Serum branched-chain amino acid levels are associated with fracture risk in Japanese women.

AIM: Branched-chain amino acids (BCAAs) have been shown to exert beneficial effects on muscle and bone metabolism; however, no studies to date have investigated whether BCAAs have beneficial effects on bone fractures. Herein, we aim to prospectively investigate the relationship between serum BCAA concentrations and the occurrence of vertebral fractures (VFs) in Japanese women. METHODS: During the observation period (7.5 ± 6.1 years), 188 of 983 participants experienced VF. Kaplan-Meier analyses were conducted to examine time-dependent variations in the vertebral compression fracture occurrence rate. Patients were stratified into quartiles based on serum BCAA concentration for this analysis. RESULTS: The analysis results indicated that the group with the lowest BCAA level developed VFs significantly earlier and with a higher frequency than the other groups (P < 0.001). A Cox proportional hazards model showed that BCAA concentration was a significant risk factor for incident fracture, even after adjusting for possible confounding factors. A series of multiple regression analyses were performed to identify factors related to serum BCAA concentration, with the results identifying levels of glycated hemoglobin (P < 0.001), adiponectin (P < 0.001), and NOx (P = 0.011) as significant factors associated with serum BCAA. CONCLUSIONS: Overall, the present study revealed that a lower serum BCAA level was an independent risk factor for incident VF in postmenopausal women. Geriatr Gerontol Int 2024; 24: 603-608.

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.

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.

Development of a predictive model for vitamin D deficiency based on the vitamin D status in young Japanese women: A study protocol.

BACKGROUND: Vitamin D deficiency (VDD) is associated with an increased risk for lifestyle-related diseases. In Japan, VDD is quite prevalent in all age groups, with its high risk in young women. Furthermore, its association during pregnancy with gestational hypertension and low birth weight has also been reported. VDD can be diagnosed by serum 25-hydroxyvitamin D [25(OH)D] levels, which, however, is not suited for screening. Therefore, we will create a predictive model for serum 25(OH)D concentration and prevalence of VDD based on such data as region, sun exposure habit, and vitamin D intake in young women. METHODS: From 2020 to 2022, we conduct a cross-sectional study of 600 young women in four regions of Japan, identify the indices associated with serum 25(OH)D concentrations such as sun exposure habits, habitual vitamin D intake, ultraviolet-B irradiation, seasons (summer and winter) and latitude, and construct prediction models for serum 25(OH)D concentrations and VDD risk. This study has been registered with UMIN-CTR (ID: UMIN000041527). RESULTS: One hundred and fifteen subjects have been collected from 6 institutions in winter as of May 2021. When data from more than 200 subjects have become available, we will conduct the interim analysis, summarize the data by region and facility, review the inclusion criteria for analysis, and check for missing values and outliers. Prediction models for serum 25(OH)D concentration and VDD will be determined in the final analysis when all cases have been collected. CONCLUSIONS: A screening tool for VDD risk to be developed in our study based on the predictive model would help the public and medical professionals prevent lifestyle-related diseases through improving VDD. Additionally, the results may serve as the scientific basis for determining the appropriate vitamin D intake and sun exposure standards.

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.

The Intake of Kiwifruits Improve the Potential Antioxidant Capacity in Male Middle- and Long-Distance Runners Routinely Exposed to Oxidative Stress in Japan.

Oxidation damages cells and muscles, and thus, causes injuries and fatigue, which negatively affect the conditioning of athletes. Thus, in this study, we aimed to investigate the effects of high-antioxidant fruits (kiwifruit) intake on oxidative stress level (d-ROMs) and antioxidant activity (BAP) in male middle- and long-distance runners routinely exposed to oxidative stress. This study was performed from May to July 2017 (Study 1) and October to December 2018 (Study 2). The subjects in Study 1 were 30 male runners, of which 15 consumed two yellow kiwifruits (Zespri® SunGold Kiwifruit) per day for one month of the survey period (Intake group). The subjects of Study 2 were 20 male runners who had high d-ROMs from preliminary testing. These runners consumed two yellow kiwifruits (Zespri® SunGold Kiwifruit) per day for two months. d-ROMs and BAP were measured using a free radical analyzer. In study 1, the d-ROMs decreased while the potential antioxidant capacity (BAP/d-ROMs ratio) increased in the Intake group. In study 2, BAP/d-ROMs ratio was higher after one and two months compared to that at pre-intervention. Study findings suggested that consumption of kiwifruits may reduce oxidative stress levels and increase antioxidant activity, resulting in improved potential antioxidant capacity.

