Effect of low-dose calcium supplements on bone loss in perimenopausal and postmenopausal Asian women: a randomized controlled trial.

Current standard-dose calcium supplements (eg, 1000 mg/d) may increase the risk for cardiovascular events. Effectiveness of lower-dose supplements in preventing bone loss should thus be considered. This study aimed to assess whether calcium supplements of 500 or 250 mg/d effectively prevent bone loss in perimenopausal and postmenopausal Japanese women. We recruited 450 Japanese women between 50 and 75 years of age. They were randomly assigned to receive 500 mg of calcium (as calcium carbonate), 250 mg of calcium, or placebo daily. Medical examinations conducted three times over a 2-year follow-up period assessed bone mineral density (BMD) of the lumbar spine and femoral neck. One-factor repeated measures ANOVA was used for statistical tests. Subgroup analyses were also conducted. Average total daily calcium intake at baseline for the 418 subjects who underwent follow-up examinations was 493 mg/d. Intention-to-treat analysis showed less dramatic decreases in spinal BMD for the 500-mg/d calcium supplement group compared to the placebo group (1.2% difference over 2 years, p = 0.027). Per-protocol analysis (≥80% compliance) revealed that spinal BMD for the 500-mg/d and 250-mg/d calcium supplement groups decreased less than the placebo group (1.6%, p = 0.010 and 1.0%, p = 0.078, respectively), and that femoral neck BMD for the 500-mg/d calcium supplement group decreased less relative to the placebo group (1.0%, p = 0.077). A low-dose calcium supplement of 500 mg/d can effectively slow lumbar spine bone loss in perimenopausal and postmenopausal women with habitually low calcium intake, but its effect on the femoral neck is less certain. Calcium supplementation dosage should thus be reassessed. (Clinical Trials Registry number: UMIN000001176).

Nutritional and biochemical parameters associated with 6-year change in bone mineral density in community-dwelling Japanese women aged 69 years and older: The Muramatsu Study.

OBJECTIVE: Predictors of bone loss in elderly Asian women have been unclear. This cohort study aimed to assess lifestyle, nutritional, and biochemical predictors of bone loss in elderly Japanese women. METHODS: Subjects included 389 community-dwelling women aged 69 y and older from the Muramatsu cohort initiated in 2003; follow-up ended in 2009. We obtained data on physical characteristics, osteoporosis treatment (with bisphosphonates or selective estrogen receptor modulators), physical activity, calcium intake, serum 25-hydroxyvitamin D, undercarboxylated osteocalcin, serum albumin, and bone turnover markers as predictors. The outcome was a 6-y change in forearm BMD (ΔBMD). Osteoporosis treatment was coded as 0 for none, 1 for sometimes, and 2 for always during the follow-up period. Stepwise multiple linear regression analysis was used to identify independent predictors of ΔBMD. RESULTS: Mean age of the subjects was 73.3 y. Mean values of ΔBMD and Δweight were -0.019 g/cm(2) (-5.8%) and -2.2 kg, respectively. Stepwise multiple linear regression analysis revealed baseline BMD (ß = -0.137, P < 0.0001), osteoporosis treatment (ß = 0.0068, P = 0.0105), serum albumin levels (ß = 0.0122, P = 0.0319), and Δweight (ß = 0.0015, P = 0.0009) as significant independent predictors of ΔBMD. However, none of the other nutritional or biochemical indices were found to be significant predictors of ΔBMD. CONCLUSIONS: Our findings indicate that adequate general nutrition and appropriate osteoporosis medication, rather than specific nutritional regimens, may be effective in preventing bone loss in elderly women.

Social network disruption as a major factor associated with psychological distress 3 years after the 2004 Niigata-Chuetsu earthquake in Japan.

