Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.

Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878) followed by replication (n = 1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6×10⁻¹4; LOC285735, rs271170, p = 2.7×10⁻¹²; OPG, rs7839059, p = 1.2×10⁻¹°; and ESR1/C6orf97, rs6909279, p = 1.1×10⁻9). The trabecular vBMD GWA meta-analysis (n = 2,500) followed by replication (n = 1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9×10⁻9). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60-0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, at least partly, via effects on cortical porosity, and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk.

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk.

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2 × 10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3 × 10(-12), and -0.16 SD per G allele, P = 1.2 × 10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3 × 10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9 × 10(-6) and rs2707466: OR = 1.22, P = 7.2 × 10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5 × 10(-13)

The Relationship between Dietary Habits and Work Engagement among Female Finnish Municipal Employees.

BACKGROUND: Work engagement reflects work-related well-being. It is positively associated with health, life satisfaction, work efficiency, income level, and occupational prospects. However, little is known about the relationship between work engagement and diet. METHODS: A cross-sectional study was conducted among female Finnish municipal employees (n = 630) in 2015. Work engagement was assessed using the Utrecht Work Engagement Index. The consumption of healthy and unhealthy food items was determined using a food frequency questionnaire. Sociodemographic factors, health behaviors, depressive and anxiety symptoms were assessed with self-administrated questionnaires. RESULTS: Work engagement had a positive relationship with the daily consumption of healthy food items. This association remained significant even after adjusting for age, education years, financial situation, and physical activity. The frequency of consuming unhealthy food items showed no relationship with work engagement. Anxiety and depressive symptoms decreased linearly with the greater consumption of healthy foods. CONCLUSION: Frequent consumption of healthy food items is associated with higher work engagement, irrespectively of the consumption of unhealthy nutrients. These results encourage health care professionals to recommend healthy food items instead of forbidding unhealthy food, as well as employers to support healthy dietary habits among employees.

Risk of Malnutrition and Insufficient Protein Intake among Older People Living at Home: Baseline Findings of the Power Meals Study.

This study aimed to investigate the nutritional status, nutrient intake and associated factors among older home care clients, caregivers and care recipients (≥65 years) living at home. There were a total of 78 participants, with a mean age of 78 ± 7.4 years. Nutritional status was assessed with the Mini Nutritional Assessment (MNA), nutrient intake with a three-day food record, sarcopenia with a Simple Questionnaire to Rapidly Diagnose Sarcopenia (SARC) and depression with The Geriatric Depression Scale (GDS-15). Almost one-third (32.1%) were at risk of malnutrition and 2.6% suffered from malnutrition. Impaired nutritional status was associated with depressive symptoms (ß = -0.277, p = 0.015) and risk of sarcopenia (SARC points) (ß = -0.401, p = 0.001). Mean protein intake was 0.9 ± 0.3 g/adjusted body weight/day. Intakes of protein and multiple vitamins and minerals were lower than recommended. In conclusion, a third of older people living at home were at risk of malnutrition or malnourished. Multiple physical, psychological and social factors in older adults were associated with nutritional status and protein intake.

Healthy and Unhealthy Food Consumption in Relation to Quality of Life among Finnish Female Municipal Employees: A Cross-Sectional Study.

Aspects of good quality of life (QoL) have been found to motivate people to make lifestyle changes. There is also evidence that certain dietary patterns are associated with QoL. The aim of this work was to examine whether consumption frequencies of healthy and unhealthy food items are associated with QoL in female employees. A cross-sectional study was conducted among 631 Finnish female employees (mean age 49 years, SD = 10) from 10 municipal work units in 2015. Information about the participants was collected by physical examination, laboratory tests, self-administered questionnaires, including the Food Frequency Questionnaire (FFQ), and from medical history. QoL was assessed with the EUROHIS-Quality of Life 8-item index. A significant positive association was seen between consumption frequency of healthy foods and the EUROHIS-QOL mean score (p = 0.002). The association was small but comprehensive, also involving most dimensions of QoL. The consumption frequency of unhealthy foods was not associated with QoL. These findings are relevant when designing diet counselling, since QoL is an outcome that has been found to motivate people to change their health habits. Recommending abundant use of healthy foods could be a simple and convenient way of diet counselling at many health care appointments, where time consuming approaches are difficult to conduct.