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 A intake is related to stress fracture occurrence in male collegiate long-distance runners.

BACKGROUND: Nutrient intake has an essential role in bone disorder prevention among long-distance runners. However, the influence of Vitamin A intake on the risk of stress fractures remains unknown. This prospective study aimed to investigate the association between Vitamin A intake, and stress fracture occurrence in male collegiate long-distance runners. METHODS: Forty-one male long-distance runners were recruited from a top-class long-distance college running team whose complete survey data on bone mass, anthropometric measurements, blood and urine tests, food intake frequency, history of competing in long-distance races, and monthly running distance during 2009-2010 were available. The influence of factors related to stress fractures, including Vitamin A intake, at baseline and the occurrence of stress fractures during the 1-year period were investigated. RESULTS: Four athletes experienced stress fractures during the study period (stress fracture group) and had significantly higher Vitamin A, calcium, and iron intake at baseline compared with that in the nonstress fracture group. In the stress fracture group, the mean daily Vitamin A intake was 2792 µg of retinol activity equivalents (RAE), which was higher than the upper intake limit for males aged 18-25 years in the Japanese Dietary Standard. Logistic regression analyses showed that only Vitamin A intake independently contributed to stress fracture occurrence. The odds ratio of developing stress fractures with a 100-µg RAE increase in Vitamin A intake was 1.22. CONCLUSIONS: A result of the present study suggested that Vitamin A intake was associated with stress fracture occurrence in male collegiate long-distance runners.

Attempt to Determine the Cut-Off Value of Serum Ferritin for Iron Deficiency in Male College Student Runners.

For the evaluation of iron nutrition status, the measurement of serum ferritin levels is the most convenient and widely used technique for estimating stored iron. However, the cut-off value of serum ferritin for iron deficiency in athletes has not yet established. This study aimed to determine the cut-off value of serum ferritin to define iron deficiency in male college student runners. This study included 37-43 Japanese male college student runners for each month. Anthropometric measurements and blood collection were conducted from March to December 2018. In all months except May, significant negative correlations were observed between serum ferritin and transferrin levels, total iron binding capacity (TIBC), and unsaturated iron binding capacity. Furthermore, a significant association between serum ferritin levels and TIBC was observed by nonlinear regression analysis. The curvature radius and curvature were calculated using the data from 9 mo, and serum ferritin levels with the smallest curvature radius and the highest curvature in each month were identified. The serum ferritin levels were as follows: 35.0 ng/mL in March, 45.0 ng/mL in April, 40.0 ng/mL in June, 35.0 ng/mL in July, 35.0 ng/mL in August, 35.0 ng/mL in September, 35.0 ng/mL in October, 35.0 ng/mL in November, and 40.0 ng/mL in December. The average value was 37.2 ng/mL. In conclusion, the cut-off value of serum ferritin for defining iron deficiency in runners was determined to be 40.0 ng/mL in this study. This value (40.0 ng/mL) may be useful for iron deficiency screening in runners.

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.

Calcium Intake and Bone Mineral Acquisition during the Pubertal Growth Spurt: Three-Year Follow-Up of the Kitakata Kids Health Study in Japan.

Calcium intake during a growth spurt may influence bone mineral acquisition. However, no population-based cohort studies have examined the relationship between calcium intake and whole-body bone mineral acquisition in Japanese children. The present study investigated the relationship between calcium intake and whole-body bone mineral acquisition in community-dwelling children in a northeast region of Japan using dual-energy X-ray absorptiometry. The source population for the baseline survey comprised all school children in 4th through 6th grades (275 children; age range, 10-12 y) in the Shiokawa area of Kitakata City, Fukushima. We obtained complete information from 220 children (100 girls and 120 boys), and analyzed total body less head (TBLH) bone mineral content (BMC), TBLH areal bone mineral density (aBMD), and bone mineral apparent density (BMAD) as an estimate of volumetric bone density. The Food Frequency Questionnaire for the Prevention and Management of Osteoporosis was validated in a previous study and used to estimate dietary nutrient intake. At baseline, mean calcium intake was 641 mg/d in girls and 660 mg/d in boys. Calcium intake in boys showed a significant (p<0.05) relationship with TBLH BMC and TBLH aBMD at follow-up, and with changes in TBLH BMC, TBLH aBMD, and TB BMAD from baseline to follow-up. After adjusting for potential confounding factors including body weight, we found no significant relationships between calcium intake and bone mineral parameters. Further studies are needed to clarify whether calcium intake affects bone mineral acquisition during pubertal growth spurts in the Japanese population.

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.

[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.

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.

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.

[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.

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.