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Sökning: WFRF:(Boonen Steven)

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  • McBeth, John, et al. (författare)
  • Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the European Male Ageing Study
  • 2010
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 1468-2060. ; 69:8, s. 1448-1452
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction A study was undertaken to test the hypothesis that musculoskeletal pain is associated with low vitamin D levels but the relationship is explained by physical inactivity and/or other putative confounding factors. Methods Men aged 40-79 years completed a postal questionnaire including a pain assessment and attended a clinical assessment (lifestyle questionnaire, physical performance tests, 25-hydroxyvitamin D3 (25-(OH) D) levels from fasting blood sample). Subjects were classified according to 25-(OH) D levels as 'normal' (>= 15 ng/ml) or 'low' (<15 ng/ml). The relationship between pain status and 25-(OH) D levels was assessed using logistic regression. Results are expressed as ORs and 95% CIs. Results 3075 men of mean (SD) age 60 (11) years were included in the analysis. 1262 (41.0%) subjects were pain-free, 1550 (50.4%) reported 'other pain' that did not satisfy criteria for chronic widespread pain (CWP) and 263 (8.6%) reported CWP. Compared with patients who were pain-free, those with 'other pain' and CWP had lower 25-(OH) D levels (n = 239 (18.9%), n = 361 (23.3) and n = 67 (24.1%), respectively, p < 0.05). After adjusting for age, having 'other pain' was associated with a 30% increase in the odds of having low 25-(OH) D while CWP was associated with a 50% increase. These relationships persisted after adjusting for physical activity levels. Adjusting for additional lifestyle factors (body mass index, smoking and alcohol use) and depression attenuated these relationships, although pain remained moderately associated with increased odds of 20% of having low vitamin D levels. Conclusions These findings have implications at a population level for the long-term health of individuals with musculoskeletal pain.
  • McBeth, John, et al. (författare)
  • Perturbed Insulin-like Growth Factor-1 (IGF-1) and IGF Binding Protein-3 Are Not Associated with Chronic Widespread Pain in Men: Results from the European Male Ageing Study.
  • 2009
  • Ingår i: Journal of Rheumatology. - : J Rheumatol Publ Co. - 0315-162X. ; 36, s. 2523-2530
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine whether perturbations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) were associated with the presence of chronic widespread pain (CWP) in men. METHODS: The European Male Ageing Study (EMAS) is an 8-center population-based study of men aged 40-79 years recruited from population registers. A questionnaire asked about the presence and duration of musculoskeletal pain, from which subjects reporting CWP were identified. Subjects also had an interviewer-assisted questionnaire: levels of physical activity and mood were assessed, and height and weight were measured. IGF-1 and IGFBP-3 were assayed from a fasting blood sample. Logistic regression models were used to determine the association between IGF measures and CWP. Results were expressed as odds ratios or relative risk ratios. RESULTS: A total of 3206 subjects provided full data. Of those, 1314 (39.0%) reported no pain in the past month and 278 (8.3%) reported pain that satisfied criteria for CWP. IGF-1 concentrations were similar among subjects who reported no pain and those with CWP: 131.5 mg/l and 128.4 mg/l, respectively. This was true also for IGFBP-3 (4.3 and 4.3 mg/l). Obesity was associated with low IGF-1 and a high IGFBP-3/IGF-1 ratio, indicating less bioavailable IGF-1, irrespective of pain status. This relationship persisted after adjustment for comorbidities, depression, smoking, alcohol consumption, and quality of life. CONCLUSION: Overall CWP was not associated with perturbations in IGF-1 and IGFBP-3 concentrations. Hypofunctioning of the axis was noted among subjects who were obese and this was not specific to CWP. These data suggest that IGF-1 is unlikely to be etiologically important in relation to CWP, although the relationship with growth hormone remains to be elucidated.
