Dan Mellström - Academia.edu (original) (raw)

Papers by Dan Mellström

New England Journal of Medicine, 2001

Background Once-daily injections of parathyroid hormone or its amino-terminal fragments increase ... more Background Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown.

Journal of Urology, 2008

We assessed the factors significantly associated with lower urinary tract symptoms (LUTS) in men ... more We assessed the factors significantly associated with lower urinary tract symptoms (LUTS) in men with late-onset hypogonadism (LOH) syndrome. Methods: The study population consisted of 258 patients aged 40 years or older diagnosed with LOH syndrome. Each patient completed a questionnaire study, such as the International Index of Erectile Function (IIEF) 5, Aging Male Score (AMS), and International Prostate Symptom Score (IPSS). Body mass index (BMI), waist size, and muscle volume were measured in all patients, and blood biochemical data, including total cholesterol, triglyceride, hemoglobin A1c, and free testosterone (free T), were also collected. We analyzed the factors that have effect on IPSS. Results: The mean age of the patients was 64.9 ± 8.7 years, and the mean free T value was 7.3 ± 2.2 pg/mL. The critical factors affecting IPSS were IIEF5 score, BMI, muscle volume, age, AMS, and free T-value (P < 0.05). Age showed the strongest significant positive correlation with IPSS (r = 0.321, P < 0.001). Each factor was controlled for age. IIEF5 score and AMS were independent factors affecting IPSS (r = −0.221 and 0.195, respectively, P < 0.05). IPSS showed an inverse correlation with IIEF5, and a positive correlation with AMS. LUTS also had a weak negative correlation with Free T-value but this was not significant (r = −0.121, P = 0.061). Conclusion: Lower urinary tract symptoms were significantly correlated with erectile function and psychological symptoms in men with LOH syndrome.

The Journal of Urology, 2013

We tested the hypothesis that low vitamin D is associated with benign prostatic hyperplasia. We a... more We tested the hypothesis that low vitamin D is associated with benign prostatic hyperplasia. We also studied whether body composition, sex hormones, serum sex hormone-binding globulin, albumin corrected serum calcium, adiponectin and lipid status are associated with benign prostatic hyperplasia. We investigated 184 representative, randomly selected men 72 to 76 years old enrolled in the Gothenburg arm of the Osteoporotic Fractures in Men Study (MrOS). Men with a history of prostate cancer, prostate operation or medication for benign prostatic hyperplasia were excluded from study, leaving 155 available for analysis. A cross-sectional study was performed in which benign prostatic hyperplasia measured by total prostate volume was related to clinical, anthropometric, endocrine and metabolic factors on univariate and multivariate analyses with regression models. Median prostate volume was 40 ml. In multivariate models only 25-OH vitamin D, albumin corrected serum calcium, serum sex hormone-binding globulin and high density lipoprotein cholesterol were significantly and inversely associated with large prostate glands. The current report adds 4 independent factors associated with benign prostatic hyperplasia, including low 25-OH vitamin D, serum calcium, sex hormone-binding globulin and high density lipoprotein cholesterol.

Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT)2B15 and UG... more Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT)2B15 and UGT2B17 glucuronidate androgens and their metabolites.

