregnancy or lactation, and our analysis suggested that 25(OH)D levels and BMI in the first trimester were related to the lactating women's bone mass from after delivery to 1 year after delivery.

Executive summary of clinical practice guide on fracture risk in lifestyle diseases.

Accumulating evidence has shown that patients with lifestyle diseases such as type 2 diabetes mellitus, chronic kidney disease, and chronic obstructive pulmonary disease are at increased risk of osteoporotic fracture. Fractures deteriorate quality of life, activities of daily living, and mortality as well as a lifestyle disease. Therefore, preventing fracture is an important issue for those patients. Although the mechanism of the lifestyle diseases-induced bone fragility is still unclear, not only bone mineral density (BMD) reduction but also bone quality deterioration are involved in it. Because fracture predictive ability of BMD and FRAX® is limited, especially for patients with lifestyle diseases, the optimal management strategy should be established. Thus, when the intervention of the lifestyle diseases-induced bone fragility is initiated, the deterioration of bone quality should be taken into account. We here review the association between lifestyle diseases and fracture risk and proposed an algorism of starting anti-osteoporosis drugs for patients with lifestyle diseases.

Trunk-to-peripheral fat ratio predicts a subsequent blood pressure in normal-weight pubertal boys: a 3-year follow-up of the Kitakata Kids Health Study.

BACKGROUND: Limited evidence exists regarding the relationship between central-to-peripheral fat ratio measured by dual-energy X-ray absorptiometry (DXA) and subsequent cardiometabolic risk in both pediatric and adult populations. METHODS: The present cohort study investigated the relationship between DXA-measured body fat distribution and cardiometabolic parameters. The source population was 275 4th-6th graders (aged 9.6-12.6 years) in the northeast region of Japan (Shiokawa area in Kitakata). A 3-year follow-up was conducted to obtain complete information from 155 normal-weight children (87 boys and 68 girls). Normal-weight children were identified using sex- and age-specific international cut-offs for body mass index (BMI) based on adult BMI values of 25 kg/m2 and 18.5 kg/m2, respectively. Body fat distribution was assessed using the trunk-to-appendicular fat ratio (TAR) and trunk-to-leg fat ratio (TLR) measured by DXA. RESULTS: In boys, systolic blood pressure (SBP) at follow-up showed a significant relationship with TAR at baseline after adjusting for age, height, pubic hair appearance, SBP, and whole body fat at baseline (ß = 0.24, P < 0.05), and SBP also showed a significant relationship with TLR after adjusting for confounding factors including whole body fat (ß = 0.25, P < 0.05). In girls, there were no significant relationships between blood pressure and TAR/TLR. CONCLUSION: Body fat distribution in normal-weight boys predicted subsequent blood pressure levels in adolescence. The relationship between fat distribution and blood pressure was independent of fat volume.

Bisphosphonates prevent age-related weight loss in Japanese postmenopausal women.

Decline of body weight with aging is a major risk factor for frailty, osteoporosis and fracture, suggesting that treatment for osteoporosis may affect body composition. Recently, we have shown that 5-year treatment with raloxifene prevented age-related weight loss, suggesting some other drugs for osteoporosis may also prevent a decrease in body weight with aging. The present study aimed to identify the relationship between bisphosphonate treatment and body composition markers. We measured bone mineral density (BMD), body composition, and bone remodeling markers in 551 Japanese postmenopausal women with bisphosphonate treatment, which included risedronate or alendronate treatment (BP-treatment group; N = 193) and without treatment by any osteoporosis drug (no-treatment group; N = 358) for 4-7 years (mean observation periods; 5.5 years) and analyzed the relationship of these with BMD, body mass index (BMI), body weight, and biochemical markers. The mean (SD) age of the participants was 68.6 (9.8) years in the BP-treatment group and 63.7 (10.6) years in the no-treatment group. Percent changes in body weight and BMI were significantly different between the BP-treatment and no-treatment groups (P < 0.01 and P < 0.01, respectively). In multiple linear regression analysis, bisphosphonate treatment was a significant independent determinant of percent changes in body weight and BMI (P < 0.01 and P = 0.01, respectively). Long-term use of bisphosphonates prevented reductions in BMI and body weight, usually observed in elderly women. Our results suggest that bisphosphonate treatment not only reduces the risk for incident osteoporotic fractures but also for frailty in the elderly.

Low serum osteocalcin concentration is associated with incident type 2 diabetes mellitus in Japanese women.