Gene set analysis of transcriptomics data identifies new biological processes associated with early markers of atherosclerosis but not with those of osteoporosis: Atherosclerosis-osteoporosis co/multimorbidity study in the Young Finns Study.

AIM: We aimed at identifying the shared biological processes underlying atherosclerosis-osteoporosis co/multimorbidity. METHODS: We performed gene set analysis (GSA) of whole-blood transcriptomic data to identify biological processes shared by the early markers of these two diseases. Early markers of diseases, carotid intima-media thickness (CIMT) for atherosclerosis and trabecular bone mineral density (BMD) from distal radius and tibia for osteoporosis, were used to categorize the study participants into cases and controls. Participants with high CIMT (>90th percentile) were defined as cases for subclinical atherosclerosis. Study population-based T-scores for BMD were calculated and T-score ≤ -1 was used for the definition of low BMD cases i.e., early indicator of osteoporosis. RESULTS: We did not identify any gene sets jointly associated with early markers of atherosclerosis and osteoporosis. We identified three novel and replicated 234 gene sets significantly associated with high CIMT with false discovery rate (FDR) ≤ 0.01. Only two genes, both related to the immune system, were identified to be associated with high CIMT by traditional differential gene expression analysis. However, none of the studied gene sets or individual genes were significantly associated with tibial or radial BMD. The three novel CIMT associated gene sets contained genes involved in copper homeostasis, neural crest cell migration and nicotinate and nicotinamide metabolism. The 234 replicated gene sets in this study are related to the immune system, hypoxia and apoptosis, consistent with the existing literature on atherosclerosis. CONCLUSIONS: This study identified novel biological processes associated with high CIMT but not with reduced BMD.

Lactase gene c/t(-13910) polymorphism, calcium intake, and pQCT bone traits in Finnish adults.

Genetic lactase nonpersistence may influence calcium intake and thereby bone health. We investigated in the Cardiovascular Risk in Young Finn Study whether young adults aged 31-46 years with the C/C(-13910) genotype are more susceptible to reduced bone phenotypes, low-energy fractures, and low calcium intake than subjects with other lactase genotypes. We also analyzed the gene-environment interactions on bone with calcium intake and physical activity. Peripheral quantitative computed tomography bone traits were measured from the distal and shaft sites of the radius and tibia. The total number of those subjects whose nondominant forearm was measured and the lactase genotype was defined was 1551. Information on diet, lifestyle factors, and fractures was collected with questionnaires. The mean intake of calcium was the lowest in men with the C/C(-13910) genotype (P = 0.001). Men with the T/T(-13910) genotype had ~3% higher trabecular density at the distal radius and distal tibia compared to other lactase genotypes (P = 0.03 and 0.02, respectively). In women, we found no evidence of the gene effect at the radius and tibia. No major interactions of the C/T(-13910) polymorphism with calcium intake or physical activity on bone phenotypes were found in either sex. In conclusion, the C/T(-13910) polymorphism was associated with trabecular density at the distal radius and tibia in men. These differences may be due to the differences in calcium intake between the lactase genotypes.

The Association between Healthy Diet and Burnout Symptoms among Finnish Municipal Employees.

