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| 2. |
- Callréus, Mattias, et al.
(författare)
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Adverse Effects of Smoking on Peak Bone Mass May Be Attenuated by Higher Body Mass Index in Young Female Smokers.
- 2013
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 93:6, s. 517-525
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is associated with postmenopausal bone loss and fracture, but the effect of smoking on bone in younger women is unclear. Peak bone mass is an important determinant for fracture risk; therefore, our aim was to evaluate the association between smoking and bone mass in 25-year-old women, specifically the influence of daily cigarette consumption and total exposure, duration, age at starting smoking, and time since smoking cessation on bone density and fracture risk. Smoking and bone mineral density (BMD) data were available for 1,054 women from the PEAK-25 cohort. Analyses comparing current smokers with women who never smoked were performed using number of cigarettes per day, pack-years, smoking duration, age smoking started, and, for former smokers, age at quitting. BMD did not differ between never, former, and current smokers; and the relative fracture risk in smokers was not significant (relative risk [RR] = 1.2, 95 % confidence interval 0.8-1.9). Among current smokers, BMD decreased with a dose response as cigarette consumption increased (femoral neck p = 0.037). BMD was not significantly lower in young women who had smoked for long duration or started smoking early (p = 0.07-0.64); long duration and early start were associated with higher body mass index (BMI; p = 0.038). Lower BMD persisted up to 24 months after smoking cessation (p = 0.027-0.050), becoming comparable to never-smokers after 24 months. Hip BMD was negatively associated with smoking and dose-dependent on cigarette consumption. Smoking duration was not associated with BMD, although young women with a long smoking history had higher BMI, which might attenuate the adverse effects from smoking.
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| 3. |
- Callréus, Mattias, et al.
(författare)
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Birth weight is more important for peak bone mineral content than for bone density: the PEAK-25 study of 1,061 young adult women.
- 2013
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 24:4, s. 1347-1355
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Tidskriftsartikel (refereegranskat)abstract
- Lower birth weight has a negative association with adult BMC and body composition in young adult Swedish women. INTRODUCTION: The aim of this study was to evaluate the influence of birth weight on peak bone mass and body composition in a cohort of 25-year-old women. METHODS: One thousand sixty-one women participated in this cross-sectional population-based study using dual energy X-ray absorptiometry (DXA) to assess bone mineral content (BMC), bone mineral density (BMD), and body composition (total body (TB), femoral neck (FN), total hip (TH), lumbar spine L1-L4 (LS), and lean and fat mass). Birth weight data was available for 1,047 women and was categorized into tertiles of low (≤3,180 g), intermediate (3,181-3,620 g), and high (≥3,621 g) birth weight. RESULTS: Significant correlations were observed between birth weight and TB-BMC (r = 0.159, p < 0.001), FN-BMC (r = 0.096, p < 0.001), TH-BMC (r = 0.102, p = 0.001), LS-BMC (r = 0.095, p = 0.002), and lean mass (r = 0.215, p < 0.001). No correlation was observed between birth weight and BMD. The estimated magnitude of effect was equivalent to a 0.3-0.5 SD difference in BMC for every 1 kg difference in birth weight (151 g (TB); 0.22 g (FN); 1.5 g (TH), 2.5 kg TB lean mass). The strongest correlations between birth weight and BMC occurred in women with lowest birth weights, although excluding women who weighed <2,500 g at birth, and the correlation remained significant although slightly weaker. CONCLUSIONS: Women with lower birth weight have lower BMC and less lean and fat mass at the age of 25, independent of current body weight. Lower birth weight has a greater negative influence on bone mass than the positive influence of higher birth weight.
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| 4. |
- Callréus, Mattias, et al.
(författare)
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Country-Specific Young Adult Dual-Energy X-Ray Absorptiometry Reference Data Are Warranted for T-Score Calculations in Women: Data From the Peak-25 Cohort.