Increasing evidence suggests that osteocalcin is involved in the regulation of glucose homeostasis. However, the relationship between serum osteocalcin levels and risk of incident type 2 diabetes mellitus is not clear. The objective of this study is to investigate whether serum osteocalcin levels are associated with the risk of incident type 2 diabetes mellitus. This study included 1691 Japanese postmenopausal women, 61 incident diabetes cases, and 1630 non-diabetic control subjects in the observation period. Baseline concentrations of intact osteocalcin, HbA1c, bone-specific alkaline phosphatase, adiponectin, leptin, urinary N-telopeptides were assessed. Serum osteocalcin levels were significantly correlated with HbA1c levels among 1691 Japanese postmenopausal women (R = -0.12, P < 0.0001). In receiver operating characteristic curve analysis, the optimal cut-off levels for serum osteocalcin to predict the development of type 2 diabetes mellitus was 6.1 ng/mL. The group with baseline osteocalcin levels <6.1 ng/mL showed a significantly higher risk for developing diabetes than the group with baseline osteocalcin levels >6.1 ng/mL (log-rank test, P  <  0.0001) during the mean observation period (7.6 ± 6.1 years; mean ± SD). In multiple Cox proportional hazard analysis, osteocalcin levels were significantly associated with development of type 2 diabetes mellitus during the observation period. Our results indicate that a decrease in serum osteocalcin levels is associated with future development of type 2 diabetes mellitus independent of conventional risk factors in Japanese postmenopausal women.

[Milk, Daily products and Bone health.Milk, Daily products and Bone health.Dietary Reference Intakes of Calcium by age group.]

The amount of calcium in the body changes with age. According to the Dietary Reference Intakes for Japanese(2015), the required amount of calcium is calculated by a factor addition method in consideration of the amount of calcium accumulated in the body, the amount excreted in urine, and percutaneous losses. At that time, the calcium absorption rate becomes a very important factor. Numerical values are set so as to increase the amount of calcium in the body during the growth phase in order to maintain the calcium content in the body after adulthood. Based on the available evidence, the calcium intake level of Japanese is low and needs to be increased.

[Milk, Daily products and Bone health.Milk intake and Bone acquisition in junior high school and high school students.]

The junior high school and high school years are the periods during which development spurts occur, and bone mass increases including height and weight. The bone mass gain at this time has a big influence on the maximum bone mass, which also leads to prevention of future osteoporosis. Calcium intake is important for bone mass acquisition, but there is a divergence between the value indicated by the meal intake standard and the actual intake amount, and efforts to increase the calcium intake amount are necessary. From the results obtained by providing milk with school lunch, the significance of drinking milk as a source of calcium at this time is particularly large.

Preventive effects of raloxifene treatment on agerelated weight loss in postmenopausal women.

Decline of body weight and body mass index (BMI) with aging is a major risk factor for osteoporosis and fracture, suggesting that treatment for osteoporosis may affect body composition. However, the effects of treatment for osteoporosis on body composition are not well known. The present study aimed to identify the relationship between raloxifene treatment and body composition markers. We measured bone mineral density (BMD), body composition, and bone remodeling markers in 236 Japanese postmenopausal women with raloxifene treatment (N = 50) and without treatment by any osteoporosis drug (N = 186) for 5 years and analyzed the relationship of these with BMD, BMI, body weight, and biochemical markers. The mean (SD) age of the participants was 65.5 (9.3) years. Percent-changes in body weight and BMI were significantly different between women taking raloxifene and those not taking any osteoporosis drugs (P = 0.03 and 0.048, respectively). Raloxifene treatment was a significant independent determinant of body weight and BMI. Long-term treatment with raloxifene prevents age-related weight loss.

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.

[Update on recent progress in vitamin D research. Eldecalcitol and intestinal calcium absorption.]

Though various physiological actions have been attributed to vitamin D, its most important function is to promote absorption of calcium from the intestinal tract. While the absorption rate of calcium is generally low, it tends to decline further with age. In addition, calcium intake is decreasing in recent years in Japan. Therefore, it is important to increase the intestinal calcium absorption rate. Eldecalcitol has been shown to increase calcium absorption from the intestinal tract, suppress bone resorption, increase bone mineral density, and prevent fractures. Elocalcitol use leads to a lower systemic active vitamin D[1α,25(OH)2D]concentration, compared to that with alfacalcidol use. This is because eldecalcitol inhibits vitamin D activation in the kidney. Therefore, it is presumed that the calcium absorption-boosting effect of eldecalcitol is not due to the action of 1α, 25(OH)2D, but due to eldecalcitol itself.

Association between vitamin D status and serum parathyroid hormone concentration and calcaneal stiffness in Japanese adolescents: sex differences in susceptibility to vitamin D deficiency.