BACKGROUND: Burnout is an undesirable mental condition, which may have a negative impact on individuals' health and work ability. This study aimed to evaluate the relationship between diet and burnout symptoms among female public sector employees. METHODS: A cross-sectional study was conducted in 2015 among 630 female employees from 10 municipal work units of the city of Pori, Finland. Burnout symptoms were assessed with the Bergen Burnout Indicator (BBI). The consumption of food items was determined using the food frequency questionnaire (FFQ). The main food groups were categorized into healthy and unhealthy foods based on the Nordic Nutrition Recommendations for a healthy and balanced diet. RESULTS: In multivariate linear regression analysis, consumption of healthy food items had an inverse relationship with the severity of burnout symptoms independently of age, education years, physical activity, and depressive symptoms. De-tailed analysis revealed that subjects with lower BBI score consumed more often low-fat dairy produce, vegetables, fruit and berries, vegetable food, and white meat. CONCLUSIONS: Frequent consumption of healthy food items is associated with low level of burnout symptoms. Our results emphasize the importance of diverse and balanced healthy diet to promote work well-being.

Effects of Home-Delivered Meals on Older People's Protein Intake, Physical Performance, and Health-Related Quality of Life: The Power Meals Randomized Controlled Trial.

This trial examined the effectiveness of an 8-week home meal service on protein and other nutrient intake, physical performance (PP) and health related quality of life (HRQoL) among older people living at home (≥65 years; home care clients, caregivers and care recipients). Participants were randomized into three groups; (1) protein-rich meal, snack, and bread (INT1), (2) regular meal (INT2) and (3) control group. Nutrient intake was assessed with 3-day food diaries, PP with Short Physical Performance Battery (SBBP) and HRQoL with 15 dimensional Health-related quality of life instrument. Total of 67 (59.7% women, mean age 78.2 years) participants (n = 22 INT1, n = 24 INT2, n = 21 CG) completed the trial. At baseline, mean protein intake was 0.92 (SD 0.32) g/kg adjusted body weight (aBW)/d. At 8 weeks, protein-rich home meal service in INT1 increased protein intake (+ 0.11 (95%CI -0.01 to 0.21) g/kg aBW/d, 9.4 (95%CI 1.0 to 17.8) g/d) compared to other groups. It also increased calcium intake (+169.9 (95%CI 26 to 314) mg/d) and improved results in Sit-to-Stand Test (-4.8 (95%CI -6.8 to -2.7) sec) in INT1 compared to CG. Both home meal services increased saturated fat intake (INT1; 4.6 (95%CI 1.0-8.2) g/d, INT2;7.8 (95%CI 1.9 to 13.7)g/d) and decreased salt intake (INT1;-2330.9 (95%CI -2998 to -1664) mg/d, INT2; -2371.9 (95%CI -3399 to -1345) mg/d) compared to CG. There was no effect on overall HRQoL.

Uncovering the shared lipidomic markers of subclinical osteoporosis-atherosclerosis comorbidity: The Young Finns Study.

BACKGROUND: Osteoporosis and atherosclerosis are complex multifactorial diseases sharing common risk factors and pathophysiological mechanisms suggesting that these are comorbidities. Omics studies identifying joint molecular markers associated with these diseases are sparse. SUBJECTS AND METHODS: Using liquid chromatography-tandem mass spectrometry, we quantified 437 molecular lipid species from the Young Finns Study cohort (aged 30-45 years and 57% women) and performed lipidome-wide multivariate analysis of variance (MANOVA) with early markers for both diseases. Carotid intima-media thickness for atherosclerosis measured with ultrasound and bone mineral density from distal radius and tibia for osteoporosis measured with peripheral quantitative computed tomography were used as early markers of the diseases. RESULTS: MANOVA adjusted with age, sex and body mass index, identified eight statistically significant (adjusted p-value (padj) < 0.05) and 15 suggestively significant (padj < 0.25) molecular lipid species associated with the studied markers. Similar analysis adjusted additionally for smoking habit, physical activity and alcohol consumption identified four significant and six suggestively significant molecular lipid species. These most significant lipid classes/species jointly associated with the studied markers were glycerolipid/TAG(18:0/18:0/18:1), glycerophospholipid/PC(40:3), sphingolipid/Gb3(d18:1/22:0), and sphingolipid/Gb3(d18:1/24:0). CONCLUSION: Our results support the osteoporosis-atherosclerosis comorbidity hypothesis and present potential new joint lipid biomarkers for these diseases.

Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis in the Young Finns Study.

We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj) < 0.05) and another two had suggestively significant (p.adj < 0.25) joint association with the two diseases after adjusting for age, sex, body mass index, smoking habit, alcohol consumption, and physical activity. The three most significant member genes from the significant modules were NOSIP, GXYLT2, and TRIM63 (p.adj ≤ 0.18). Genes in the modules were enriched with biological processes that have separately been found to be involved in either bone metabolism or atherosclerosis. The gene modules and their most significant member genes identified in this study support the osteoporosis-atherosclerosis comorbidity hypothesis and can provide new joint biomarkers for both diseases and their dual prevention.

Low calcium:phosphorus ratio in habitual diets affects serum parathyroid hormone concentration and calcium metabolism in healthy women with adequate calcium intake.

Excessive dietary P intake alone can be deleterious to bone through increased parathyroid hormone (PTH) secretion, but adverse effects on bone increase when dietary Ca intake is low. In many countries, P intake is abundant, whereas Ca intake fails to meet recommendations; an optimal dietary Ca:P ratio is therefore difficult to achieve. Our objective was to investigate how habitual dietary Ca:P ratio affects serum PTH (S-PTH) concentration and other Ca metabolism markers in a population with generally adequate Ca intake. In this cross-sectional analysis of 147 healthy women aged 31-43 years, fasting blood samples and three separate 24-h urinary samples were collected. Participants kept a 4-d food record and were divided into quartiles according to their dietary Ca:P ratios. The 1st quartile with Ca:P molar ratio < or = 0.50 differed significantly from the 2nd (Ca:P molar ratio 0.51-0.57), 3rd (Ca:P molar ratio 0.58-0.64) and 4th (Ca:P molar ratio > or = 0.65) quartiles by interfering with Ca metabolism. In the 1st quartile, mean S-PTH concentration (P = 0.021) and mean urinary Ca (U-Ca) excretion were higher (P = 0.051) than in all other quartiles. These findings suggest that in habitual diets low Ca:P ratios may interfere with homoeostasis of Ca metabolism and increase bone resorption, as indicated by higher S-PTH and U-Ca levels. Because low habitual dietary Ca:P ratios are common in Western diets, more attention should be focused on decreasing excessively high dietary P intake and increasing Ca intake to the recommended level.

Lipidomic architecture shared by subclinical markers of osteoporosis and atherosclerosis: The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Studies have shown that osteoporosis and atherosclerosis are comorbid conditions sharing common risk factors and pathophysiological mechanisms. Understanding these is crucial in order to develop shared methods for risk stratification, prevention, diagnosis and treatment. The aim of this study was to apply a system-level bioinformatics approach to lipidome-wide data in order to pinpoint the lipidomic architecture jointly associated with surrogate markers of these complex comorbid diseases. SUBJECTS AND METHODS: The study was based on the Cardiovascular Risk in Young Finns Study cohort from the 2007 follow-up (n = 1494, aged 30-45 years, women: 57%). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyse the serum lipidome, involving 437 molecular lipid species. The subclinical osteoporotic markers included indices of bone mineral density and content, measured using peripheral quantitative computer tomography from the distal and shaft sites of both the tibia and the radius. The subclinical atherosclerotic markers included carotid and bulbus intima media thickness measured with high-resolution ultrasound. Weighted co-expression network analysis was performed to identify networks of densely interconnected lipid species (i.e. lipid modules) associated with subclinical markers of both osteoporosis and atherosclerosis. The levels of lipid species (lipid profiles) of each of the lipid modules were summarized by the first principal component termed as module eigenlipid. Then, Pearson's correlation (r) was calculated between the module eigenlipids and the markers. Lipid modules that were significantly and jointly correlated with subclinical markers of both osteoporosis and atherosclerosis were considered to be related to the comorbidities. The hypothesis that the eigenlipids and profiles of the constituent lipid species in the modules have joint effects on the markers was tested with multivariate analysis of variance (MANOVA). RESULTS: Among twelve studied molecular lipid modules, we identified one module with 105 lipid species significantly and jointly associated with both subclinical markers of both osteoporosis (r = 0.24, p-value = 2 × 10-20) and atherosclerosis (r = 0.16, p-value = 2 × 10-10). The majority of the lipid species in this module belonged to the glycerolipid (n = 60), glycerophospholipid (n = 13) and sphingolipid (n = 29) classes. The module was also enriched with ceramides (n = 20), confirming their significance in cardiovascular outcomes and suggesting their joint role in the comorbidities. The top three of the 37 statistically significant (adjusted p-value < 0.05) lipid species jointly associated with subclinical markers of both osteoporosis and atherosclerosis within the module were all triacylglycerols (TAGs) - TAG(18:0/18:0/18:1) with an adjusted p-value of 8.6 × 10-8, TAG(18:0/18:1/18:1) with an adjusted p-value of 3.7 × 10-6, and TAG(16:0/18:0/18:1) with an adjusted p-value of 8.5 × 10-6. CONCLUSION: This study identified a novel lipid module associated with both surrogate markers of both subclinical osteoporosis and subclinical atherosclerosis. Alterations in the metabolism of the identified lipid module and, more specifically, the TAG related molecular lipids within the module may provide potential new biomarkers for testing the comorbidities, opening avenues for the emergence of dual-purpose prevention measures.

