| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 3. |
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| 4. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 5. |
- Zhou, Bin, et al.
(författare)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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| 6. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 7. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 8. |
- Adams, Charleen, et al.
(författare)
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Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
- 2019
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:1, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
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| 9. |
- Boonen, Steven, et al.
(författare)
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Influence of bone remodelling rate on quantitative ultrasound parameters at the calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European men: the European Male Ageing Study (EMAS)
- 2011
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 165:6, s. 977-986
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men. Design: A cross-sectional population-based survey. Methods: Men aged 40-79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (beta C-terminal cross-linked telopeptide (beta-cTX)), total testosterone, total oestradiol (E-2), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dualenergy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres. Results: A total of 3120, mean age 59.9 years (S.D. = 11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E-2 were negatively associated with beta-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both beta-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine. Conclusions: E-2, SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health.
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| 10. |
- Cook, Michael J., et al.
(författare)
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Frailty and bone health in European men
- 2017
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 46:4, s. 635-641
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Tidskriftsartikel (refereegranskat)abstract
- Background: frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health.Methods: men aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Fried's phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre.Results: in total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P< 0.05). Similar results were seen using the FI after categorisation into 'high', 'medium' and 'low' levels of frailty. Using the Fried categorisation, frail men had lower femoral neck bone mineral density (BMD) compared to robust men (P < 0.05), but not lower lumbar spine BMD. Using the FI categorisation, a 'high' level of frailty (FI > 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05).Conclusions: optimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people.
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| 11. |
- Holliday, Kate L., et al.
(författare)
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The ESR1 (6q25) Locus Is Associated with Calcaneal Ultrasound Parameters and Radial Volumetric Bone Mineral Density in European Men
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. Methods: Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. Results: 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. Conclusions: Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.
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| 12. |
- Huhtaniemi, Ilpo T, et al.
(författare)
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Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats.
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- Context: The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive. Objective: To investigate the relationships between health status, various reproductive hormones and the AR CAG repeat length. Design: A multi-national prospective cohort observational study - cross-sectional baseline data. Setting: Population survey of community-dwelling men. Participants: Men (40-79-yr-old; n=3,369) randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2,878 men. Main outcome measures: The correlations of the CAG repeat length with selected endocrine, metabolic and phenotypic parameters related to aging and sex hormone action. Results: Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free and bioavailable levels of testosterone (T) and estradiol (E2). FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids, or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions. Conclusions: The AR CAG repeat length correlates significantly with serum T and E2 of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or near-totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions following aromatization of the higher T levels.
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| 13. |
- Limer, Kate L., et al.
(författare)
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Genetic Variation in Sex Hormone Genes Influences Heel Ultrasound Parameters in Middle-Aged and Elderly Men: Results From the European Male Aging Study (EMAS)
- 2009
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Ingår i: Journal of Bone and Mineral Research. - 1523-4681. ; 24:2, s. 314-323
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Tidskriftsartikel (refereegranskat)abstract
- Genes involved in sex hormone pathways are candidates for influencing bone strength. Polymorphisms in these genes were tested for association with heel quantitative ultrasound (QUS) parameters in middle-aged and elderly European men. Men 40-79 yr of age were recruited from population registers in eight European centers for the European Male Aging Study (EMAS). Polymorphisms were genotyped in AR, ESR1, ESR2, CYP19A1, CYP17A1, SHBG, SRD5A2, LHB, and LHCGR. QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the heel and used to derive BMD. The relationships between Q US parameters and polymorphisms were assessed using linear regression adjusting for age and center. A total of 2693 men, with a mean age of 60.1 +/- 11.1 (SD) yr were included in the analysis. Their mean BUA was 80.0 +/- 18.9 dB/Mhz, SOS was 1550.2 +/- 34.1. m/s, and BMD was 0.542 +/- 0.141 g/cm(2). Significant associations were observed between multiple SNPs in a linkage disequilibrium (LD) block within CYP19A1, peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (beta = -0.016, p = -0.005) and homozygotes (beta = -0.029, p = 0.001). The results for BUA and SOS were similar. Significant associations with QUS parameters were also observed for the CAG repeat in AR and SNPs in CYP17A1, LHCGR, and ESR1 Our data confirm evidence of association between bone QUS parameters and polymorphisms in CYP79A1, as well as modest associations with polymorphisms in CYP17A1, ESR1, LHCGR, and AR in a population sample of European men; this supports a role for genetically determined sex hormone actions in influencing male bone health.