- 2014
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Ingår i: Journal of Clinical Densitometry. - : Elsevier BV. - 1094-6950. ; 17:1, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to provide normative data for dual-energy X-ray absorptiometry (DXA) in 25-yr-old women and evaluate whether young adult Swedish women have bone mineral density (BMD) comparable with DXA manufacturer reference values and other equivalent populations. BMD at all sites was measured in the population-based Peak-25 cohort (n = 1061 women; age, 25.5 ± 0.2yr). BMD values were standardized (sBMD) and compared against the Third National Health and Nutrition Examination Survey (NHANES III) and other cohorts. Based on the DXA manufacturer-supplied reference values, Z-scores were 0.54 ± 0.98 (femoral neck [FN]), 0.47 ± 0.96 (total hip [TH]), and 0.32 ± 1.03 (lumbar spine [LS]). In comparison with other studies, sBMD was higher in the Peak-25 cohort (FN, 1.5%-8.3%; TH, 3.9%-9.2%; and LS, 2.4%-6.5%) with the exception of trochanter-sBMD which was 2.5% lower compared with NHANES III. The concordance in identifying those in the lowest or highest quartile of BMD was highest between hip measurements (low, 71%-78% and high, 70%-84%), corresponding discordance of 0%-1%. At this age, the correlation between DXA sites was strong (r = 0.62-0.94). BMD in Swedish young adult women is generally higher than has been reported in other equivalently aged European and North American cohorts and suggests that the high fracture incidence in Sweden is not explained by lower peak bone mass. The use of nonregional-specific DXA reference data could contribute to misdiagnosed osteoporosis in elderly women.
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| 5. |
- Callréus, Mattias, et al.
(författare)
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Self-reported recreational exercise combining regularity and impact is necessary to maximize bone mineral density in young adult women : A population-based study of 1,061 women 25 years of age.
- 2012
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 23:10, s. 2517-2526
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Tidskriftsartikel (refereegranskat)abstract
- Recreational physical activity in 25-year-old women in Sweden increases bone mineral density (BMD) in the trochanter by 5.5% when combining regularity and impact. Jogging and spinning were especially beneficial for hip BMD (6.4-8.5%). Women who enjoyed physical education in school maintained their higher activity level at age 25. INTRODUCTION: The aims of this study were to evaluate the effects of recreational exercise on BMD and describe how exercise patterns change with time in a normal population of young adult women. METHODS: In a population-based study of 1,061 women, age 25 (±0.2), BMD was measured at total body (TB-BMD), femoral neck (FN-BMD), trochanter (TR-BMD), and spine (LS-BMD). Self-reported physical activity status was assessed by questionnaire. Regularity of exercise was expressed as recreational activity level (RAL) and impact load as peak strain score (PSS). A permutation (COMB-RP) was used to evaluate combined endurance and impacts on bone mass. RESULTS: More than half of the women reported exercising on a regular basis and the most common activities were running, strength training, aerobics, and spinning. Seventy percent participated in at least one activity during the year. Women with high RAL or PSS had higher BMD in the hip (2.6-3.5%) and spine (1.5-2.1%), with the greatest differences resulting from PSS (p < 0.001-0.02). Combined regularity and impact (high-COMB-RP) conferred the greatest gains in BMD (FN 4.7%, TR 5.5%, LS 3.1%; p < 0.001) despite concomitant lower body weight. Jogging and spinning were particularly beneficial for hip BMD (+6.4-8.5%). Women with high-COMB-RP scores enjoyed physical education in school more and maintained higher activity levels throughout compared to those with low scores. CONCLUSION: Self-reported recreational levels of physical activity positively influence BMD in young adult women but to maximize BMD gains, regular, high-impact exercise is required. Enjoyment of exercise contributes to regularity of exercising which has short- and long-term implications for bone health.
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- Cosman, Felicia, et al.