Journal of Clinical Densitometry, 2014

Cortical porosity increases with age and affects bone strength, but its association with fracture... more Cortical porosity increases with age and affects bone strength, but its association with fracture in older men is unknown. The aim of this study was to investigate whether cortical porosity is associated with prevalent fractures in older men. A subsample of 456 men aged 80.2 ± 3.5 (mean ± SD) years, with available high resolution peripheral quantitative computed tomography measurements at the tibia from the 5-year follow up exam, was drawn from the prospective MrOS Gothenburg study. Dual-energy x-ray absorptiometry was used to measure areal bone mineral density (aBMD). Data on physical activity, calcium intake, medications, diseases, and smoking were collected on questionnaires at the follow-up exam. Of 87 men (19.1%) with fracture at or after age 50 (all fracture group), 52 (11.4%) had had a self-reported fracture before the baseline exam and 35 (7.7%) had had an x-ray verified fracture between baseline and follow-up. Men in the all-fracture group and in the x-ray verified group had 15.8% (13.2 ± 4.9 vs.11.4 ± 3.8%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and 21.6% (14.1 ± 5.2 vs.11.6 ± 3.9%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) higher cortical porosity, respectively, than men in the non-fracture group. The independent associations between bone microstructure parameters and fracture were tested using multivariate logistic regression with age, height, weight, calcium intake, smoking, physical activity, medications, and diseases as covariates. Cortical porosity was independently associated with any fracture (reported or x-ray verified; OR per SD increase: 1.49; 95% confidence interval (CI): 1.17-1.90) and with any x-ray verified fracture alone (OR: 1.73; 95% CI: 1.23-2.42). Including aBMD (spine or hip, respectively) in the multivariate logistic regression above revealed that cortical porosity was associated with any fracture (OR: 1.54; 95% CI: 1.17-2.01) and with x-ray verified fracture alone (OR: 1.49; 95% CI: 1.00-2.22). Cortical porosity was associated with prevalence of fracture even after adjustment for aBMD. This article is protected by copyright. All rights reserved.

PLOS Genetics, 2014

Variation in plasma levels of cortisol, an essential hormone in the stress response, is associate... more Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that ,1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding a1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

The Spine Journal, 2015

The epidemiology, the fracture pattern, and the clinical relevance of prevalent vertebral fractur... more The epidemiology, the fracture pattern, and the clinical relevance of prevalent vertebral fractures in old men are debated wherefore we set out to clarify these issues. Mister Osteoporosis (MrOs) Sweden is a population-based cohort of community-living men aged 69-81 years that includes 3,014 men. Out of these, 1,453 men underwent a lateral radiograph of the thoracic and lumbar spine of which 1,427 were readable and classified by a radiologist, that is the sample size in this study. The men also answered a questionnaire evaluating back pain and limitation in activities of daily living (ADLs) because of back pain during the preceding 12 months in addition with fracture history and life style. Fifteen percentage of the men had at least one prevalent vertebral fracture, but only 1/10th of these were aware of their fracture. Among the men with a fracture, 58% had one, 21% two, 9% three, and 11% four or more fractures. In men with only one fracture, 70% of the fractures were located in the thoracic and 30% in the lumbar spine, 85% had a wedge, 13% a biconcave, and 2% a crush-type configuration; one-quarter had a maximum vertebral body compression degree of less than 24% and one-quarter of more than 38%. Among the men with one or several vertebral fracture, 57% reported back pain compared with 55% in those without a fracture (p=.53). Most ADL functions were similar in the men with or without a prevalent vertebral fracture. In the men with one fracture, there was no difference in the occurrence of back pain depending on the fractured region (p=.49), type of the fracture (p=.77), or degree of compression (p=.85). In men with one or several fractures, there were no significant differences in the presence of back pain in any ages (p=.08), nor there were differences in presence of back pain regarding type (p=.08) or number of fractures (p=.21). A prevalent vertebral fracture is common in old men but has low clinical relevance. There does not seem to be a specific fracture pattern that predisposes for back pain.

The lancet. Diabetes & endocrinology, 2014

Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pre... more Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blo...

Journal of the American College of Cardiology, 2014

The adrenal sex hormone dehydroepiandrosterone (DHEA), which is present in serum mainly as the su... more The adrenal sex hormone dehydroepiandrosterone (DHEA), which is present in serum mainly as the sulfate DHEA-S, is the most abundant steroid hormone in human blood. Its levels decline dramatically with age. Despite the great amount of literature on vascular and metabolic actions of DHEA/-S, evidence for an association between DHEA/-S levels and cardiovascular events is contradictory. This study tested the hypothesis that serum DHEA and DHEA-S are predictors of major coronary heart disease (CHD) and/or cerebrovascular disease (CBD) events in a large cohort of elderly men. We used gas and liquid chromatography-mass spectrometry to analyze baseline levels of DHEA and DHEA-S in the prospective population-based Osteoporotic Fractures in Men study in Sweden (2,416 men, ages 69 to 81 years). Complete cardiovascular clinical outcomes were available from national Swedish registers. During the 5-year follow-up, 302 participants experienced a CHD event, and 225 had a CBD event. Both DHEA and DHEA-S levels were inversely associated with the age-adjusted risk of a CHD event; the hazard ratios and 95% confidence intervals per SD increase were 0.82 (0.73 to 0.93) and 0.86 (0.77 to 0.97), respectively. In contrast, DHEA/-S showed no statistically significant association with the risk of CBD events. The association between DHEA and CHD risk remained significant after adjustment for traditional cardiovascular risk factors, serum total testosterone and estradiol, C-reactive protein, and renal function, and remained unchanged after exclusion of the first 2.6 years of follow-up to reduce reverse causality. Low serum levels of DHEA and its sulfate predict an increased risk of CHD, but not CBD, events in elderly men.