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| 14. |
- Pye, Stephen R., et al.
(författare)
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Influence of Insulin-Like Growth Factor Binding Protein (IGFBP)-1 and IGFBP-3 on Bone Health: Results from the European Male Ageing Study
- 2011
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 88:6, s. 503-510
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine the influence of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3, and IGF-I on calcaneal ultrasound parameters in middle-aged and elderly European men. Men aged 40-79 years were recruited from population registers for participation in the European Male Ageing Study (EMAS). Subjects were invited by letter to complete a postal questionnaire and to attend for an interviewer-assisted questionnaire, quantitative ultrasound (QUS) of the calcaneus, and a fasting blood sample from which serum levels of IGFBP-1, IGFBP-3, IGF-I, estradiol (E-2), and SHBG were assayed. The questionnaires included the Physical Activity Scale for the Elderly (PASE) and questions about smoking and alcohol consumption. Estimated bone mineral density (eBMD) was derived as a function of the QUS parameters speed of sound and broadband ultrasound attenuation. Height and weight were measured in all subjects. 3057 men, mean age 59.7 years (standard deviation 11.0) were included in the analysis. After adjusting for age, center, and BMI, higher levels of IGFBP-1 were associated with lower eBMD. Higher levels of both IGFBP-3 and IGF-I were associated with higher eBMD. After further adjustment for PASE score, current smoking, alcohol consumption, free E-2, and SHBG, IGFBP-3 and IGF-I, though not IGFBP-1, remained significantly associated with eBMD. IGFBP-1 was associated with bone health, though the effect could be explained by other factors. IGFBP-3 and IGF-I were independent determinants of bone health in middle-aged and elderly European men.
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| 15. |
- Pye, Stephen R., et al.
(författare)
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Influence of Lifestyle Factors on Quantitative Heel Ultrasound Measurements in Middle-Aged and Elderly Men
- 2010
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 86:3, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- We examined the distribution of quantitative heel ultrasound (QUS) parameters in population samples of European men and looked at the influence of lifestyle factors on the occurrence of these parameters. Men aged between 40 and 79 years were recruited from eight European centers and invited to attend for an interviewer-assisted questionnaire, assessment of physical performance, and quantitative ultrasound (QUS) of the calcaneus (Hologic; Sahara). The relationships between QUS parameters and lifestyle variables were assessed using linear regression with adjustments for age, center, and weight. Three thousand two hundred fifty-eight men, mean age 60.0 years, were included in the analysis. A higher PASE score (upper vs. lower tertile) was associated with a higher BUA (beta coefficient = 2.44 dB/Mhz), SOS (beta = 6.83 m/s), and QUI (beta = 3.87). Compared to those who were inactive, those who walked or cycled more than an hour per day had a higher BUA (beta = 3.71 dB/Mhz), SOS (beta = 6.97 m/s), and QUI (beta = 4.50). A longer time to walk 50 ft was linked with a lower BUA (beta = -0.62 dB/Mhz), SOS (beta = -1.06 m/s), and QUI (beta = -0.69). Smoking was associated with a reduction in BUA, SOS, and QUI. There was a U-shaped association with frequency of alcohol consumption. Modification of lifestyle, including increasing physical activity and stopping smoking, may help optimize bone strength and reduce the risk of fracture in middle-aged and elderly European men.
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| 16. |
- Pye, Stephen R, et al.
(författare)
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Low heel ultrasound parameters predict mortality in men: results from the European Male Ageing Study (EMAS).
- 2015
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 1468-2834 .- 0002-0729. ; 44:5, s. 801-807
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Tidskriftsartikel (refereegranskat)abstract
- low bone mineral density measured by dual-energy x-ray absorptiometry is associated with increased mortality. The relationship between other skeletal phenotypes and mortality is unclear. The aim of this study was to determine the relationship between quantitative heel ultrasound parameters and mortality in a cohort of European men.