There is currently insufficient information on serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and bone mineral status in healthy adolescents to allow reference values to be set. This study aimed to provide comparable data on vitamin D status in Japanese adolescents and to assess sex differences in susceptibility to vitamin D insufficiency. Serum 25OHD and PTH concentrations were measured in 1,380 healthy adolescents (aged 12-18 years). Subjects completed a questionnaire on exercise history, diet, and lifestyle factors. Calcaneal stiffness was evaluated by quantitative ultrasound. Serum 25OHD concentrations in boys and girls were 60.8 ± 18.3 and 52.8 ± 17.0 nmol/L, respectively. Approximately 30 % of boys and 47 % of girls had suboptimal 25OHD concentrations (<50 nmol/L). Serum PTH concentration was negatively correlated with serum 25OHD concentration in boys, but negatively correlated with calcium intake rather than serum 25OHD in girls. In contrast, the increment in calcaneal stiffness as a result of elevation of serum 25OHD was higher in girls than in boys. As vitamin D deficiency is common in Japanese adolescents, it was estimated that intakes of ≥12 and ≥14 µg/day vitamin D would be required to reach 25OHD concentrations of 50 nmol/L in boys and girls, respectively. Moreover, the results of the present study indicate that vitamin D deficiency has a greater association with calcaneal stiffness in girls than in boys.

Ability of self-reported estimates of dietary sodium, potassium and protein to detect an association with general and abdominal obesity: comparison with the estimates derived from 24 h urinary excretion.

As under-reporting of dietary intake, particularly by overweight and obese subjects, is common in dietary surveys, biases inherent in the use of self-reported dietary information may distort true diet-obesity relationships or even create spurious ones. However, empirical evidence of this possibility is limited. The present cross-sectional study compared the relationships of 24 h urine-derived and self-reported intakes of Na, K and protein with obesity. A total of 1043 Japanese women aged 18-22 years completed a 24 h urine collection and a self-administered diet history questionnaire. After adjustment for potential confounders, 24 h urine-derived Na intake was associated with a higher risk of general obesity (BMI≥25 kg/m2) and abdominal obesity (waist circumference≥80 cm; both P for trend=0·04). For 24 h urine-derived protein intake, positive associations with general and abdominal obesity were observed (P for trend=0·02 and 0·053, respectively). For 24 h urine-derived K intake, there was an inverse association with abdominal obesity (P for trend=0·01). Conversely, when self-reported dietary information was used, only inverse associations between K intake and general and abdominal obesity were observed (P for trend=0·04 and 0·02, respectively), with no associations of Na or protein intake. In conclusion, we found positive associations of Na and protein intakes and inverse associations of K intake with obesity when using 24 h urinary excretion for estimating dietary intakes. However, no association was observed based on using self-reported dietary intakes, except for inverse association of K intake, suggesting that the ability of self-reported dietary information using the diet history questionnaire for investigating diet-obesity relationships is limited.

Adherence to the food-based Japanese dietary guidelines in relation to metabolic risk factors in young Japanese women.

While Japanese diets have attracted considerable attention because of, for example, the long-life expectancy in Japan, their health benefits have not been examined. In the present study, we cross-sectionally examined whether adherence to the food-based Japanese dietary guidelines is associated with metabolic risk factors in 1083 Japanese women aged 18-22 years. Based on the Japanese Food Guide Spinning Top, adherence to the food-based Japanese dietary guidelines was assessed using dietary information on consumed servings of grain dishes, vegetable dishes, fish and meat dishes, milk and fruits and energy from snacks and alcoholic beverages during the preceding month, which was derived from a comprehensive diet history questionnaire. Higher dietary adherence was associated with higher intakes of protein, carbohydrate, dietary fibre, Na, K and vitamin C, and lower intakes of total and saturated fat. There was also an inverse association between dietary adherence and dietary energy density. After adjustment for potential confounding factors, dietary adherence was inversely associated with waist circumference (P for trend = 0·002). It also showed an inverse association with LDL-cholesterol concentrations (P for trend = 0·04). There was no association with the other metabolic risk factors examined, including BMI, systolic and diastolic blood pressure, total and HDL-cholesterol, TAG, glucose, glycated Hb and insulin concentrations. In conclusion, higher adherence to the food-based Japanese dietary guidelines, which was characterised by favourable dietary intakes of foods and nutrients as well as lower energy density, was associated with lower waist circumference and LDL-cholesterol concentrations in this group of young Japanese women.

[Bone and Nutrition. Calcium intake and bone health].

Calcium is undoubtedly an essential nutrient. Many studies have confirmed a significant relationship between the intake of calcium, and bone quantity and density. With regard to Japanese dietary reference intake values, the reference calcium intake values have been determined while considering bone quantity. However, a correlation between calcium intake and bone fractures has not been established. In osteoporosis treatment and prevention guidelines, the recommended calcium preparation grade for osteoporosis treatment has been set at a low level. However, to ensure appropriate effectiveness of osteoporosis treatment, it is necessary to take an appropriate amount of calcium. In recent years, the calcium intake level for Japanese people has tended to decline, which emphasizes the need for taking an appropriate amount of calcium in the diet.