(författare)
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Determinants of stress fracture risk in United States Military Academy cadets
- 2013
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 55:2, s. 359-366
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior studies have identified some risk factors for stress fracture in athletes and military recruits. Objective: To determine whether historical factors, physical measures, biochemical variables of skeletal metabolism, genetic factors, bone density (BMD) and bone size could predict risk of stress fracture over 4 years in physically fit cadets at the US Military Academy (USMA). Methods: Baseline surveys, assessments of height, weight, scores on the Army Physical Fitness Test, and peripheral BMD were obtained in all cadets (755 men, 136 women), and central BMD in a subset. Blood samples were analyzed for variables of calcium homeostasis, bone turnover, and selected hormones and genetic factors. Stress fractures were adjudicated by review of orthopedic notes and imaging reports. Results: 5.7% of male and 19.1% of female cadets had at least 1 stress fracture (58% metatarsal and 29% tibial), most within 3 months of entry to USMA. In males, risk of stress fracture was higher in those who exercised <7 h per week during the prior year (RR 2.31; CI 1.29,4.12), and in those with smaller tibial cortical area (RR 1.12; CI 1.03,1.23), lower tibial bone mineral content (RR 1.11; CI 1.03,1.20) and smaller femoral neck diameter (RR 1.35, CI 1.01, 1.81). In women, higher stress fracture risk was seen in those with shorter time since menarche (RR 1.44 per year; Cl 1.19, 1.73) and smaller femoral neck diameter (RR 1.16; Cl 1.01, 1.33.). Conclusion: Although prior physical training in men, length of prior estrogen exposure in women and leg bone dimensions in both genders played a role, the maximum variance explained by all of these factors was below 10%. We conclude these factors play a minor role in the development of stress fractures in physically fit USMA cadets. (C) 2013 Elsevier Inc. All rights reserved.
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| 7. |
- Garg, Gaurav, et al.
(författare)
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Variation in the MC4R Gene Is Associated with Bone Phenotypes in Elderly Swedish Women.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is characterized by reduced bone mineral density (BMD) and increased fracture risk. Fat mass is a determinant of bone strength and both phenotypes have a strong genetic component. In this study, we examined the association between obesity associated polymorphisms (SNPs) with body composition, BMD, Ultrasound (QUS), fracture and biomarkers (Homocysteine (Hcy), folate, Vitamin D and Vitamin B12) for obesity and osteoporosis. Five common variants: rs17782313 and rs1770633 (melanocortin 4 receptor (MC4R); rs7566605 (insulin induced gene 2 (INSIG2); rs9939609 and rs1121980 (fat mass and obesity associated (FTO) were genotyped in 2 cohorts of Swedish women: PEAK-25 (age 25, n = 1061) and OPRA (age 75, n = 1044). Body mass index (BMI), total body fat and lean mass were strongly positively correlated with QUS and BMD in both cohorts (r(2) = 0.2-0.6). MC4R rs17782313 was associated with QUS in the OPRA cohort and individuals with the minor C-allele had higher values compared to T-allele homozygotes (TT vs. CT vs.
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| 8. |
- Koller, Daniel L., et al.
(författare)
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Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women
- 2013
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 28:3, s. 547-558
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous single-nucleotide polymorphisms (SNPs) of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to premenopausal white women from four cohorts (n=4061 women, aged 20 to 45 years) to identify genes influencing peak bone mass at the lumbar spine and femoral neck. After imputation, age- and weight-adjusted bone-mineral density (BMD) values were tested for association with each SNP. Association of an SNP in the WNT16 gene (rs3801387; p=1.7x109) and multiple SNPs in the ESR1/C6orf97 region (rs4870044; p=1.3x108) achieved genome-wide significance levels for lumbar spine BMD. These SNPs, along with others demonstrating suggestive evidence of association, were then tested for association in seven replication cohorts that included premenopausal women of European, Hispanic-American, and African-American descent (combined n=5597 for femoral neck; n=4744 for lumbar spine). When the data from the discovery and replication cohorts were analyzed jointly, the evidence was more significant (WNT16 joint p=1.3x1011; ESR1/C6orf97 joint p=1.4x1010). Multiple independent association signals were observed with spine BMD at the ESR1 region after conditioning on the primary signal. Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97 (p<1x105). Our results confirm that several of the genes contributing to BMD variation across a broad age range in both sexes have effects of similar magnitude on BMD of the spine in premenopausal women. These data support the hypothesis that variants in these genes of known skeletal function also affect BMD during the premenopausal period. (c) 2013 American Society for Bone and Mineral Research.
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| 9. |
- Kumar, Jitender, et al.
(författare)
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LRP4 association to bone properties and fracture and interaction with genes in the Wnt- and BMP signaling pathways.