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| 17. |
- Roshandel, Delnaz, et al.
(författare)
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A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study
- 2011
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: A number of single nucleotide polymorphisms (SNPs) have been associated with broadband ultrasound attenuation (BUA) and speed of sound (SOS) as measured by quantitative ultrasound (QUS) at the calcaneus in the Framingham 100K genome-wide association study (GWAS) but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA) was also tested. Methods: Men aged 40-79 years (N = 2960) were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS). QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS), femoral neck (FN) and total hip (TH) BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p < 10(-4) were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD) bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p < 0.05 indicated replication. Results: Thirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (beta(SD) = 0.07, p = 0.032) but not BUA (beta(SD) = 0.02, p = 0.505) and is located in the 3'UTR of WDR77 (WD repeat domain 77) also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (beta(SD) = -0.22, p = 0.014), FN (beta(SD) = -0.31, p = 0.001) and TH (beta(SD) = -0.36, p = 0.002) in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL. Conclusions: We found suggestive evidence of association between a single SNP located in the 3'UTR of WDR77 with calcaneal ultrasound parameters. The majority of SNPs, associated with QUS parameters
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| 18. |
- Roshandel, Delnaz, et al.
(författare)
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Genetic Variation in the RANKL/RANK/OPG Signaling Pathway Is Associated With Bone Turnover and Bone Mineral Density in Men
- 2010
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:8, s. 1830-1838
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r(2) >= 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMDa) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (beta = 1.83, p = .004) and CTX-I (beta = 17.59, p = 4.74 x 10(-4)), and lower lumbar spine BMDa (beta = -0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (beta = -1.84, p = .003) and CTX-I (beta = -27.02, p = 6.06 x 10(-8)) and higher ultrasound BMD at the calcaneus (beta = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. (c) 2010 American Society for Bone and Mineral Research.
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| 19. |
- Roshandel, Delnaz, et al.
(författare)
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Influence of Polymorphisms in the RANKL/RANK/OPG Signaling Pathway on Volumetric Bone Mineral Density and Bone Geometry at the Forearm in Men
- 2011
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 89:6, s. 446-455
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Tidskriftsartikel (refereegranskat)abstract
- We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) a parts per thousand yen 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (beta [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (beta [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (beta [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (beta [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (beta [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (beta [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (beta [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (beta [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.
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| 20. |
- Roshandel, Delnaz, et al.
(författare)
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Polymorphisms in Genes Involved in the NF-kappa B Signalling Pathway Are Associated with Bone Mineral Density, Geometry and Turnover in Men
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-kappa B cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods: Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r(2) >= 0.8) within MAP3K14 (+/-10 kb) were genotyped in 2359 men aged 40-79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre. Results: We validated the associations between SNPs in GPR177 and BMDa previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMDa, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMDa, vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS. Conclusion: Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-kappa B signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health.
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| 21. |
- Vanderschueren, Dirk, et al.
(författare)
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Active Vitamin D (1,25-Dihydroxyvitamin D) and Bone Health in Middle-Aged and Elderly Men: The European Male Aging Study (EMAS).
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:3, s. 995-1005
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Tidskriftsartikel (refereegranskat)abstract
- Context:There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] on bone health including turnover.Objective:The objective of the study was to determine the influence of 1,25(OH)(2)D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.Design, Setting, and Participants:Men aged 40-79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)(2)D, 25(OH)D, and PTH were measured. 1,25(OH)(2)D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.Main Outcome Measure(s):QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.Results:A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)(2)D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)(2)D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)(2)D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)(2)D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.Conclusions:Serum 1,25(OH)(2)D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)(2)D and low 25(OH)D is associated with the poorest bone health.
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| 22. |
- Hackett, Jamie A., et al.
