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1.
J Nutr Gerontol Geriatr ; 41(4): 257-269, 2022.
Article in English | MEDLINE | ID: mdl-36459463

ABSTRACT

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.


Subject(s)
Malnutrition , Sarcopenia , Humans , Aged , Aged, 80 and over , Sarcopenia/epidemiology , Malnutrition/epidemiology , Malnutrition/diagnosis , Nutritional Status , Nutrition Assessment , Meals , Geriatric Assessment
2.
Atherosclerosis ; 361: 1-9, 2022 11.
Article in English | MEDLINE | ID: mdl-36252457

ABSTRACT

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.


Subject(s)
Atherosclerosis , Biological Phenomena , Osteoporosis , Humans , Carotid Intima-Media Thickness , Multimorbidity , Transcriptome , Finland , Cross-Sectional Studies , Osteoporosis/epidemiology , Osteoporosis/genetics , Osteoporosis/complications , Atherosclerosis/diagnosis , Atherosclerosis/epidemiology , Atherosclerosis/genetics , Biomarkers , Risk Factors
3.
Nutrients ; 14(17)2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36079887

ABSTRACT

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.


Subject(s)
Life Style , Quality of Life , Cross-Sectional Studies , Diet , Female , Finland , Humans , Middle Aged , Surveys and Questionnaires
4.
Nutrients ; 14(6)2022 Mar 17.
Article in English | MEDLINE | ID: mdl-35334924

ABSTRACT

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.


Subject(s)
Feeding Behavior , Work Engagement , Cross-Sectional Studies , Diet , Female , Finland , Humans
5.
Nutrients ; 13(7)2021 Jul 13.
Article in English | MEDLINE | ID: mdl-34371901

ABSTRACT

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.


Subject(s)
Burnout, Professional/prevention & control , Diet, Healthy , Occupational Health , Public Sector , Risk Reduction Behavior , Women's Health , Adult , Burnout, Professional/diagnosis , Burnout, Professional/epidemiology , Cross-Sectional Studies , Female , Finland/epidemiology , Humans , Middle Aged , Nutritional Status , Nutritive Value , Protective Factors , Recommended Dietary Allowances , Risk Assessment , Risk Factors , Sex Factors
6.
Bone ; 151: 116030, 2021 10.
Article in English | MEDLINE | ID: mdl-34098163

ABSTRACT

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.


Subject(s)
Atherosclerosis , Osteoporosis , Biomarkers , Carotid Intima-Media Thickness , Comorbidity , Female , Finland/epidemiology , Humans , Lipidomics , Male , Osteoporosis/epidemiology , Risk Factors
7.
Sci Rep ; 11(1): 7111, 2021 03 29.
Article in English | MEDLINE | ID: mdl-33782480

ABSTRACT

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.


Subject(s)
Atherosclerosis/genetics , Gene Expression , Genome, Human , Osteoporosis/genetics , Adult , Biomarkers , Bone Density , Cohort Studies , Female , Finland , Humans , Life Style , Male , Middle Aged , Osteoporosis/diagnostic imaging , Reproducibility of Results
8.
J Nutr Gerontol Geriatr ; 40(2-3): 125-149, 2021.
Article in English | MEDLINE | ID: mdl-33684023

ABSTRACT

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.


Subject(s)
Dietary Proteins/metabolism , Food Services , Malnutrition/prevention & control , Meals/physiology , Aged , Eating/physiology , Energy Intake/physiology , Female , Food Services/organization & administration , Food Services/statistics & numerical data , Home Care Services/organization & administration , Home Care Services/statistics & numerical data , Humans , Male , Nutritional Status , Outcome and Process Assessment, Health Care , Physical Functional Performance
9.
Bone ; 131: 115160, 2020 02.
Article in English | MEDLINE | ID: mdl-31759205

ABSTRACT

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.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Osteoporosis , Atherosclerosis/diagnostic imaging , Biomarkers , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/epidemiology , Carotid Intima-Media Thickness , Chromatography, Liquid , Female , Finland , Heart Disease Risk Factors , Humans , Lipidomics , Osteoporosis/diagnostic imaging , Risk Factors , Tandem Mass Spectrometry
10.
J Clin Endocrinol Metab ; 104(6): 2403-2411, 2019 06 01.
Article in English | MEDLINE | ID: mdl-30715377

ABSTRACT

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.