OBJECTIVES: The 2004 Niigata-Chuetsu earthquake of Japan caused a great deal of damage, and people living in the affected region are still struggling to reconstruct their lives. The aim of this study was to determine factors associated with psychological distress in people living in a town at the epicenter 3 years after the earthquake. METHODS: We conducted a cross-sectional study from June 2007 to January 2008. Participants included 225 individuals living in Kawaguchi (age ≥20 years) who reported psychological symptoms. Information on family structure, employment status, alcohol use, social network, and extent of house damage was elicited by public health nurses conducting structured interviews. Levels of psychological distress were assessed with the Kessler Psychological Distress Scale (K10), with a K10 score ≥25 defined as psychological distress. RESULTS: The mean age of participants was 66.1 ± 12.9 years. The prevalence of psychological distress varied among different employment classes, being 5/73 (6.8%) for participants with paid employment, 12/50 (24.0%) for full-time housewives, and 11/101 (10.9%) for those who were unemployed (χ(2) = 8.42, P = 0.015). It also varied between participants who had lost contact with people in the community and those who had no change in social contact [9/20 (45.0%) vs. 19/189 (10.1%), respectively; χ(2) = 19.04, P < 0.001]. Multiple logistic regression analysis showed that age [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.91-0.98], poor or loss of contact with people in the community (OR 6.97, 95% CI 1.85-26.2), and lack of employment (full-time housewives or unemployed individuals) (OR 6.74, 95% CI 1.62-28.0) were associated with psychological distress. CONCLUSIONS: People who lose their social network are at a very high risk for post-earthquake psychological distress and require appropriate care.

Physical activity and 5-year changes in physical performance tests and bone mineral density in postmenopausal women: the Yokogoshi Study.

OBJECTIVE: The effect of physical activity on musculoskeletal health in older adults is not completely understood. The aim of this study was to determine the relationship between physical activity and 5-year changes in physical performance tests and bone mineral density (BMD) in postmenopausal women. STUDY DESIGN: The design was a 5-year cohort study. MAIN OUTCOME MEASURES: Subjects were 507 women (55-74 years old) living in a rural community in Japan. Physical activity assessed included housework, farm work, and moderate leisure-time physical activity within the previous week. Measurements at baseline included handgrip strength, walking time (timed "Up & Go" test) and BMD of the femoral neck and vertebrae. Five-year changes in these measures (outcome variables) were compared among groups with different levels of physical activity by analysis of covariance. RESULTS: Women who did not do housework performed worse in changes in handgrip strength (difference=2.22 kg, P=0.0201) and worse in changes in the walking time (difference=0.54 s, P=0.0072) than those who did housework alone. Women who spent at least 9h per week (median=24) doing farm work performed better in changes in handgrip strength (difference=0.28 kg, P=0.0334), but worse in changes in the walking time (difference=0.66 s, P<0.0001) than those who did not do farm work. However, leisure-time activity was not associated with changes in any outcome variable, and none of the physical activities predicted BMD changes. CONCLUSIONS: Engaging in housework and farm work are determinants of physical function in postmenopausal women, which may help them maintain independence in daily living.

Mutagenicity and mutagens of the red chili pepper as gallbladder cancer risk factor in Chilean women.

High consumption of red chili pepper has been shown to be a risk factor for gallbladder cancer (GBC) in Chilean women with gallstones, and included mutagens may be important in this context. We aimed to investigate the mutagenicity and mutagens in Chilean red chili pepper in the Ames test using Salmonella typhimurium strains TA98, TA1537, TA100, and TA1535 with and without metabolic activation (S9 mix). Pure capsaicin was tested for mutagenicity using strain TA98. The presence of aflatoxins was evaluated by two-dimensional thin layer chromatography, and then the concentrations of aflatoxins B1, B2, G1, and G2 were measured by an HPLC system. In strain TA98, the mean numbers of revertant colonies with and without the S9 mix were 2.5- and 2.2-fold higher than those of each negative control, respectively. However, pure capsaicin did not show mutagenic activity in strain TA98. Aflatoxin contamination of red chili pepper was confirmed, and the concentrations of aflatoxins B1 and G1 were 4.4 ng/g and 0.5 ng/g, respectively. Our findings suggest that low-level but protracted exposure to aflatoxins may be associated with the development of GBC in Chilean women who carry gallstones.

Evidence that genetic variants of metabolic detoxication and cell cycle control are not related to gallbladder cancer risk in Chilean women.