(författare)
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Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline
- 2012
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Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 139:19, s. 3623-3632
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Tidskriftsartikel (refereegranskat)abstract
- Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of the comprehensive epigenetic reprogramming that occurs during PGC development. 5mC plays an important role in maintaining stable gene silencing and repression of transposable elements (TE) but it is not clear how the extensive loss of DNA methylation impacts on gene expression and TE repression in developing PGCs. Using a novel epigenetic disruption and recovery screen and genetic analyses, we identified a core set of germline-specific genes that are dependent exclusively on promoter DNA methylation for initiation and maintenance of developmental silencing. These gene promoters appear to possess a specialised chromatin environment that does not acquire any of the repressive H3K27me3, H3K9me2, H3K9me3 or H4K20me3 histone modifications when silenced by DNA methylation. Intriguingly, this methylation-dependent subset is highly enriched in genes with roles in suppressing TE activity in germ cells. We show that the mechanism for developmental regulation of the germline genome-defence genes involves DNMT3B-dependent de novo DNA methylation. These genes are then activated by lineage-specific promoter demethylation during distinct global epigenetic reprogramming events in migratory (~E8.5) and post-migratory (E10.5-11.5) PGCs. We propose that genes involved in genome defence are developmentally regulated primarily by promoter DNA methylation as a sensory mechanism that is coupled to the potential for TE activation during global 5mC erasure, thereby acting as a failsafe to ensure TE suppression and maintain genomic integrity in the germline.
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| 23. |
- Lindh, Christina, et al.
(författare)
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Combination of radiographic measurement of cortical width and clinical risk index for diagnosis of osteoporosis : the OSTEDENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured by an Active Shape Model (ASM) method in combination with a clinical risk index, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry (DXA) of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. A questionnaire was completed for each subject to identify factors related to osteoporosis risk and calculate a clinical risk index (OSIRIS). A manually initialised ASM method was used to derive cortical width measurements from each radiograph. ROC analysis was used to identify the most effective clinical index. Logistic regression analysis was used to build a model, with the presence or absence of osteoporosis as the dichotomous dependent variable and OSIRIS and the radiographic data as independent variables. Results: ROC analysis gave an Az value for OSIRIS of 0.841 (95% CI: 0.811 to 0.868). The sensitivity and specificity of the combined radiographic-clinical risk assessment were 38.6% and 97.9% respectively. Conclusions: Combining the cortical width measurement and the clinical risk index provided a high specificity method for detection of subjects with osteoporosis, although sensitivity was modest. This model would be most suitable for use in the context of restricted availability of DXA. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 24. |
- Lindh, Christina, et al.
(författare)
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Mandibular cortical index for osteoporosis diagnosis : the OSTEODENT project
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: to determine the diagnostic validity of the mandibular cortical index (MCI) for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Five observers, all oral radiologists but of different experience, made an assessment of porosity of the cortex of the lower border of the mandible using MCI. Results: Data of 661 subjects (mean age 54.8y; sd = 6.19y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. MCI data for each observer were dichotomosed so that MCI grade 3 indicated a positive test result and grades 1 and 2 a negative test result. The sensitivities and specificties of MCI for osteoporosis diagnosis were determined: Osteoporosis at any site Osteoporosis at femoral neck Observer Sensitivity (%) Specificity (%) Sensitivity (%) Specificity (%) 1 24.8 93.3 27.3 91.3 2 23.4 93.2 24.2 91.3 3 23.4 91.5 24.2 89.8 4 20.6 99.8 22.7 91.8 5 19.1 91.1 22.7 90.3 Interobserver repeatability (using weighted Kappa) showed a range of 0.183 to 0.780, with a median value of 0.467. This median indicated moderate agreement. Conclusions: MCI had low sensitivity but high specificity for diagnosis of osteoporosis. This high specificity might prove to be more appropriate for use in primary dental care than using a different diagnostic threshold. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 25. |
- Lindh, Christina, et al.
