Torben Leo Nielsen

Fracture risk is increased in patients with GH deficiency or untreated prolactinomas--a case-control study.

objective The pituitary secretes many hormones of significance to bone turnover and thus skeletal integrity. The aim of this study was to examine fracture risk in patients with pituitary disorders with special reference to GH deficiency and hyperprolactinaemia.

Prevalence of overweight, obesity and physical inactivity in 20- to 29-year-old, Danish men. Relation to sociodemography, physical dysfunction and low socioeconomic status: the Odense Androgen Study

Objective:To assess the prevalence of overweight, obesity and physical inactivity in 20- to 29-year-old men and to analyze whether sociodemography, physical dysfunction and low socioeconomic status are independent correlates of obesity and physical inactivity.Design:Population-based, cross-sectional study.Subjects:Seven hundred and eighty-three Caucasian, Danish men, aged 20–29 years recruited from 2042 respondents in a questionnaire survey of 3000 men, randomly drawn from the Danish Civil Registration System.Methods:Questionnaire, interview and physical examination.Results:The 783 included men and the 2042 questionnaire respondents matched the background population demographically. The 783 men matched the questionnaire respondents as regards BMI, physical activity, chronic disease, medication, smoking, sociodemography and socioeconomic status. The prevalence of overweight and obesity was 31.7 and 7.9%, respectively (World Health Organization criteria). Using waist circumference (WC) cutoffs of 94 and 102 cm, the prevalence was 16.2 and 10.6%, respectively; 24.4% were physically inactive. BMI and WC increased significantly from age 20 to 29 years. Physical activity decreased significantly with age and correlated inversely with WC, but not with BMI. Occupation, geography, partner status, fatherhood and tobacco exposure were independently related with obesity and physical inactivity. Obesity was also related to musculoskeletal complaints, whereas chronic diseases and low educational level were associated with physical inactivity. Age was not independently related with either outcome.Conclusion:In affluent societies, sociodemographic changes may partly explain the age-related decrease in physical activity and the parallel increase in WC and BMI.

Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism.

Objective  Although vitamin D and bone metabolism are closely related, few studies have addressed the effects of vitamin D status on bone in men at time of peak bone mass. The objectives of this study were to evaluate the prevalence of vitamin D inadequacy in a cross‐sectional study in young men and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function.

Similar reference intervals for total testosterone in healthy young and elderly men: results from the Odense Androgen Study.

Ageing in men is associated with changes in levels of sex hormones.

Geographical variation in DXA bone mineral density in young European men and women. Results from the Network in Europe on male osteoporosis (NEMO) study

UNLABELLED We collected population-based young normal hip and spine BMD data from 17 centres across Europe to assess between centre differences and to compare reference values with the US NHANES-III data. There was strong evidence of between country heterogeneity, but not between centres within countries. Hip BMD mean values were lower in European women, but SDs differed little from the NHANES-III USA results in both sexes. It may be necessary to adjust NHANES-III based T-scores by adding/subtracting a country-specific adjustment factor. INTRODUCTION It remains unclear whether young normal BMD reference values specific to an American population can be validly used for T-score calculation in Europeans. METHODS We collected population based BMD data from 1163 men and 329 women aged 19-29 years from 17 centres across Europe to compare mean and SD values with the NHANES-III study USA results. BMD(g/cm2) was measured at the hip and spine using DXA densitometers cross-calibrated with the European Spine Phantom (ESP). The only exclusions were for technically inadequate scans. A linear regression model was used to derive reference values. To allow for direct comparison with published NHANES III study data, the cross-calibrated BMD values were converted using the ESP equations to Hologic QDR 1000 units. RESULTS In men, the overall mean(SD) BMD values expressed in Hologic-QDR1000 units of measurement, were: femoral neck 0.912(0.132); trochanter 0.793(0.124); and L2-L4 spine 1.027(0.123). The respective estimates in women were: 0.826(0.115); 0.670(0.093); and 0.983(0.107). However the I2 statistic for heterogeneity indicated moderate to strong evidence of between-centre heterogeneity. There was, however, no significant heterogeneity observed between centres within countries, suggesting that this variation arose from national differences. Compared to the NHANES III population-based US data, the mean values in women were significantly lower at both sites due to some lower national European means. However, at all sites and in both sexes the SDs were very similar between the US and Europe. There was some evidence that recruiting volunteers resulted in biased values in women. CONCLUSION Our T-score normal values for the lumbar spine (L2-L4) should be more reliable for spine-specific risk assessment than some non-representative normal ranges, and should be evaluated for that purpose in Europe. If T-scores are to be used to compare individual data with ranges seen in normal young subjects of the same nationality, it may be necessary to adjust femoral NHANES III-based T-scores by adding (or subtracting) a country-specific adjustment factor. In risk assessment it is probably sufficient to use NHANES III-based hip T-scores, as supplied for the hip by densitometer manufacturers, interpreting them in light of recent international meta-analysis data on the relationship between BMD and fracture risk.