BACKGROUND AND AIMS: High consumption of red chili pepper has been shown to be a risk factor for gallbladder cancer (GBC) in Chilean women. However, genetic factors in addition to this and other environmental factors may also be associated with an increased risk of GBC. We aimed to examine the associations of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase class mu (GSTM1), and tumor protein p53 (TP53) polymorphisms with the risk of GBC in Chilean women. METHODS: A hospital-based case-control study of 57 patients with GBC, 119 patients with gallstones, and 70 controls was conducted. The statuses of the polymorphisms CYP1A1 rs4646903, CYP1A1 rs1048943, and TP53 rs1042522 were assayed using Custom Taqman SNP Genotyping Assays and TaqMan SNP Genotyping Assay. GSTM1 deletion polymorphism was detected by allele-specific PCR analysis. RESULTS: No significant differences in the genotypic or allelic frequencies in the CYP1A1, GSTM1, and TP53 polymorphisms were found between the three groups. CONCLUSION: These genetic variants were not related to an increased risk of GBC in Chilean women. Other polymorphisms, such as red-chili-pepper-related polymorphisms, may contribute to the development of GBC in Chilean women.

Long-term suicide mortality rates decrease in men and increase in women after the Niigata-Chuetsu earthquake in Japan.

A devastating earthquake causes psychological distress, and may increase suicide mortality thereafter, yet previous studies have made inconsistent conclusions regarding this issue. The purpose of the present study was to determine whether the 2004 Niigata-Chuetsu earthquake in Japan affected long-term mortality from suicide. We conducted a comparative study of suicide mortality rates during the 5-year period preceding and the 3-year period following the earthquake in the disaster area and a control area in Niigata Prefecture, by analyzing death certificate data from October 1, 1999, to September 30, 2007. In men, baseline suicide mortality rates (5 years preceding the earthquake) were 48.4 per 100,000 person-years in the disaster area and 46.1 in the control area, and suicide mortality rates during the 3-year period following the earthquake were 46.0 and 45.1, respectively. In women, baseline suicide mortality rates were 22.3 in the disaster area and 18.7 in the control area, and post-earthquake suicide mortality rates were 20.2 and 15.3, respectively. In consequence, the decrease in suicide mortality rate during the 3 years post-earthquake was significantly higher in the disaster area (2.5) than in the control area (1.0) (p = 0.0013) in men, whereas the decrease in suicide mortality rate was 2.1 in the disaster area and 3.0 in the control area (p = 0.1246) in women. We have concluded that the long-term mortality from suicide after the earthquake decreases in men and increases in women, suggesting that post-earthquake suicide mortality is sex-dependent. Post-earthquake suicide prevention strategies should more aggressively target women.

Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women.

AIM: To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC). METHODS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffin block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman SNP Genotyping Assays or Custom Taqman SNP Genotyping Assays. RESULTS: The non-ancestral T/T genotype of apolipoprotein B rs693 polymorphism was associated with a decreased risk of GBC (OR: 0.14, 95% CI: 0.03-0.63). The T/T genotype of cholesteryl ester transfer protein (CETP) rs708272 polymorphism was associated with an increased risk of GBC (OR: 5.04, 95% CI: 1.43-17.8). CONCLUSION: Genetic variants involved in gallstone formation such as the apolipoprotein B rs693 and CETP rs708272 polymorphisms may be related to the risk of developing GBC in Chilean women.

Rapid weight gain in early infancy is associated with adult body fat percentage in young women.

OBJECTIVES: Although rapid childhood weight gain has been suggested to be a risk factor for lifetime obesity and other chronic diseases, few studies have been conducted in Asian populations. The aim of this study was, therefore, to ascertain whether rapid childhood weight gain is associated with indices of obesity in adulthood and, if so, which period in early development provides the greatest predictive value of future obesity in young Japanese women. METHODS: A total of 86 female university students aged 18-21 years old participated in this study. Current height, weight, body fat percentage (BFP) as evaluated by bioelectrical impedance analysis, and BMI were measured. Body weight at birth, 3 and 6 months, and 1.5 and 3 years of age was obtained from the maternity record book (Boshi-techo), and body weight at 6 years was obtained from school health records. We assessed infant weight gain by the weight change Z-score. RESULTS: Current BFP was found to be significantly correlated with weight change between 0 and 3 months (r = 0.26, P = 0.034) and between 3 and 6 months of age (r = -0.28, P = 0.031). However, none of the physical activity indices correlated with BMI and BFP. CONCLUSIONS: Rapid weight gain in early infancy positively associates with BFP in young Japanese women.