(författare)
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ROC analysis of automatically measured mandibular cortical width from panoramic radiographs for diagnosis of osteoporosis : the OSTEDENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- 1School of Dentistry and 2Imaging Science and Biomedical Engineering, The University of Manchester, United Kingdom 3School of Dentistry, Oral Pathology and Maxillofacial Surgery, Oral Imaging Centre, Katholieke Universiteit Leuven, Belgium 4Oral Diagnosis and Radiology, The National and Kapodistrian University of Athens, Greece 5Oral Radiology, Malmö University, Sweden 6Oral Radiology, ACTA, Amsterdam, The Netherlands Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured by Active Shape Model (ASM) methods, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Two ASM methods, one entirely automatic and one manually initialised, were used to derive measurements of mandibular cortical width. ROC analysis was used to determine the diagnostic ability of manual and ASM methods. Results: 652 subjects were examined (mean age 54.9y; sd=6.10), with 140 (21.5%) being classified as having osteoporosis. Using the manually initialized ASM method, Az values for the diagnosis of osteoporosis at any site and at femoral neck alone were 0.816 (95% CI: 0.784 to 0.845) and 0.835, (95% CI: 0.805-0.863), respectively. Using the automatically initialized ASM method, the Az values for the diagnosis of osteoporosis at any site and at the femoral neck alone were 0.759 (95% CI: 0.724-0.791) and 0.805 (95% CI: 0.773 -0.835), respectively. The difference in Az of the two methods for the diagnosis of osteoporosis at either the hip or spine was significant (p<0.001), but not significant at the femoral neck alone. Conclusions: ASM-based methods ofmandibular cortical width measurement were effective in the diagnosis of osteoporosis. The manually initialized method, involving a small amount of user interaction, performed best. Further analysis is necessary to establish the appropriate diagnostic threshold for clinical use. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 26. |
- Lindh, Christina, et al.
(författare)
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ROC analysis of densitometric measurements on intraoral radiographs for detection of osteoporosis as part of the OSTEDENT study
- 2006
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To determine the diagnostic validity of mandibular and maxillary bone density, measured between the premolars (mm Aleq) in detecting osteoporosis at the hip or lumbar spine. Methods: Female subjects between 45 and 70 years of age, were recruited from 4 European centres. They underwent dual x-ray energy absorptiometry of the hip and lumber spine, to provide a gold standard diagnosis of osteoporosis. In addition, intra-oral radiography of upper and lower right premolar region was performed, using an aluminum wedge as a densitometric reference. Jaw bone density in 4 selected regions of interest (ROI) was determined using dedicated software Osteop (Nackaerts et al 2005**). Two ROIs were determined between the upper premolar teeth and another 2 between the lower premolars. 5 observers performed the analysis. Intra- and inter-observer differences and ROC curves were analyzed. Results: Results from 660 subjects (mean age 54.8y; sd 6.19) were suitable for analysis. 136 of these subjects were classified as having osteoporosis. For ROC analysis, measurement data from all observers were averaged, since there was no significant inter-observer difference. Az values as well as 95% confidence intervals are shown in the table: Detecting osteoporosis at any site (spine, hip, femoral neck): ROI1 upper jaw Az 0.691 (0.653 to 0.726) ROI2 upper jaw Az 0.708 (0.671 to 0.743) ROI1 lower jaw Az 0.709 (0.672 o 0.745) ROI2 lower jaw Az 0.702 (0.655 to 0.738) None of the differences in Az between sites was statistically significant (p always > >0.05). Conclusions: Density of the premolar region expressed in mm Aleq is a fair indication for the presence of osteoporosis. More extensive analysis of the OSTEODENT results might reveal an even better predictive tool for osteoporosis screening. **Nackaerts O, Jacobs R, Pillen M, Engelen L, Gijbels F, Devlin H, Lindh C, Nicopolou-Karayianni K, van der Stelt P, Horner K. Accuracy and precision of a densitometric tool for jaw bone. DentoMaxilloFacial Radiology. In press This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 27. |
- Lindh, Christina, et al.
