Association between SLCO1B1 rs4149056 and tegafur-uracil-induced hepatic dysfunction in breast cancer.

Aim: The aim of this study was to identify pharmacogenomic biomarkers to predict tegafur-uracil (UFT)-induced liver dysfunction. Patients & methods: A total of 68 patients, who were administered UFT, were evaluated using a two-step pharmacogenomics analysis. Results: The first screening revealed the association between five SNPs and UFT-induced hepatic dysfunction. In the second step, SLCO1B1 (rs4149056) was found to be the only SNP associated with UFT treatment-related elevation of aspartate aminotransferase (odds ratio: C/C vs T/T = 7.8, C/T vs T/T = 5.7; p = 0.037) and alanine transaminase (odds ratio: C/C vs T/T = 12.2, C/T vs T/T = 4.1; p = 0.034) levels. Conclusion: The SLCO1B1 polymorphisms are possible predictors of UFT treatment-related hepatic dysfunction.

Optimal vitamin D intake for preventing serum 25-hydroxyvitamin D insufficiency in young Japanese women.

Populations of East Asian countries have been known to have low calcium intakes and low serum 25(OH)D concentrations, suggesting that Ca and vitamin D (VitD)-deficiencies are commonly observed. These nutritional imbalances may lead to low peak bone mass (PBM). The low PBM seen in Ca/VitD-deficient individuals may lead to osteoporosis, as well as an increased risk of fracture. A survey was conducted in young Japanese women (n = 296, 21.2 ± 2.3 years old) on their Ca/VitD intakes and serum 25(OH)D levels, which demonstrated a significant positive correlation between VitD intake and serum 25(OH)D levels (R 2 = 0.020, P = 0.016), and the proportion with serum 25(OH)D over 20 ng/mL was significantly increased with VitD intake (P = 0.013). Serum 25(OH)D was negatively correlated to serum intact parathyroid hormone (R 2 = 0.053, P < 0.001). On receiver operating characteristic curve analysis, the VitD intake threshold for maintaining 25(OH)D levels at 20 ng/mL or higher was 11.6 µg/day or greater. It was suggested that the recommended VitD intake allowance, defined in the Adequate Intakes as 5.5 µg/day, may not be sufficient to maintain serum 25(OH)D levels for bone health.

Relationship between skipping breakfast and bone mineral density in young Japanese women.

UNLABELLED: BACK GROUND AND AIMS: It is well known that insufficient nutrient intake leads to poor bone status. To find a simple evaluation method for prevention of nutrition intake disorder, a cross-sectional study with 275 healthy Japanese female students aged 19-25 was conducted. METHODS: Anthropometric parameters, bone mineral density (BMD) at lumbar and total hip, bone metabolic markers and physical activity were measured in study participants and the frequency of skipping meals (breakfast, lunch, supper), and absolute values for nutrient intakes were assessed using a Diet History Questionnaire. RESULTS: The frequency of skipping breakfast significantly correlate to total energy intake (ρ= -0.276, p<0.001). BMI, total intake of energy, intake of protein, intake of phosphate, and energy expenditure positively correlated significantly to BMD at lumbar and total hip (p<0.05) using simple linear regression. BMI (regression coefficient (b))=0.088, p<0.001), bone alkaline phosphatase (b= -0.050, p=0.012), total energy expenditure (b=0.019, p<0.001), and frequency of skipping breakfast (b= -0.018, p=0.048) were independent risk factors for lower total hip BMD by multiple regression analysis. The total hip BMD in participants who skipped breakfast three or more times was significantly lower than in those who did not skip breakfast (p=0.007). CONCLUSIONS: In conclusion, managing the frequency of skipping breakfast and reducing it to <3 times per week may be beneficial for the maintenance of bone health in younger women.

[Bone and joint diseases in children. Familial factors in osteoporosis: focus on bone mineral density and lifestyles. A study in two and three generations].

In preventing osteoporosis, an understanding of both the innate genetic and acquired environmental factors implicated in its pathogenesis is critically important. These two sets of factors interact with each other so closely that it is difficult to deal with each independently of the other. In our study, heritability for lumbar bone mineral density (BMD) between mother and daughter was estimated as 0.56 before menarche and 0.60 after menarche, suggesting that the genetic factors predominated over the environmental factors. At the same time, these values also suggest a not-so-small role for the environmental factors in determining lumbar BMD. Thus there is an important role suggested for medical intervention aimed at acquisition of BMD through management of lifestyle factors with familial phenotypic similarities in mind. It is suggested that the younger the candidate, the better the chance for intervention, and that consideration needs to be given to how best to intervene in the candidate before and after menarche or menopause during which estrogen secretion is seen to vary greatly.

Familial correlation of bone mineral density, birth data and lifestyle factors among adolescent daughters, mothers and grandmothers.