  • Nicholl, Barbara I., et al. (författare)
  • Association of HTR2A Polymorphisms With Chronic Widespread Pain and the Extent of Musculoskeletal Pain
  • 2011
  • Ingår i: Arthritis and Rheumatism. - : John Wiley and Sons Inc.. - 1529-0131. ; 63:3, s. 810-818
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The aim of the current study was to investigate whether genetic variation in genes across the serotoninergic system is associated with chronic widespread pain (CWP) and the number of pain sites reported. Methods. A discovery cohort, with pain data at 3 time points, was used to investigate genetic associations with 2 phenotypes: 1) CWP (at >= 2 time points; n = 164) compared with pain-free controls (at 3 time points; n = 172), and 2) the maximum number of pain sites reported at any 1 of the 3 time points (range of sites 0-29; n = 989). A cohort of 2,285 men for whom a DNA sample and pain data were available (including 203 CWP cases and 929 controls) was used for validation. Pairwise tagging (r(2) > 0.8) single-nucleotide polymorphisms (SNPs) were genotyped. Logistic and zero-inflated negative binomial regression analyses were used to test for SNP associations with CWP and the number of pain sites, respectively. Results. SNPs in HTR2A were associated with both pain phenotypes in the discovery cohort, and a number of these SNP associations were replicated in the validation cohort, some of which were attenuated after adjustment for depression. There was an increased likelihood of having CWP in subjects with 1 or 2 copies of the T allele of rs12584920 (odds ratio [OR] 1.64, 95% confidence interval [95% CI] 1.01-2.60 [P = 0.03] in the discovery cohort, and OR 1.46, 95% CI 1.07-2.00 [P = 0.018] in the validation cohort). A similar association was observed between rs17289394 and the maximum number of pain sites reported in both cohorts. Results from a meta-analysis of the data from the 2 cohorts further strengthened these findings. Conclusion. The findings of this study support the role of HTR2A in the genetic predisposition to musculoskeletal pain.
  • Nicholl, Barbara I., et al. (författare)
  • No evidence for a role of the catechol-O-methyltransferase pain sensitivity haplotypes in chronic widespread pain
  • 2010
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 1468-2060. ; 69:11, s. 2009-2012
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The aim of this study was to investigate the association between the catechol-O-methyltransferase (COMT) 'pain sensitivity' haplotypes and chronic widespread pain (CWP) in two distinct cohorts. Methods Cases of CWP and controls free of pain were selected from two population-based studies: the Epidemiology of Functional Disorders study (EPIFUND) (UK) and the European Male Ageing Study (European). The number of cases and controls were 164 and 172, and 204 and 935, respectively. Identical American College of Rheumatology criteria were used in both studies to ascertain CWP status. The EPIFUND study had three time points and cases were classified as subjects with CWP at two or three time points and controls as those free of pain at all three time points. Four single nucleotide polymorphisms (SNP): rs6269, rs4633, rs4818 and rs4680 (V158M) were genotyped using Sequenom technology. Allele and genotype frequencies were compared and haplotype analysis was conducted using PLINK software. Results No differences in allele or genotype frequencies for any of the four SNP were observed between cases and controls for either cohort. Haplotype analysis also showed no difference in the frequency of haplotypes between cases and controls. Conclusions There was no evidence of association between the COMT 'pain sensitivity' haplotypes and CWP in two population-based cohorts.
  • O'Connor, Daryl B, et al. (författare)
  • Assessment of sexual health in aging men in Europe: Development and validation of the European Male Ageing Study sexual function questionnaire
  • 2008
  • Ingår i: Journal of Sexual Medicine. - : Wiley-Blackwell. - 1743-6109. ; 5:6, s. 1374-1385
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction. Assessment of male sexual dysfunction has been the focus of substantial scientific effort. Less research has focused on the development of instruments for the measurement of sexual functioning in aging men. Aim. The aims of this study were: (i) to characterize the psychometric properties of a new brief, reliable, and valid measure of male sexual functioning for use in a large population survey of middle-aged and elderly European men; and (ii) specifically, to determine whether the new instrument, the European Male Ageing Study-sexual function questionnaire (EMAS-SFQ), discriminates between men with high and low levels of circulating testosterone (T) (total T, free T, and bioavailable T). Method. One thousand six hundred men aged 40-79 years completed the self-administered EMAS-SFQ, the Beck depression inventory, and provided a blood sample for assessment of sex hormones. Eighty-five men aged 35-74 years completed the EMAS-SFQ twice, 2 weeks apart to examine the test-retest reliability of the instrument. Main Outcome Measures. Scores on the EMAS-SFQ in relation to age and T levels. Results. Principal component analysis showed that the EMAS-SFQ had four distinct domains (overall sexual functioning [OSF], masturbation, sexual functioning-related distress, and change in sexual functioning). The instrument demonstrated excellent internal and test-retest reliability, as well as convergent, divergent, and discriminant validity. Men with the lowest levels of total, free, and bioavailable T reported lower OSF scores compared to men with the highest T levels. Conclusion. The EMAS-SFQ is a valid and reproducible instrument, sensitive to age and T levels. It should be suitable for the assessment of sexual health in population samples of men in epidemiological studies of aging.
