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- Bratteby, L E, et al.
(författare)
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Whole-body mineral measurements in Swedish adolescents at 17 years compared to 15 years of age.
- 2002
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Ingår i: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 91:10, s. 1031-8
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To provide reference data for bone mineral variables in 15- and 17-y-old adolescents and to analyse the relationships between these variables and measures of bone and body size, gender, puberty, growth, various lifestyle and environmental factors and socioeconomic background.METHODS: In the same 321 randomly selected adolescents (147 boys and 174 girls) living in two different regions of Sweden, the total bone mineral content (TBMC), bone area (BA) and total bone mineral density (TBMD) were assessed by dual-energy X-ray absorptiometry at ages 15 and 17 y. The effects of bone and body size, gender, growth, sexual maturity, physical activity, region of domicile, social conditions, food habits, smoking and alcohol intake on TBMC and TBMD were examined in multivariate analyses.RESULTS: In the 15-y-old adolescents, BA, height, gender, physical activity, maturity and weight explained 91% and 48%, of the variance in TBMC and TBMD, respectively. In similar analyses in the 17-y-olds, the corresponding figures were 92% and 62%, respectively, when BA, height, growth, physical activity, gender and region emerged as significant in the model. In all these analyses, BA explained most of the variance in TBMC and TBMD. No significant reduction of variance was found when different measures of social conditions, smoking, food habits, alcohol or dietary intakes of energy, calcium or vitamin D were included in the models. The reason why region of domicile had a significant impact on TBMC in the 17-y-olds is not known. The fact that the normal fluoride concentration in drinking water (1.1 mg/L) is 10 times higher in the region where TBMC was higher than in the other region is an interesting observation.CONCLUSION: Almost 90% of the variance in TBMC and 50% of that in TBMD was explained by measures of bone and body size and only a few percent by gender, physical activity, Tanner stage, growth and region of domicile.
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- Grundberg, E, et al.
(författare)
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A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:12, s. 6173-6178
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Tidskriftsartikel (refereegranskat)abstract
- Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture, and the trait is under genetic control by a large number of genes. It is recognized that estrogen plays an important role in the maintenance of bone mass by binding to estrogen receptor a (ERa). RIZ1 has previously been shown to be a specific ERa coactivator and strongly enhances its function both in vivo and in vitro. We performed in vitro studies comparing the abilities of RIZ1 P704 polymorphic variants (homozygous presence, P704+; absence, P704-; heterozygosity P704+/- of a proline at position 704) to coactivate the ERa and also examined the polymorphism associated to BMD of 343 Swedish women, aged 20-39 yr. The expression vector containing P704- RIZ1 showed an impaired response in coactivating ERa in a ligand- and dose-dependent manner compared with P704+ RIZ (P < 0.0001). The genotype frequencies were 19% (P704+), 32% (P704-), and 49% (P704+/-) and were in Hardy-Weinberg equilibrium. BMD at the heel was higher in the P704+ genotype group than in the P704+/- group (P = 0.02), which was evident also after corrections for fat and lean mass (P = 0.03). We conclude that RIZ1 may be a new candidate gene for involvement in the variation seen in BMD.
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| 8. |
- Grundberg, E, et al.
(författare)
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Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men
- 2007
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:6, s. 829-837
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Tidskriftsartikel (refereegranskat)abstract
- Summary Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men. Introduction The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men. Methods The cohorts used were MrOS Sweden (n = 3014, aged 69–81 years) and MrOs Hong Kong (n = 2000, aged > 65 years) and the Swedish GOOD study (n = 1068, aged 18–20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay. Results When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p < 0.05). The Val667Met SNP was not polymorphic in the Hong Kong population and thus were not included. There were no associations between the Ala1330Val SNP and bone phenotypes in the study populations. No associations between the LRP5 polymorphisms and self-reported fractures were seen in MrOs Sweden. Conclusions Results from these three large cohorts indicate that the Val667Met polymorphism but not the Ala1330Val contributes to the observed variability in BMD in the Swedish populations.
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| 11. |
- Lantz, H, et al.
(författare)
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Differences in whole body measurements by DXA-scanning using two Lunar DPX-L machines
- 1999
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Ingår i: International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. - : Springer Science and Business Media LLC. - 0307-0565. ; 23:7, s. 764-70
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare bone mineral and body composition results of two dual-energy X-ray absorptiometry (DXA) instruments from the same manufacturer.SETTINGS: The Medical departments of Sahlgrenska University Hospital, Göteborg and University Hospital, Uppsala, Sweden.DESIGN: Unique aluminium spine phantoms (Phant A and B) delivered with each DXA machine (DXA-A and DXA-B) were cross-checked on the other machine by using the 'AP spine mode'. Eight adolescents were examined on both instruments within 5 h to ascertain total body variables by using standard, as well as extended, modes of analysis. All these double-examinations were undertaken on two occasions, before and after exchange of a detector on the DXA-B.SUBJECTS: Four males and four females aged 15.4-19.2 y with normal body weights, were examined on both occasions. On each occasion, the first examination was performed in Göteborg on four individuals and in Uppsala on four individuals.RESULTS: On the first occasion the phantom measurements resulted in much lower bone mineral density (BMD) values on the DXA-B than on the DXA-A. Later it was detected that a so-called R-value and the corresponding '%-fat' value were out of range on the DXA-B. After exchange of detector, the difference in phantom BMD-values between the two machines had diminished. On the first occasion in vivo BMD values were lowest on the DXA-B (P < 0.01), while on the second occasion they were significantly lower on the DXA-A (P < 0.05). Soft tissue differences were greater after detector exchange and as compared to DXA-A, DXA-B underestimated body fat by 3.5 kg (13.2 vs 9.7 kg, P < 0.001) and overestimated lean tissue mass by 3.8 kg (47.1 vs 50.9 kg, P < 0.001) on the second occasion.CONCLUSIONS: The differences in results between two apparently identical Lunar DPX-L machines were not acceptable. In multicenter studies, it may be necessary to standardise results of participating machines into results of one machine by means of regression equations obtained by examining subsamples of individuals on one master machine and other participating instruments.