Bone fracture in physically disabled children attending schools for handicapped children in Japan.

OBJECTIVE: Very few epidemiologic studies on bone fracture have been conducted in schools for handicapped children (Yogo schools). The aim of this study was to clarify the frequency and risk factors of bone fracture in physically disabled children in Japan. METHODS: We used a cross-sectional design to examine 525 physically disabled children in 38 Yogo schools in the Hokuriku-Koshinetsu District of Japan. The questionnaire surveyed information on participant sex, age, level of physical disability, and bone fracture history. Information on fractures was obtained, including number of fractures over participant lifetime, age when fractures occurred, location, and cause. One-year-period prevalence and lifetime prevalence were defined as the proportion of subjects with incident fractures in the previous year and with a history of fracture, respectively. RESULTS: Participant ages ranged from 6 to 15 years, and 66.3% had cerebral palsy (CP). The 1-year-period prevalence was 3.6% and lifetime fracture prevalence was 9.7%. The 1-year-period prevalence in the age groups of 6-9, 10-12, and 13-15 years was 2/184 (1.1%), 5/171 (2.9%), and 12/164 (7.3%), respectively (P for trend = 0.0031). There were no differences in period prevalence between sexes, and this was not associated with presence of CP. Multiple logistic regression analysis showed that age and presence of one joint contracture in the lower limbs or hip were independently associated with occurrence of bone fracture over participant lifetime. CONCLUSIONS: Physically disabled children are at high risk of bone fracture, and further risk factors should be determined.

Prevalence of attention-deficit/hyperactivity disorder (ADHD) symptoms in preschool children: discrepancy between parent and teacher evaluations.

OBJECTIVE: Clarifying the characteristics of attention-deficit/hyperactivity disorder (ADHD) symptoms in childhood is important for the prevention and management of this disorder. The purpose of this study was to determine the prevalence of ADHD symptoms in Japanese preschool children based on evaluations performed by parents or teachers. METHODS: A questionnaire survey was performed to evaluate the estimated prevalence of ADHD symptoms in preschool children in Niigata City, Japan. The first survey, conducted in 2003, involved an evaluation of ADHD symptoms by their school teachers. The second survey, conducted in 2006, involved an evaluation of the symptoms by parents. The teacher survey included 9,956 children, and the parent survey included 7,566 children. Parents and teachers assessed ADHD symptoms in children using a 14-item questionnaire based on DSM-III-R. Children with a score of 8 or higher were classified as having ADHD symptoms. RESULTS: The overall prevalence of ADHD symptoms was 2,349/7,566 (31.1%) in the parent survey and 431/9,956 (4.3%) in the teacher survey, with a prevalence ratio of 7.2 (95% CI: 6.5-7.9). Likelihood ratio test indicated that variables significantly associated with the presence of ADHD symptoms were gender, age, school type, interaction between gender and observer, and interaction between school type and observer (each with P < 0.0001). CONCLUSIONS: The large difference between the estimated prevalence of ADHD symptoms in Japanese preschool children from teacher and parent surveys suggests that compared to teachers, parents consider their children's symptoms much more serious. Thus, parental evaluation of ADHD symptoms using DSM criteria may be inappropriate for ADHD screening.

Low calcium intake is associated with increased bone resorption in postmenopausal Japanese women: Yokogoshi Study.