Subject(s)
Bone Density , Cardiovascular Diseases/etiology , Tobacco Smoke Pollution/adverse effects , Adolescent , Adult , Child , Child, Preschool , Cotinine/blood , Female , Humans , Male , Middle Aged , Parents , Risk
11.
Arch Osteoporos ; 13(1): 20, 2018 03 06.
Article in English | MEDLINE | ID: mdl-29511893

ABSTRACT

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.


Subject(s)
Calcaneus/diagnostic imaging , Motor Activity/physiology , Radius/diagnostic imaging , Tibia/diagnostic imaging , Weight-Bearing/physiology , Adult , Bone Density , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Sex Factors , Tomography, X-Ray Computed , Ultrasonography
12.
J Bone Miner Res ; 29(4): 1015-24, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24014423

ABSTRACT

We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum ß-C-telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMDC ). CTX and mid-tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (ß=0.19 [0.13, 0.24]) (coefficient=SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMDC (ß=-0.46 [-0.52,-0.40]) and cortical thickness [ß=-0.11 (-0.18, -0.03)]. CTX was positively related to bone strength as reflected by the strength-strain index (SSI) (ß=0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single-nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p<0.05 cut-off) (n=2379). Subsequently, we performed a meta-analysis of associations between these SNPs and PC in ALSPAC (n=3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n=938), and the Young Finns Study (YFS) (n=1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (p<0.05 cut-off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion.


Subject(s)
Bone Resorption , Collagen Type I/genetics , Genetic Markers , Periosteum/anatomy & histology , RANK Ligand/metabolism , Tomography, X-Ray Computed/methods , Adolescent , Collagen Type I/chemistry , Cross-Sectional Studies , Female , Humans , Male
13.
PLoS Genet ; 9(2): e1003247, 2013.
Article in English | MEDLINE | ID: mdl-23437003

ABSTRACT

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.


Subject(s)
Bone Density/genetics , Bone and Bones , Genome-Wide Association Study , Intercellular Signaling Peptides and Proteins , RANK Ligand/genetics , Absorptiometry, Photon , Alleles , Bone and Bones/diagnostic imaging , Bone and Bones/ultrastructure , Cytokines , Fractures, Bone/diagnostic imaging , Fractures, Bone/genetics , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Osteoblasts/metabolism , Osteoporosis/diagnostic imaging , Osteoporosis/genetics , Sweden , Tomography, X-Ray Computed
14.
PLoS Genet ; 8(7): e1002745, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22792071

ABSTRACT

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)

Subject(s)
Bone Density/genetics , Fractures, Bone/genetics , Genome-Wide Association Study , Osteoporosis/genetics , Wnt Proteins/genetics , Adolescent , Adult , Animals , Bone Density/physiology , Bone and Bones/physiology , Child , Child, Preschool , Female , Femur , Forearm , Humans , Male , Mice , Middle Aged , Polymorphism, Single Nucleotide , Risk Factors
15.
Nat Genet ; 44(5): 491-501, 2012 Apr 15.
Article in English | MEDLINE | ID: mdl-22504420

ABSTRACT

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.


Subject(s)
Bone Density/genetics , Fractures, Bone/genetics , Osteoporosis/genetics , Polymorphism, Single Nucleotide/genetics , Quantitative Trait Loci , Computational Biology , Extracellular Matrix Proteins/genetics , Female , Femur Neck/physiopathology , Gene Expression Profiling , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Glycoproteins/genetics , Humans , Intercellular Signaling Peptides and Proteins/genetics , Low Density Lipoprotein Receptor-Related Protein-5/genetics , Lumbar Vertebrae/physiopathology , Male , Mitochondrial Membrane Transport Proteins/genetics , Phosphoproteins/genetics , Risk Factors , Spectrin/genetics , White People
16.
Bone ; 48(5): 1058-65, 2011 May 01.
Article in English | MEDLINE | ID: mdl-21266206