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- Grundberg, Elin, et al.
(författare)
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The Impact of Estradiol on Bone Mineral Density is modulated by The Specific Estrogen Receptor-{alpha} Cofactor RIZ1 Insertion/Deletion Polymorphism.
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:Mar 13, s. 2300-2306
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Tidskriftsartikel (refereegranskat)abstract
- Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ER -cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ER alpha function in the presence of estrogen. Objective: The objective of the study was to determine whether a RIZ P704 insertion (+)/ deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. Design: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmo OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmo University Hospital, and Uppsala University Hospital. Participants: In total, 4058 men and women, aged 69 -81 yr, were randomly selected from population registries. Main Outcome Measures: BMD(grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. Results: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(+/+) group (r = 0.19 vs. r = 0.08, P < 0.05). Conclusions: These large-scale studies of elderly men and women indicate that the ER alpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.
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| 28. |
- Grundberg, Elin, et al.
(författare)
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Vitamin D receptor 3 ' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: The MrOS study in Sweden and Hong kong
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 22:6, s. 832-840
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Tidskriftsartikel (refereegranskat)abstract
- The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. Introduction: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. Materials and Methods: Here, we reconstructed common haplotypes in the VDR 3 ' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3 ' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. Results: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% Cl, 1.146-2.391;p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (P < 0.05). The VDR gene was also shown to exhibit a 3 ' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. Conclusions: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.
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| 33. |
- MALLMIN, H, et al.
(författare)
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RISK-FACTORS FOR FRACTURES OF THE DISTAL FOREARM - A POPULATION-BASED CASE-CONTROL STUDY
- 1994
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Ingår i: OSTEOPOROSIS INTERNATIONAL. - : SPRINGER-VERLAG LONDON LTD. - 0937-941X. ; 4:6, s. 298-304
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- To evaluate the risk factors for early osteoporosis in consecutive patients with fracture of the distal forearm, a population-based case-control study was carried out using postal questionnaires supplemented by interviews when necessary. All men and women
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| 34. |
- Mellström, Dan, et al.
(författare)
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Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men : MrOS Sweden
- 2006
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 21:4, s. 529-535
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Tidskriftsartikel (refereegranskat)abstract
- The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.
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| 35. |
- Mellström, Dan, 1945, et al.
(författare)
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Older men with low serum estradiol and high serum SHBG have an increased risk of fractures.
- 2008
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Ingår i: Journal of bone and mineral research. - 1523-4681. ; 23:10, s. 1552-60
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n = 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p < 0.001), but not fT, were independently associated with fracture risk. Further subanalyses of fracture type showed that fE2 was inversely associated with clinical vertebral fractures (HR per SD decrease, 1.57; 95% CI, 1.36-1.80), nonvertebral osteoporosis fractures (HR per SD decrease, 1.42; 95% CI, 1.23-1.65), and hip fractures (HR per SD decrease, 1.44; 95% CI, 1.18-1.76). The inverse relation between serum E2 and fracture risk was nonlinear with a strong relation <16 pg/ml for E2 and 0.3 pg/ml for fE2. In conclusion, older Swedish men with low serum E2 and high SHBG levels have an increased risk of fractures.
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| 36. |
- Mellström, Dan, 1945, et al.
(författare)
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Older men with low serum estradiol and high serum SHBG have an increased risk of fractures
- 2008
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Ingår i: J Bone Miner Res. - : Wiley. - 1523-4681 .- 0884-0431. ; 23:10, s. 1552-60
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n = 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p
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| 42. |
- Ribom, Eva L, et al.
(författare)
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Estimation of physical performance and measurements of habitual physical activity may capture men with high risk to fall--data from the Mr Os Sweden cohort.
- 2009
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Ingår i: Archives of gerontology and geriatrics. - : Elsevier BV. - 1872-6976 .- 0167-4943. ; 49:1
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate if clinically usable estimates of physical performance and level of habitual physical activity are associated with fall risk in elderly men. A population-based sample of 3014 randomly selected men aged 69-80 years was recruited to medical centers in Gothenburg, Malmoe, or Uppsala. The level of physical activity and self-reported falls during the preceding 12 months was evaluated using a questionnaire. The physical performance ability was estimated by measurements of handgrip strength, a timed stands test, a 6-m walking test and a 20-cm narrow walk test. Falls were reported in 16.5% of the men. Fallers performed 6.2+/-19.0% (mean+/-standard deviations; S.D.) less in right handgrip measures, 8.8+/-40.6% slower in the timed stands test, 6.8+/-30.8% slower in the 6-m walking test, and 5.3+/-28.8% slower in the 20-cm narrow walk test (all p<0.001, respectively). The odds ratio for falls among men who performed <-3 S.D. or failed compared to the mean (+1 S.D. to -1 S.D.) in the timed stands test was 3.41 (95% CI 2.31-5.02; p<0.001) and 2.46 (95% CI 1.80-3.34; p<0.001) in 20-cm narrow walk test. There were more fallers that never were physical active (73.0% vs. 65.4%, p<0.001) and who were sitting more (6.4+/-2.5 h/day vs. 6.0+/-2.3 h/day, p<0.05) than among the non-fallers. Fallers scored less than non-fallers in all the estimates of physical performance and they were more sedentary in their life style. The report suggests that clinical usable tests of physical performance and evaluation of habitual physical activity in the clinical situation possibly can be used to predict risk of falls in elderly men.
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