This study aimed to clarify the relationship between skeletal or lifestyle factors among Japanese daughter-mother, mother-grandmother and daughter-grandmother pairs. We performed a cross-sectional study in a cohort of Japanese adolescent daughters (12-18 years of age), their mothers (339 pairs) and grandmothers on their mothers' side (34 pairs). Gestational age, birth weight, age at menarche and presence of menarche or menopause were surveyed in the participants. Height, body weight and lumbar 2-4 bone mineral density (BMD) were measured. Dietary intake and current physical activity were assessed by using questionnaires. Gestational age and age at menarche were significantly correlated among daughters, mothers and grandmothers (P < 0.001). BMD was significantly correlated between daughters and mothers (P < 0.001), while it was not significantly correlated between daughters and grandmothers or between mothers and grandmothers. Dietary intake of calcium and vitamin D, and the frequency, duration and intensity of current physical activity were significantly correlated between daughters and mothers (P < 0.05), although no significant correlation was found between daughters and grandmothers, or between mothers and grandmothers. The parameters for exercise indicated a positive correlation for BMD in the daughters and the mothers, but not in the grandmothers. The results suggested that estrogen deficiency decreases familial correlation for BMD after menopause. Achieving high BMD through exercise may be important for prevention of postmenopausal osteoporosis in premenopausal low-height mothers.

Age-related distribution of bone and skeletal parameters in 1,322 Japanese young women.

We explored factors that could serve as indices for therapeutic intervention aimed at prevention of osteoporosis. In this cross-sectional study, we investigated the timing of peak bone mass (PBM) in 1,322 Japanese women aged 12-30 years old. We measured height, body weight, bone mineral density (BMD), bone mineral content (BMC), and bone area at the lumbar spine and total hip, as well as the blood markers calcium, phosphorus, and the bone metabolic markers bone alkaline phosphatase (BAP) and type I collagen cross-linked N-telopeptide (NTX). All measurements were standardized with the mean at age 18 defined as 100% to identify age-related differences. In the total hip, BMD peaked at age 18, while, in the lumbar spine, BMD peaked at age 29, of which 99.8% was attained at age 18, suggesting that peak BMD was attained at age 18 at both the total hip and lumbar spine. No age difference was observed in serum calcium, while there was a 15.1% decrease between ages 12 and 18 in serum phosphorus. There were 273.8% and 208.5% decreases in serum BAP and NTX, respectively, between ages 12 and 18, while these levels remained constant thereafter, suggesting that bone and calcium metabolism are constant between ages 19 and 30. Factors that had stronger correlations with BMD, BMC, and bone area from 12 years to 18 years were height and body weight. PBM was reached at age 18. Control of body weight by using total hip BMD as an index for intervention should be reasonable.

The impact of lifestyle factors on serum 25-hydroxyvitamin D levels: a cross-sectional study in Japanese women aged 19-25 years.

Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] lead to low bone mineral density (BMD) by increasing serum levels of intact parathyroid hormone (PTH), and are associated with a high mortality rate. Therefore, the 25(OH)D level is used as an indicator of frailty in older persons. To obtain higher serum 25(OH)D levels, management of lifestyle habits and nutrient intake is important beginning in a person's younger years. This study evaluated the degree of association between serum 25(OH)D concentrations and lifestyle factors in young Japanese women. A cohort study was conducted from December 2003, and the survey was finished by February 2004. The subjects were 274 Japanese women aged 19-25 years old. The parameters evaluated in these subjects included: (1) serum concentrations of 25(OH)D, intact PTH, calcium, and phosphorus; (2) BMD in the lumbar spine and hip; and (3) lifestyle factors (nutrient intake, physical activity, and duration of sunlight exposure). The serum 25(OH)D level was negatively associated with the intact PTH level (Spearman; r = -0.17, P = 0.006). The BMD was significantly higher in the high 25(OH)D and low intact PTH group than the other group (P < 0.05). The serum 25(OH)D level was significantly correlated with daily intake of dietary vitamin D (r = 0.20, P = 0.001), the mean number of steps taken per day (r = 0.16, P = 0.010) and the mean time spent in sedentary activity (r = -0.14, P = 0.018) among the lifestyle factors evaluated. Multiple regression analysis showed the degree of association between lifestyle factors and serum 25(OH)D to be small (R (2) = 0.084). Daily intake of dietary vitamin D and daily walking may be useful for increasing the serum 25(OH)D level in young Japanese women.

Variations in circulating osteoprotegerin and soluble RANKL during diurnal and menstrual cycles in young women.

BACKGROUND/AIMS: Physiological bone turnover shows diurnal variations and changes within the menstrual cycle. The aim of this study was to assess the variability of osteoprotegerin (OPG) and soluble RANKL (sRANKL) serum levels during diurnal and menstrual cycles. METHOD: Blood was collected from 15 young women at 6-hour intervals between 08.00 and 20.00 h during the follicular phase. Moreover, to compare the follicular and luteal phases, blood was also collected at 14.00 h during the luteal phase. Serum bone-specific alkaline phosphatase (BAP), N-telopeptide of type I collagen (NTX), OPG and free sRANKL were measured. RESULTS: No diurnal variations in BAP, OPG, sRANKL and sRANKL/OPG ratio were detected. NTX was significantly higher in the morning than in the afternoon and at night (p = 0.02). There were no menstrual variations in either. CONCLUSIONS: The consistent absence of diurnal variations in circulating OPG and sRANKL levels may reflect the absence of diurnal variation in their expression in the bone microenvironment. In this case, the nocturnal rise and the fall in bone resorption in the luteal phase should be accounted for by other factors than RANKL/OPG-mediated factors. Timing of sampling is unlikely to influence the results of circulating OPG and sRANKL measurement.