ABSTRACT

Association of apolipoprotein E (APOE) ε4 allele with peripheral quantitative computed tomography (pQCT) bone traits at the distal and shaft sites of the radius and tibia was evaluated in the Young Finns Cohort (n=1777). We also analyzed the interactions of the APOE promoter polymorphisms (-219G/T rs405509 and +113G/C rs440446) and bone traits within the APOE ε3/ε3 genotype (n=1025 and n=1013, respectively), and investigated the gene-environment interactions on bone traits with longitudinal saturated fatty acids (SAFA) intake. Differences between the ε4 allele carriers and noncarriers were modest and mostly nonsignificant. Within the APOE promoter -219G/T polymorphism, cortical strength index (CSI) and compressive bone strength index (BSI) at the distal radius (linear, P=0.003 and P=0.05, respectively) and tibia (linear, P=0.01 and P=0.03, respectively), and CSI at the tibial shaft (linear, P=0.04) decreased towards the -219T/T genotype in women. In men, total cross-sectional areas at the radial site and stress-strain index (SSI) at the radial shaft (linear, P=0.03 and P=0.04 and P=0.05, respectively) increased, and conversely cortical bone density and CSI at the radial shaft (linear, P=0.005 and P=0.05, respectively) and CSI at the tibial shaft (linear, P=0.03) decreased towards the -219T/T genotype. In the highest SAFA tertile, women with the -219T/T genotype had the smallest total area and SSI at the radial shaft (P=0.01 and P=0.02, respectively). Subjects with the APOE +113C/C genotype shared similar bone traits as subjects with the APOE -219T/T genotype. In conclusion, APOE genotypes -219T/T and +113C/C could be genetic markers for cortical bone strength. Furthermore, high longitudinal SAFA intake seems to be more detrimental to bone in women with the -219T/T and +133C/C genotypes than others.


Subject(s)
Apolipoproteins E/genetics , Bone and Bones/anatomy & histology , Cardiovascular Diseases/genetics , Dietary Fats/pharmacology , Fatty Acids/pharmacology , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic , Adolescent , Adult , Bone and Bones/diagnostic imaging , Cardiovascular Diseases/blood , Child , Child, Preschool , Cholesterol/blood , Feeding Behavior/drug effects , Female , Finland , Gene Frequency/genetics , Heterozygote , Humans , Male , Middle Aged , Radiography , Radius/anatomy & histology , Radius/diagnostic imaging , Risk Factors , Tibia/anatomy & histology , Tibia/diagnostic imaging
17.
Calcif Tissue Int ; 88(2): 153-61, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21136048

ABSTRACT

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.


Subject(s)
Bone Density/genetics , Calcium, Dietary/metabolism , Lactase/genetics , Polymorphism, Genetic , Adult , Cardiovascular Diseases/genetics , Cohort Studies , Female , Finland , Fractures, Bone/diagnostic imaging , Fractures, Bone/genetics , Genotype , Humans , Lactose Intolerance/genetics , Male , Risk , Tibia/diagnostic imaging , Tomography, X-Ray Computed , White People
18.
Br J Nutr ; 103(4): 561-8, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19781123

ABSTRACT

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.


Subject(s)
Bone Density Conservation Agents/metabolism , Calcium, Dietary/metabolism , Calcium/metabolism , Diet/adverse effects , Parathyroid Hormone/blood , Phosphorus, Dietary/adverse effects , Adult , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/urine , Bone Resorption/blood , Bone Resorption/metabolism , Calcium/administration & dosage , Calcium/urine , Calcium, Dietary/administration & dosage , Cross-Sectional Studies , Diet Records , Female , Homeostasis , Humans , Micronutrients , Minerals , Nutritional Status , Osteoporosis/prevention & control , Phosphorus, Dietary/administration & dosage , Phosphorus, Dietary/metabolism , Reference Values
19.
Br J Nutr ; 102(10): 1507-12, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19811695

ABSTRACT

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.


Subject(s)
Cardiovascular Diseases/epidemiology , Carotid Arteries/anatomy & histology , Diet , Tunica Intima/anatomy & histology , Adolescent , Adult , Aging , Carotid Arteries/drug effects , Child , Child, Preschool , Cohort Studies , Cross-Sectional Studies , Female , Humans , Male , Nutritional Physiological Phenomena , Tunica Intima/drug effects , Young Adult
20.
Public Health Nutr ; 12(10): 1885-92, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19216809

ABSTRACT

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.


Subject(s)
Calcium/blood , Food Additives/adverse effects , Parathyroid Hormone/blood , Phosphates/adverse effects , Phosphorus, Dietary/adverse effects , Phosphorus/adverse effects , Adult , Animals , Cheese , Cross-Sectional Studies , Diet , Female , Finland , Humans , Milk , Multivariate Analysis , Phosphates/administration & dosage , Phosphorus/administration & dosage , Phosphorus, Dietary/administration & dosage , Premenopause
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