(författare)
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ROC analysis of directly measured mandibular cortical width from panoramic radiogarphs for diagnosis of osteoporosis : the OSTEODENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured directly by observers, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Five observers, all oral radiologists but of different experience, made manual measurements of width of the mandibular lower border cortex below the mental foramina bilaterally. Results: Data of 661 subjects (mean age 54.8y; sd = 6.19y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. Az values are given below: Osteoporosis at any site Osteoporosis at femoral neck Observer Az (se) 95% CI Az (se) 95% CI 1 0.782 0.748-0.813 0.804 0.771-0.833 2 0.766 0.731-0.799 0.757 0.722-0.791 3 0.756 0.721-0.788 0.790 0.757-0.821 4 0.746 0.711-0.779 0.762 0.727-0.794 5 0.710 0.673-0.744 0.752 0.718-0.785 A diagnostic threshold of 3mm resulted in a sensitivity of 50.7% and a specificity of 80.4% (data for median observer, 2). Mean within-subject variance for the five observers was 0.126mm (sd = 0.355mm). Repeatability is the difference between two measurements made by any pair of observers for the same subject and was expected to be less than 0.983 mm for 95% of pairs of observations. Conclusions: Direct measurement of mandibular cortical width was diagnostically effective in diagnosis of osteoporosis. However, repeatability may be a problem in clinical use. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 28. |
- Lindh, Christina, et al.
(författare)
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Trabecular pattern in intraoral radiographs as a sign of osteoporosis : the OSTEODENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: The aim of this study was to investigate if the trabecular pattern in intraoral radiographs, assessed by five observers, could serve as an indicator of osteoporosis. Methods: Six hundred and seventy one women (45 - 70 yrs) from four European centers were included in the study and examined with intraoral radiographs in the right upper and lower premolar region. The patients also underwent examinations with central dual energy X-ray absorptiometry (DXA) of the hip and lumbar spine. Five observers assessed the trabecular pattern in the intraoral radiographs into one of three classes: dense, heterogeneous or sparse trabecular pattern. The assessments were made with the aid of reference images and the observers underwent a calibration procedure before starting their assessments. The classifications were compared with the true diagnosis of osteoporosis measured using DXA. Results: The sensitivity and specificity for five observers’ assessments of the intraoral radiographs with sparse trabecular pattern as indicative of osteoporosis at either hip or spine are given in the table below. The values are calculated for patients diagnosed as having osteoporosis at any of the examined sites. Upper jaw Lower jaw Observer Sensitivity Specificity Sensitivity Specificity 1 22.2 90.2 13.2 94.5 2 22.6 94.8 15.8 94.2 3 26.5 91.6 28.1 86.7 4 36.3 87.4 30.2 82.4 5 35.3 93.7 39.1 95.6 If the cut-off included either “heterogeneous” or “sparse” trabeculation then a higher sensitivity was achieved (90.6 – 73.7) but a lower specificity (49.4 – 26.2). Conclusion: Assessment of sparse trabecular pattern on intraoral radiographs offered a combination of low sensitivity but high specificity for osteoporosis diagnosis. If it is assumed that high specificity is preferred for osteoporosis assessment by dentists, then this method may have potential for clinical use, although inter-observer variability may be a problem. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 29. |
- Nackaerts, Olivia, et al.
(författare)
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Osteoporosis detection using intraoral densitometry
- 2008
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Ingår i: Dento-Maxillo-Facial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 37:5, s. 282-287
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine the diagnostic accuracy of mandibular and maxillary bone density in detecting osteoporosis using receiver operating characteristic (ROC) analysis. METHODS: 671 women between 45 years and 70 years of age underwent dual energy X-ray absorptiometry (DXA) of the hip and lumbar spine. This was the gold standard for diagnosing osteoporosis. Intraoral radiography of the upper and lower right premolar region was performed, using an aluminium wedge as a densitometric reference. Jaw bone density was determined using dedicated software. Observer differences and ROC curves were analysed. RESULTS: For detecting osteoporosis using jaw bone density, the area under the ROC curve (A(z)) was 0.705. For separate analysis of mandibular and maxillary films, sensitivity varied from 33.9% to 38.7% and specificity from 83.5% to 85.3% when using a threshold of 4.3 mm Al equivalent. CONCLUSIONS: Density of the premolar region reaches a fair diagnostic accuracy, which might improve when including additional factors in the analysis and refining the densitometric tool.
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| 30. |
- Reddington, James P, et al.
(författare)
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Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes
- 2013
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 14:3, s. R25-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: DNA methylation and the Polycomb repression system are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear.RESULTS: By genome-wide mapping of the Polycomb Repressive Complex 2-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and Polycomb Repressive Complex 2 from Polycomb target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression.CONCLUSIONS: An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining Polycomb Repressive Complex 2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease.
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