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Sökning: WFRF:(Borghs Herman)

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1.
  • Boonen, Steven, et al. (författare)
  • 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
  • Ingår i: European Journal of Endocrinology. - : Society of the European Journal of Endocrinology. - 1479-683X. ; 165:6, s. 977-986
  • 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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2.
  • Cook, Michael J., et al. (författare)
  • Frailty and bone health in European men
  • Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729. ; 46:4, s. 635-641
  • 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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3.
  • Holliday, Kate L., et al. (författare)
  • The ESR1 (6q25) Locus Is Associated with Calcaneal Ultrasound Parameters and Radial Volumetric Bone Mineral Density in European Men
  • 2011
  • Ingår i: PLoS ONE. - : Public Library of Science. - 1932-6203. ; 6:7
  • 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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4.
  • Huhtaniemi, Ilpo T, et al. (författare)
  • Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats.
  • 2009
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 1945-7197. ; 94, s. 277-284
  • 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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5.
  • Limer, Kate L., et al. (författare)
  • 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
  • Ingår i: Journal of Bone and Mineral Research. - : AMBMR. - 1523-4681. ; 24:2, s. 314-323
  • 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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6.
  • Nackaerts, Olivia, et al. (författare)
  • Osteoporosis detection using intraoral densitometry
  • 2008
  • Ingår i: Dento-Maxillo-Facial Radiology. - 0250-832X .- 1476-542X. ; 37:5, s. 282-287
  • 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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7.
  • Pye, Stephen R., et al. (författare)
  • Influence of Insulin-Like Growth Factor Binding Protein (IGFBP)-1 and IGFBP-3 on Bone Health: Results from the European Male Ageing Study
  • 2011
  • Ingår i: Calcified Tissue International. - : Springer. - 1432-0827. ; 88:6, s. 503-510
  • 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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8.
  • Pye, Stephen R., et al. (författare)
  • Influence of Lifestyle Factors on Quantitative Heel Ultrasound Measurements in Middle-Aged and Elderly Men
  • 2010
  • Ingår i: Calcified Tissue International. - : Springer. - 1432-0827. ; 86:3, s. 211-219
  • 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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9.
  • Roshandel, Delnaz, et al. (författare)
  • A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study
  • 2011
  • Ingår i: BMC Medical Genetics. - : BioMed Central (BMC). - 1471-2350. ; 12
  • 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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10.
  • Roshandel, Delnaz, et al. (författare)
  • Genetic Variation in the RANKL/RANK/OPG Signaling Pathway Is Associated With Bone Turnover and Bone Mineral Density in Men
  • 2010
  • Ingår i: Journal of Bone and Mineral Research. - : AMBMR. - 1523-4681. ; 25:8, s. 1830-1838
  • 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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