Chronic diseases in elderly men: underreporting and underdiagnosis

OBJECTIVE prevalence estimates for chronic diseases and associated risk factors are needed for priority setting and disease prevention strategies. The aim of this cross-sectional study was to estimate the self-reported and clinical prevalence of common chronic disorders in elderly men. STUDY DESIGN AND SETTING a questionnaire was sent to a random sample of 4,975 men aged 60-74 years. An age-stratified randomised sample (n = 1,845) of those with complete questionnaires was invited to participate in a telephone interview (n = 864), followed by physical examination (n = 600). Self-reported data on risk factors and disease prevalence were compared with data from hospital medical records. RESULTS physical inactivity, smoking and excessive alcohol intake were reported by 27, 22 and 17% of the study population, respectively. Except for diabetes, all the chronic diseases investigated, including hypertension, musculoskeletal and respiratory diseases were underreported by study participants. Erectile dysfunction and hypogonadism were substantially underreported in the study population even though these diseases were found to affect 48 and 21% of the participants, respectively. CONCLUSIONS the study showed a high prevalence of detrimental life style factors including smoking, excessive alcohol consumption and physical inactivity in elderly Danish men. Except for diabetes and respiratory disease, chronic diseases were underreported and in particular erectile dysfunction and osteoporosis were underdiagnosed in the study population, underlining the importance of awareness of chronic diseases among both the general population and physicians.

The impact of the CAG repeat polymorphism of the androgen receptor gene on muscle and adipose tissues in 20-29-year-old Danish men: Odense Androgen Study

BACKGROUND The number of CAG repeats (CAG(n)) within the CAG repeat polymorphism of the androgen receptor gene correlates inversely with the transactivation of the receptor. OBJECTIVE To examine the impact of CAG(n) on muscle, fat distribution, and circulating androgen levels. Design, settings and participants Population-based, cross-sectional study of 783 Danish men aged 20-29 years. METHODS Genotyping was performed in 767 men. Areas of thigh and lower trunk muscle (muscle(thigh) and muscle(lower trunk)), subcutaneous adipose tissues (SAT(thigh) and SAT(lower trunk)), and deep adipose tissues (i.m. and visceral) were measured in 393 men by magnetic resonance imaging (MRI). Lean body mass (LBM) and fat mass (FM) were measured in all men by whole body dual-energy X-ray absorptiometry (DEXA). The absolute areas acquired by MRI were the main outcomes. The absolute DEXA measurements and relative assessments of both modalities were considered as the secondary outcomes. Results CAG(n) (range: 10-32) correlated inversely with absolute muscle(thigh) (r=-0.108), absolute muscle(lower trunk) (r=-0.132), relative muscle(thigh) (r=-0.128), relative muscle(lower trunk) (r=-0.126), relative LBM(lower extremity) (r=-0.108), and relative LBM(total) (r=-0.082), and positively with relative SAT(thigh) (r=0.137), relative SAT(lower trunk) (r=0.188), relative FM(lower extremity) (r=0.107), and relative FM(total) (r=0.082). These relationships remained significant, controlling for physical activity, smoking, chronic disease, and age. CAG(n) did not correlate with any circulating androgen. CONCLUSIONS The CAG repeat polymorphism affects body composition in young men: absolute muscle(thigh) and absolute muscle(lower trunk) increase as CAG(n) decreases. Expressed relatively, muscle areas and LBM increase, while SAT and FM decrease as CAG(n) decreases. The polymorphism does not affect deep adipose tissues or circulating androgen levels in young men.