Genetic lactase non-persistence, consumption of milk products and intakes of milk nutrients in Finns from childhood to young adulthood.

Previous evidence suggests that the lactase gene C/T- 13910 polymorphism (rs4988235) is associated with avoidance of milk products and lower Ca intake. We examined whether the consumption of milk and milk products and the intakes of milk nutrients differ between the lactase genotypes from childhood to young adulthood. Subjects belong to the Cardiovascular Risk in Young Finns Study where the first cross-sectional surveys were conducted in 1980 (n 3596), with follow-up studies in 1983, 1986, 1989, 1992 and 2001 (n 2620). The same dietary questionnaire was used throughout the follow-up to collect data on habitual consumption of milk and milk products in all subjects, and daily nutrient intakes were assessed with 48 h dietary recalls in 50 % of the subjects. Subjects with the lactase non-persistence (C/C- 13910) genotype consumed less milk since childhood, but the consumption of other milk products did not differ between the genotypes. In adult females, the lactose content of milk products consumed was lower (P = 0.003), and in both sexes low-lactose and milk-free diets were more common in the C/C- 13910 genotype than in the other genotypes. Inadequate Ca intake was most common in females with the C/C- 13910 genotype as early as in childhood (15-63 %), but in males only in adulthood (24 %). In adult females, preference for low-lactose milk and milk products equalised the differences in Ca intake between the genotypes. Thus, in those with the C/C- 13910 genotype, preference for low-lactose milk and milk products may decrease the risk for inadequate Ca intake.

Long-term dietary patterns and carotid artery intima media thickness: the Cardiovascular Risk in Young Finns Study.

A whole-diet approach has proven useful for characterising dietary exposure in cardiovascular epidemiology research. In our previous analyses, we found dietary patterns to be significant determinants of CVD risk factor levels among the Cardiovascular Risk in Young Finns cohort. We investigated the associations of major dietary patterns with carotid intima media thickness (IMT), a subclinical predictor of CVD, in healthy adults. The Young Finns Study is an ongoing, prospective cohort study with a 21-year follow-up to date. The subjects were children and adolescents at baseline in 1980 (aged 3-18 years), and all had reached adulthood by the latest follow-up in 2001 (aged 24-39 years). Complete dietary data from the years 1980, 1986 and 2001 and outcome data from the year 2001 were obtained from 785 subjects. The long-term average pattern score for a traditional dietary pattern (characterised by high consumption of rye, potatoes, butter, sausages, milk and coffee) was associated with IMT especially among subjects with a low score for the health-conscious dietary pattern (characterised by high consumption of vegetables, legumes and nuts, rye, tea, cheese and other dairy products). In multivariable regression analyses using long-term pattern scores as predictors, the traditional dietary pattern was independently associated with IMT in men (P < 0.01), but not in women (P = 0.66). Long-term adherence to traditional food choices seems to increase the risk of developing subclinical atherosclerosis among Finnish men.