- 2011
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 49, s. 343-348
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a common complex disorder in postmenopausal women leading to changes in the micro-architecture of bone and increased risk of fracture. Members of the low-density lipoprotein receptor-related protein (LRP) gene family regulates the development and physiology of bone through the Wnt/β-catenin (Wnt) pathway that in turn cross-talks with the bone morphogenetic protein (BMP) pathway. In two cohorts of Swedish women: OPRA (n=1002; age 75years) and PEAK-25 (n=1005; age 25years), eleven single nucleotide polymorphisms (SNPs) from Wnt pathway genes (LRP4; LRP5; G protein-coupled receptor 177, GPR177) were analyzed for association with Bone Mineral Density (BMD), rate of bone loss, hip geometry, quantitative ultrasound and fracture. Additionally, interaction of LRP4 with LRP5, GPR177 and BMP2 were analyzed. LRP4 (rs6485702) was associated with higher total body (TB) and lumbar spine (LS) BMD in the PEAK-25 cohort (p=0.006 and 0.005 respectively), and interaction was observed with LRP5 (p=0.007) and BMP2 (p=0.004) for TB BMD. LRP4 also showed significant interaction with LRP5 for femoral neck (FN) and LS BMD in this cohort. In the OPRA cohort, LRP4 polymorphisms were associated with significantly lower fracture incidence overall (p=0.008-0.001) and fewer hip fractures (rs3816614, p=0.006). Significant interaction in the OPRA cohort was observed for LRP4 with BMP2 and GPR177 for FN BMD as well as for rate of bone loss at TB and FN (p=0.007-0.0001). In conclusion, LRP4 and interaction between LRP4 and genes in the Wnt and BMP signaling pathways modulate bone phenotypes including peak bone mass and fracture, the clinical endpoint of osteoporosis.
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| 10. |
- Lagerholm, Sofia, et al.
(författare)
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Genetic loci for bone architecture determined by three-dimensional CT in crosses with the diabetic GK rat.
- 2010
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 47, s. 1039-1047
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Tidskriftsartikel (refereegranskat)abstract
- The F344 rat carries alleles contributing to bone fragility while the GK rat spontaneously develops type-2 diabetes. These characteristics make F344xGK crosses well suited for the identification of genes related to bone size and allow for future investigation on the association with type-2 diabetes. The aim of this study was to identify quantitative trait loci (QTLs) for bone size phenotypes measured by a new application of three-dimensional computed tomography (3DCT) and to investigate the effects of sex- and reciprocal cross. Tibia from male and female GK and F344 rats, representing the parental, F1 and F2 generations, were examined with 3DCT and analyzed for: total and cortical volumetric BMD, straight and curved length, peri- and endosteal area at mid-shaft. F2 progeny (108 male and 98 female) were genotyped with 192 genome-wide microsatellite markers (average distance 10cM). Sex- and reciprocal cross-separated QTL analyses were performed for the identification of QTLs linked to 3DCT phenotypes and true interactions were confirmed by likelihood ratio analysis in all F2 animals. Several genome-wide significant QTLs were found in the sex- and reciprocal cross-separated progeny on chromosomes (chr) 1, 3, 4, 9, 10, 14, and 17. Overlapping QTLs for both males and females in the (GKxF344)F2 progeny were located on chr 1 (39-67cM). This region confirms previously reported pQCT QTLs and overlaps loci for fasting glucose. Sex separated linkage analysis confirmed a male specific QTL on chr 9 (67-82cM) for endosteal area at the fibula site. Analyses separating the F2 population both by sex and reciprocal cross identified cross specific QTLs on chr 14 (males) and chr 3 and 4 (females). Two loci, chr 4 and 6, are unique to 3DCT and separate from pQCT generated loci. The 3DCT method was highly reproducible and provided high precision measurements of bone size in the rat enabling identification of new sex- and cross-specific loci. The QTLs on chr 1 indicate potential genetic association between bone-related phenotypes and traits affecting type-2 diabetes. The results illustrate the complexity of the genetic architecture of bone size phenotypes and demonstrate the importance of complementary methods for bone analysis.
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