Variation in the Kozak sequence of WNT16 results in an increased translation and is associated with osteoporosis related parameters

The importance of WNT16 in the regulation of bone metabolism was recently confirmed by several genome-wide association studies and by a Wnt16 (Wnt16(-/-)) knockout mouse model. The aim of this study was thus to replicate and further elucidate the effect of common genetic variation in WNT16 on osteoporosis related parameters. Hereto, we performed a WNT16 candidate gene association study in a population of healthy Caucasian men from the Odense Androgen Study (OAS). Using HapMap, five tagSNPs and one multimarker test were selected for genotyping to cover most of the common genetic variation in and around WNT16 (MAF>5%). This study confirmed previously reported associations for rs3801387 and rs2707466 with bone mineral density (BMD) at several sites. Furthermore, we additionally demonstrated that rs2908007 is strongly associated with BMD at several sites in the young, elderly and complete OAS population. The observed effect of these three associated SNPs on the respective phenotypes is comparable and we can conclude that the presence of the minor allele results in an increase in BMD. Additionally, we performed re-sequencing of WNT16 on two cohorts selected from the young OAS cohort, based on their extreme BMD values. On this basis, rs55710688 was selected for an in vitro translation experiment since it is located in the Kozak sequence of WNT16a. We observed an increased translation efficiency and thus a higher amount of WNT16a for the Kozak sequence that was significantly more prevalent in the high BMD cohort. This observation is in line with the results of the Wnt16(-/-) mice. Finally, a WNT luciferase reporter assay was performed and showed no activation of the β-catenin dependent pathway by Wnt16. We did detect a dose-dependent inhibitory effect of Wnt16 on WNT1 activation of this canonical WNT pathway. Increased translation of WNT16 can thus lead to an increased inhibitory action of WNT16 on canonical WNT signaling. This statement is in contrast with the known activating effect of canonical WNT signaling on bone formation and suggests a stimulatory effect on bone metabolism via noncanonical WNT signaling. More research is required to not only confirm this hypothesis, but also to further elucidate the role of non-canonical WNT pathways in bone metabolism and the general mechanisms of interplay between the different WNT signaling pathways.

Polymorphisms in the endocannabinoid receptor 1 in relation to fat mass distribution

OBJECTIVE Both animal and human studies have associated the endocannabinoid system with obesity and markers of metabolic dysfunction. Blockade of the cannabinoid receptor 1 (CB1) caused weight loss and reduction in waist size in both obese and type II diabetics. Recent studies on common variants of the CB1 receptor gene (CNR1) and the link to obesity have been conflicting. The aim of the present study was to evaluate whether selected common variants of the CNR1 are associated with measures of obesity and fat distribution. DESIGN AND METHODS The single nucleotide polymorphisms (SNPs) rs806381, rs10485179 and rs1049353 were genotyped, and body fat and fat distribution were assessed by the use of dual-energy X-ray absorptiometry and magnetic resonance imaging in a population-based study comprising of 783 Danish men, aged 20-29 years. RESULTS The rs806381 polymorphism was significantly associated with visceral fat mass (FM) only, whereas the rs1049353 was significantly and directly associated with visceral and intermuscular FM. None of the SNPs analysed were associated with total body FM or subcutaneous FM. CONCLUSION The results point towards a link between common variants of the CNR1 and fat distribution in young men.

The relationship between health-related quality of life, obesity and testosterone levels in older men

BACKGROUND quality of life evaluated by Short-Form 36 (SF-36) is decreased in obesity and hypogonadism, but the importance of regional fat mass is unknown. In the present study, we evaluated associations between SF-36, regional fat deposits and bioavailable testosterone (BioT) in ageing men. METHODS a population-based cross-sectional study in older men. Data included SF-36 questionnaires with the dimensions such as physical function, role limitations physical, bodily pain, general health, vitality, social function, role limitations emotional and mental health. Furthermore, waist, lean body mass (measured by dual X-ray absorptiometry), visceral adipose tissue and subcutaneous adipose tissue (SAT) (measured by magnetic resonance imaging) and BioT were established. RESULTS five hundred and ninety-eight men aged 60-74 years were included. The SF-36 dimensions such as physical function, general health, vitality and role limitations functional were inversely associated with waist and SAT and positively associated with BioT. In multiple regression analysis, waist was the body composition measure with the strongest association with SF-36 dimension scores. CONCLUSION SF-36 dimension scores were more closely associated with central obesity than with BioT. CLINICAL TRIAL REGISTRATION NUMBER www.clinicaltrials.gov, NCT00155961.