Habitual high phosphorus intakes and foods with phosphate additives negatively affect serum parathyroid hormone concentration: a cross-sectional study on healthy premenopausal women.

OBJECTIVE: Foods can contain natural phosphorus (NP) and phosphate-containing food additives (AP). The main objective of the present study was to investigate whether NP and AP of habitual diets differ in their effects on markers of Ca metabolism. We also investigated the impact of total habitual dietary P intake on markers of Ca metabolism. DESIGN: Cross-sectional study. Fasting blood samples were collected and participants kept a 4 d food record, from which dietary intake of total P and the consumption of NP (milk and cheese, excluding processed cheese) and AP (processed cheese) sources were calculated. Participants were divided into groups according to their NP- and AP-containing food consumption and into quartiles according to their total P intake. SETTING: Southern Finland. SUBJECTS: One hundred and forty-seven healthy premenopausal women aged 31-43 years. RESULTS: Relative to the lowest total dietary P quartile, mean serum parathyroid hormone (S-PTH) concentration was higher (P = 0.048, analysis of covariance (ANCOVA)) and the mean serum ionized Ca concentration lower (P = 0.016, ANCOVA) in the highest P intake quartile. Mean S-PTH concentrations were higher among participants who consumed processed cheese (P = 0.027, ANCOVA) and less milk and other cheese than processed cheese (P = 0.030, ANCOVA). CONCLUSIONS: High total habitual dietary P intake affected S-PTH unfavourably. Furthermore, phosphate additives may have more harmful effects on bone than other P sources, as indicated by higher mean S-PTH concentration among participants who consumed AP-containing foods. Because of the high dietary P intake and current upward trend in consumption of processed foods in Western countries, these findings may have important public health implications.

Childhood Exposure to Passive Smoking and Bone Health in Adulthood: The Cardiovascular Risk in Young Finns Study.

CONTEXT: Passive smoke exposure has been linked to the risk of osteoporosis in adults. OBJECTIVE: We examined the independent effects of childhood passive smoke exposure on adult bone health. DESIGN/SETTING: Longitudinal, the Cardiovascular Risk in Young Finns Study. PARTICIPANTS: The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires. RESULTS: Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (ß± SE, -0.064 ± 0.023 per smoking parent; P = 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (ß± SE, -0.097 ± 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (ß± SE, -0.206 ± 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels (<3 ng/mL) (ß± SE, -0.192 ± 0.072; P = 0.008). CONCLUSIONS AND RELEVANCE: Children of parents who smoke have evidence of impaired bone health in adulthood.

Adult-type hypolactasia is not a predisposing factor for the early functional and structural changes of atherosclerosis: the Cardiovascular Risk in Young Finns Study.

Individuals suffering from ATH (adult-type hypolactasia), defined by the LCT (gene encoding lactase-phlorizin hydrolase) C/C(-13910) genotype (rs4988235), use less milk and dairy products and may have higher plasma HDL (high-density lipoprotein) and lower triacylglycerol (triglyceride) concentrations than their counterparts without ATH. To investigate the effects of ATH status on the early markers of atherosclerosis, we examined its association with CIMT (carotid intima-media thickness), CAC (carotid artery compliance) and brachial artery FMD (flow-mediated dilation) in a young population-based cohort of otherwise healthy individuals. As part of the Cardiovascular Risk in Young Finns Study, we performed CIMT, CAC and FMD analyses, LCT C/T(-13910) genotyping and risk factor determination in 2109 young subjects 24-39 years of age (45% males) at the time of the examination. The consumption of both milk and dairy products was lowest and the consumption of alcohol highest in subjects with the C/C(-13910) genotype (P<0.001 for all) in comparison with subjects without ATH (TT+CT). In multivariate analysis, no significant association between ATH status and CIMT, CAC or brachial artery FMD was found after adjustment for the use of alcohol, dairy products and all other major risk factors of coronary artery disease. In otherwise similar statistical analysis, the results remained non-significant when females and males were analysed in their own groups. In conclusion, the finding does not support the involvement of ATH in the pathogenesis of early atherosclerosis.