OBJECTIVE: Low Ca intake is common among Japanese women, but its effect on bone metabolism has not been fully elucidated. The aim of the present study was to determine the relationship between Ca intake and serum markers of bone turnover in postmenopausal Japanese women. DESIGN: A cross-sectional study. SETTING: A community setting. SUBJECTS: Subjects were 595 home-dwelling postmenopausal Japanese women. Ca intake was assessed by a validated FFQ. Serum type I collagen cross-linked N-telopeptides (NTX) and osteocalcin were measured as markers of bone turnover. The relationships between demographic characteristics, lifestyles, serum Ca, vitamin D and intact serum parathyroid hormone and bone turnover were also assessed. RESULTS: The average age of the subjects was 64.5 (sd 5.8) years and the mean Ca intake was 527 (sd 160) mg/d. Ca intake was significantly associated with serum NTX (P = 0.0104), but not with serum osteocalcin. Mean serum NTX concentration in the lowest quartile of Ca intake (<417 mg/d) was significantly higher than in the fourth, referent quartile. Among these Japanese postmenopausal women, very low Ca intake (less than approximately 400 mg/d) was associated with increased bone resorption but not bone formation. CONCLUSIONS: Increased bone resorption may be one mechanism by which this Ca-depleted population normalizes bone metabolism and prevents osteoporosis.

Microscopic hematuria is associated with low bone mineral density in aged women and men.

Little is known concerning renal or urological risk factors for osteoporosis. The aim of this study was to explore an association between urinalysis and bone mineral density (BMD) in 4,835 Japanese adults. Participants were 4,835 individuals (female 3,683; male 1,152) aged 50 years and over who received a health check-up between January 1995 and March 2006 in Japan. BMD of the distal radius and ulna of the non-dominant forearm was measured by the dual-energy X-ray absorptiometry (DXA) method using a DTX-200 Dexacare osteometer (Osteometer MediTech A/S, Rødovre, Denmark). Urine variables were protein, and red blood cells (RBCs) and white blood cells (WBCs) in urine sediment (categorized as <1, 1-4, 5-9, or >or=10 cells per high-power microscopic field). Average age was 58.9 years (SD 5.6) in women, and 60.5 years (SD 6.2) in men. Simple linear regression analysis showed that urinary RBCs were associated with BMD in women (beta = or-5.88 x 10(-3), R (2) = 0.004, p < 0.0001) and men (beta = or-1.34 x 10(-2), R (2) = 0.013, p = 0.0001). These associations held when possible confounders were adjusted (beta = or-2.05 x 10(-3), R (2) = 0.001, p = 0.0338 for women and beta =or -5.67 x 10(-3), R (2) = 0.006, p = 0.0163 for men). Microscopic hematuria is associated with forearm BMD in women and men aged 50 years and over. Further studies should be conducted to determine the mechanisms underlying this association.

Unhealthy maternal lifestyle leads to rapid infant weight gain: prevention of future chronic diseases.

Infants' rapid (catch-up) weight gain is associated with later obesity and chronic adult diseases. The aim of this study was to determine maternal and environmental factors related to rapid weight gain at one month and 18 months after full-term birth in Japan. Subjects were 1,524 infants and their mothers who visited the 18-month check-up in Niigata City between October 1, 2007 and September 30, 2008. An anonymous questionnaire elicited information on the infant's weight (at birth, 1 month, and 18 months), sex, feeding method, presence of food allergy, gestational age, and caregiver. Mother's information was height, pre-pregnancy weight, pregnancy weight gain, age at delivery, pregnancy toxicosis, number of daily meals during pregnancy, smoking and drinking habits. Some questionnaire items were obtained from a maternal and child health handbook. Independence of predictors for rapid weight gain (vs. slow or average weight gain), i.e. a score gain of 0.67 SD, during the first month and first 18 months was tested by multiple logistic regression analysis. In the first month, having a meal once or twice daily during pregnancy (P = 0.0016) and daily smoking in pre-pregnancy (P = 0.0175) were associated with rapid weight gain. In the first 18 months, use of daycare (P = 0.0083) and daily drinking in pre-pregnancy (P = 0.0130) were associated with rapid weight gain. We conclude that mother's pre-pregnancy smoking and drinking, dieting during pregnancy, and infant daycare attendance lead to rapid infant weight gain. Controlling these factors may prevent future chronic adult lifestyle-related diseases.

Effect of dietary intake on the levels of biliary unsaturated free Fatty acids having inhibitory activity on mutagens.