  • O'Connor, Daryl B, et al. (författare)
  • The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men.
  • 2011
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : Oxford University Press. - 1945-7197. ; 96, s. 1577-1587
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Limited data are available exploring the associations between sex hormones, multiple domains of sexual functioning, and sexual function-related distress in nonpatient samples in Europe. Objectives: The aim of the study was to investigate the relationships between serum testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) and sexual function in a multicenter population-based study of aging in men. Design: Using stratified random sampling, 2838 men aged 40-79 yr completed the European Male Ageing Study-Sexual Function Questionnaire and provided a blood sample for hormone measurements. T, E2, and DHT were measured using gas chromatography-mass spectrometry. Setting: We conducted a community-based population survey in eight European centers. Main Outcome Measures: Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured. Results: Total and free T, but not E2 or DHT, was associated with overall sexual function in middle-aged and older men. E2 was the only hormone associated with sexual function-related distress such that higher levels were related to greater distress. Free T levels were associated with masturbation frequency and erectile dysfunction in the fully adjusted models, such that higher T was associated with less dysfunction and greater frequency. Moreover, there was a T threshold for the relationship between total T, sexual function, and erectile dysfunction. At T concentrations of 8 nmol/liter or less, T was associated with worse sexual functioning, whereas at T levels over 8 nmol/liter, the relationship came to a plateau. Conclusions: These findings suggest that different hormonal mechanisms may regulate sexual functioning (T) vs. the psychological aspects (E2) of male sexual behavior. Moreover, there was a T threshold for overall sexual function such that at levels greater than 8 nmol/liter the relationship between T and sexual function did not become stronger.
  • Ophoff, Jill, et al. (författare)
  • Physical activity in the androgen receptor knockout mouse: evidence for reversal of androgen deficiency on cancellous bone.
  • 2009
  • Ingår i: Biochemical and biophysical research communications. - 1090-2104. ; 378:1, s. 139-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Disruption of the androgen receptor (AR) in male mice reduces cortical bone expansion and muscle mass during puberty and results in high bone turnover-related cancellous osteopenia. We hypothesized that voluntary wheel running during growth is able to rescue the effects of AR disruption on bone. To this end, 5-week-old AR knockout (ARKO) mice were randomized to a running group (cage with running wheel) and a sedentary group (cage without wheel) and followed-up until 16 weeks of age. Voluntary wheel running in ARKO mice did not influence body weight, muscle mass or periosteal bone expansion. Interestingly, voluntary running significantly reduced bone turnover in ARKO mice and prevented cancellous bone loss due to a preservation of trabecular number. Thus, voluntary running in ARKO mice was able to reduce cancellous bone resorption, suggesting that sustained exercise may potentially compensate the effects of androgen disruption on cancellous bone.
  • Orwoll, Eric, et al. (författare)
  • A Randomized, Placebo-Controlled Study of the Effects of Denosumab for the Treatment of Men with Low Bone Mineral Density
  • 2012
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - 0021-972X .- 1945-7197. ; 97:9, s. 3161-3169
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Men with low bone mineral density (BMD) were treated with denosumab.Objective: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment.Design, Subjects, and Intervention: This was a placebo-controlled, phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD.Main Outcome Measure: The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at month 12.Results: Of the 242 randomized subjects (mean age 65 yr), 228 (94.2%) completed 1 yr of denosumab therapy. After 12 months, denosumab resulted in BMD increases of 5.7% at the LS, 2.4% at the total hip, 2.1% at the femoral neck, 3.1% at the trochanter, and 0.6% at the one third radius (adjusted P <= 0.0144 for BMD percent differences at all sites compared with placebo). Sensitivity analyses done by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr osteoporotic fracture risk) demonstrated that the results of the primary endpoint were robust. Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations. Treatment with denosumab significantly reduced serum CTX levels at d 15 (adjusted P < 0.0001). The incidence of adverse events was similar between groups.Conclusions: One year of denosumab therapy in men with low BMD was well tolerated and resulted in a reduction in bone resorption and significant increases in BMD at all skeletal sites assessed.
  • 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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