Influence of maternal genetic and lifestyle factors on bone mineral density in adolescent daughters: a cohort study in 387 Japanese daughter-mother pairs.

We conducted a cross-sectional study in a cohort of Japanese adolescent schoolgirls (12-18 years of age) and their mothers (387 pairs). Age, lumbar bone mineral density (BMD), birth and menarche-related status, height, body weight and lifestyles were surveyed in the participants. The values of BMD, height and body weight were converted to standard deviation (SD) by age. There were 49 (12.7%) pre-menarche and 338 (87.3%) post-menarche daughters. BMD-SD, height-SD, vitamin D intake and vitamin K intake were significantly correlated between the pre-menarche daughters and mothers (P < 0.05), while BMD-SD, birth weight, age at menarche and all lifestyle-related factors were significantly correlated between the post-menarche daughters and mothers (P < 0.05). BMD-SD in the pre-menarche daughters was affected by BMD-SD in mothers (R (2) = 0.069, P = 0.033) and their own height-SD (R (2) = 0.199, P = 0.001) (model R (2) = 0.340), independently. BMD-SD in the post-menarche daughters was affected by BMD-SD in mothers (R (2) = 0.073, P < 0.001) as well as by their own age at menarche (R (2) = 0.020, P = 0.001), height-SD (R (2) = 0.022, P < 0.001), body weight-SD (R (2) = 0.081, P < 0.001) and intensity of exercise (R (2) = 0.015, P = 0.045) (model R (2) = 0.372), independently. The results suggest that BMD is strongly correlated between daughters and mothers and that a greater age at menarche leads to lower peak bone mass. It was also suggested that maintaining high-intensity physical activity and adequate body weight is important in achieving maximum BMD as factors amenable to intervention in post-menarche daughters.

Possible risk factor for postmenopausal women: postprandial hypertriglyceridemia.

AIM: To explore the clinical implications of postprandial hypertriglyceridemia in postmenopausal Japanese women. METHODS: Postprandial blood samples were collected from 91 women at their initial visit, with fasting blood samples collected within the following month to examine their lipid profiles. These women were grouped into normotriglyceridemia (fasting/postprandial triglycerides [TG] < 150; n = 36), mild postprandial hypertriglyceridemia (fasting TG < 150, postprandial TG > or = 150, < 225; n = 27), moderate postprandial hypertriglyceridemia (fasting TG < 150, postprandial TG > or = 225; n = 19) and hypertriglyceridemia (fasting TG > or = 150; n = 9) by using 225 mg/dL as the cut-off value for postprandial hypertriglyceridemia. RESULTS: The subjects were 54.1 +/- 7.8 years old; their duration of menopause, 6.0 +/- 7.7 years; body mass index, 21.4 +/- 4.0 kg/m(2); postprandial TG concentration, 189 +/- 110 mg/dL; and fasting TG concentration, 109 +/- 50 mg/dL. Approximately 50% (n = 46) of the women had normal fasting TG (fasting TG < 150), but high postprandial TG (postprandial TG > or = 150). Approximately 10% (n = 9) of the women had hypertriglyceridemia (fasting TG > or = 150 mg/dL). In those with postprandial hypertriglyceridemia (n = 46), postprandial TG negatively correlated with high-density lipoprotein cholesterol (HDL-C), while fasting TG showed no such correlation with HDL-C. CONCLUSION: Postprandial TG may provide a better understanding of lipid metabolism in postmenopausal women.

Effect of physical activity and nutrition on bone mineral density in young Japanese women.

We explored factors that contributed to bone mineral density (BMD) in Japanese young women by quantifying the factors related to BMD. Between October 2003 and February 2004, we conducted a cross-sectional survey to study the status of nutritional intake and physical activity, and evaluated the various physical and serum parameters in relation to BMD. Subjects included 254 healthy female students who were 19-25 years old and were attending the Nursing School of Tokyo Women's Medical University, Japan. We measured the lumbar BMD (L2-L4) in these women. Multiple regression analysis was used to predict factors that contributed to current L2-L4 BMD. Our results showed that body mass index (BMI) (standardized regression coefficient = 0.45, P < 0.0001), past exercise habit (standardized regression coefficient = 0.15, P < 0.0059), and current total energy expenditure (standardized regression coefficient = 0.12, P < 0.03) were factors that significantly predicted the current L2-L4 BMD, with BMI as a key contributing factor. A BMI of 20.8 kg/m(2) allowed acquisition of young adult mean (YAM) irrespective of the total energy expenditure. In subjects with low BMI, L2-L4 BMD increased with higher current energy expenditure. A BMI of 20.8 kg/m(2) or greater and an energy expenditure of 32.9 METS-h/day or greater are required to acquire the YAM. We concluded that BMI and physical activity were factors that affected the BMD of Japanese young women.