Unsaturated free fatty acids (FFAs), such as palmitoleic, oleic, linoleic, linolenic and arachidonic acids, have inhibitory actions on mutagenesis. These FFAs in bile may play a role in preventing cholecystopathy and their levels may be influenced by diet. However, the effects of dietary intake on biliary FFAs levels are not known. In order to examine possible associations between dietary habits and biliary FFAs levels, bile samples were collected from resected gallbladders of 114 Chilean female patients with gallstones, and FFAs were measured with an HPLC system. The long-term dietary intake of the patients was investigated through a semi-quantitative food frequency questionnaire. A high intake of vegetables was negatively correlated with the total FFA level (r = -0.264, P = 0.010). Positive correlations were found between fruit consumption and the lauric acid level (r = 0.200, P = 0.041), fish consumption and the levels of oleic (r = 0.370, P <0.0001), linolenic (r = 0.197, P = 0.038) and arachidonic (r = 0.200, P =0.035) acids, and consumption of foods fried in vegetable oil and the linoleic acid level (r = 0.269, P =0.004). Linoleic, linolenic, and arachidonic acids which may have an inhibitory effect on actions of unknown mutagens in bile appear to be increased by consumption of high levels of fish and fried foods.

Effect of genetic predisposition on the risk of gallbladder cancer in Hungary.

A CYP1A1 polymorphism has been associated with an increased risk for gallbladder cancer (GBC) in Japanese women. However, genetic risk factors for GBC in Hungary, where the population has a relatively high GBC incidence, has not been well studied. We therefore tested associations between CYP1A1 T3801C, CYP1A1 Ile462Val, GSTM1deletion, and TP53 Arg72Pro and GBC in Hungary. Genomic DNA was extracted from peripheral blood of 100 controls (52 men and 48 women) and from the tissue embedded in paraffin of 43 cases (6 men and 37 women). The case-control analysis was limited to females due to a small number of males. Of 37 female cases, 21 (56.8%) were diagnosed as adenocarcinoma, and the remaining 16 (43.2%) were classified as non-adenocarcinoma. The odds ratios (ORs) for the Ile/Val genotype and the Val allele were 8.9 (95% CI: 2.9-27.4) and 4.4 (95% CI: 1.7-11.1), respectively. The occurrence of the combined variant genotypes of CYP1A1 Ile462Val and GSTM1 (37.8% vs. 8.3%) or CYP1A1 Ile462Val and TP53 Arg72Pro (24.3% vs. 0%) was significantly higher in the cases than in the controls. The Ile/Val genotype was significantly associated with an increased risk of adenocarcinoma (OR 9.2; 95% CI: 2.6-32.6) and non-adenocarcinoma (OR 8.4; 95% CI: 2.2-32.4). Additionally, the Arg/Pro genotype increased risk of non-adenocarcinoma (OR 3.8; 95% CI: 1.2-12.8). The Val allele may contribute to the development of GBC not only in Japanese but also in Hungarian women. Our results provide a rationale for further studies of genetic variation on the risk of GBC in Hungary.

[Fracture-related medical cost of aged people in Niigata Prefecture, Japan: analysis of data from health insurance claims].

OBJECTIVES: The purpose of this study is to determine the fracture-related medical cost of aged people to reduce such cost. METHODS: Using health insurance claims, we obtained data on the number of aged people (> or =60 years of age) with fractures among members of the National Health Insurance Organization in Niigata Prefecture and their fracture-related medical cost, every May from 2003 to 2005. We analyzed these data and stratified them by sex, age (5-year age range), and hospitalization history. RESULTS: The average number of fractures per 100,000 people and the fracture-related medical cost per capita for women were 1,316+/-11 and 1,344+/-66 yen, respectively. These values were found to be more than twofold, those for men (604+/-11 and 556+/-33 yen, respectively). The number of fractures per 100,000 people and the fracture-related medical cost per capita increased with age. The fracture-related medical cost per hospitalization admission, however, did not increase with age. The amount of two-year increase in the fracture-related medical cost of hospitalization per capita was the largest in the > or =85 age group, and increased with the number of fractures. The fracture-related medical cost of people > or =60 years of age in Niigata prefecture was estimated to increase with age for women, but not for men. CONCLUSIONS: It is suggested that lowering the prevalence of fractures among very old women would lead to a decrease in the total fracture-related medical costs. Additional studies are needed to confirm the findings using nation wide data.