Vitamin D deficiency and low bone status in adult female garment factory workers in Bangladesh.

The manufacture of garments is the main industry in Bangladesh and employs 1.6 million female workers. Due to the indoor lifestyle and low dietary intake of calcium, we hypothesised that they are at risk of low vitamin D and bone mineral status. Two hundred female garment workers (aged 18-36 years) were randomly selected. Serum 25-hydroxyvitamin D (S-25OHD), serum intact parathyroid hormone (S-iPTH), serum calcium (S-Ca), serum phosphate (S-P) concentration and serum alkaline phosphatase activity (S-ALP) were measured from fasting samples. Bone indexes of hip and spine were measured by dual-energy X-ray absorptiometry. The mean S-25OHD (36.7 nmol/l) was low compared to that recommended for vitamin D sufficiency. About 16% of the subjects were found to be vitamin D-deficient (S-25OHD 21 ng/l) was associated with progressive reduction in bone mineral density at the femoral neck and lumbar spine. According to the WHO criteria, the mean T-score of the femoral neck and lumbar spine of the subjects were within osteopenic range. We observed that subjects with a bone mineral density T-score < -2.5 had a trend of lower values of BMI, waist-hip circumference, mid-upper-arm circumference, S-25OHD and higher S-iPTH and S-ALP. The high prevalence of hypovitaminosis D and low bone mineral density among these subjects are indicative of higher risk for osteomalacia or osteoporosis and fracture.

Higher step count is associated with greater bone mass and strength in women but not in men.

In this cross-sectional study, peripheral bone traits were examined relative to total daily steps measured with pedometer. Higher number of steps was associated with greater bone values at the calcaneus and tibia in women, but not in men. In women, dose-dependent associations at the radius were congruent with the weight-bearing bones. INTRODUCTION: Habitual physical activity measured as daily steps may contribute to bone density and strength at the calcaneus and other weight-bearing bones. METHODS: Subgroups of 705-837 women and 480-615 men aged 31-46 years from the Cardiovascular Risk in Young Finns Study participated in the present study. Participants were instructed to use pedometer for 1 week, and the total daily steps, divided into tertiles, were evaluated relative to quantitative ultrasound-measured bone traits at the calcaneus and peripheral quantitative computed tomography-measured bone traits at the tibia and radius. Analysis of covariance was used to examine the between-group differences. RESULTS: In women, significant dose-dependent between-group differences were found in the weight-bearing bones and in non-weight-bearing radius. The differences in broadband ultrasound attenuation and speed of sound at the calcaneus were 3.8 and 0.5% greater in women within the highest tertile of daily steps compared to the lowest tertile (p values for trend ≤ 0.04). In tibia, women in the highest tertile (> 8765 steps/day) had on average 1-5.4% greater bone cross-sectional area, bone mineral content (BMC), trabecular density, and bone strength index at the distal site and 1.6-2.7% greater bone areas, BMC and strength strain index (SSI) at the shaft compared to women with less daily steps (p values for trend ≤ 0.02). Similarly, in radius, BMC and BSI at the distal site, and bone cross-sectional areas, BMC and SSI at the shaft were 1.7-3.4% greater in women within the highest tertile of daily steps compared to their peers (p values for trend ≤ 0.04). In men, the differences in calcaneal, tibial, and radial bone traits were mainly non-significant between the tertiles of daily steps. CONCLUSION: Observed significant positive associations between daily steps and various bone traits at the calcaneus, tibia, and radius in women suggest that habitual physical activity may benefit skeletal health in adulthood.