Journal of Internal Medicine, 2014

Blood haemoglobin (Hb) concentration declines in elderly men, whilst the level of the adipocyte-d... more Blood haemoglobin (Hb) concentration declines in elderly men, whilst the level of the adipocyte-derived protein adiponectin increases with age. The association between erythropoiesis and adiponectin in elderly men is unclear. The aim of this study was to determine whether adipokines such as adiponectin and leptin are associated with anaemia and Hb concentration in elderly community-dwelling men. The Gothenburg part of the population-based Swedish Osteoporotic Fractures in Men (MrOS) cohort (n = 1010; median age 75.3 years, range 69-81). We investigated the associations between levels of adiponectin and Hb before and after adjusting for potential confounders [i.e. age, body composition, erythropoietin (EPO), total oestradiol, leptin, cystatin C and iron and B vitamin status]. In these elderly men, age was negatively associated with Hb (r = -0.12, P &amp;amp;amp;amp;lt; 0.001) and positively associated with adiponectin level (r = 0.13, P &amp;amp;amp;amp;lt; 0.001). In age-adjusted partial correlations, Hb and adiponectin levels were negatively correlated (r = -0.20, P &amp;amp;amp;amp;lt; 0.001); this association remained significant after multivariable adjustment for age, body composition, EPO, fasting insulin, sex hormones, leptin and ferritin. Age-adjusted mean adiponectin concentrations were significantly higher in anaemic men (66/1005; Hb &amp;amp;amp;amp;lt;130 g L(-1) ) compared to nonanaemic men (14.0 vs. 11.7 μg mL(-1) , P &amp;amp;amp;amp;lt; 0.05). In multivariate analysis, adiponectin together with EPO, total oestradiol, insulin, albumin, transferrin saturation, HDL cholesterol, cystatin C, total body fat mass and free thyroxine, but not leptin, explained 35% of the variation in Hb level. These results remained essentially unchanged after exclusion of men with diabetes. Serum adiponectin, but not leptin, was negatively and independently associated with Hb. This finding suggests a possible role of adiponectin in the age-related decline in Hb level observed in apparently healthy elderly men.

Stroke, 2002

The aim of this study was to assess the relationship between cardiovascular risk factors, atheros... more The aim of this study was to assess the relationship between cardiovascular risk factors, atherosclerotic disease in the carotid bifurcation, and the risk of stroke and mortality in a representative population sample. One hundred forty-two men and women participated in a population study at ages 70 and 76 years. At age 78, extracranial and intracranial circulation was examined by means of duplex sonography and transcranial Doppler techniques. Mortality and hospitalization for stroke were analyzed over a 5-year follow-up period up to age 83 years. Carotid plaques were identified in 82% of the men and 79% of the women. Bilateral plaques were found in 57% of the men and 46% of the women, and stenosis resulting in &gt;50% diameter reduction occurred in 28% of the men and 17% of the women. Carotid stenosis &gt;75% was observed in 7 subjects (0.5%). Bilateral plaques at age 78 were correlated with systolic blood pressure and ischemic heart disease at age 70 years. The pulsatility index was 1.0 to 1.4 in 63% and &gt; or =1.5 in 13% of the study population. The pulsatility index was correlated with systolic and diastolic blood pressure, serum cholesterol, and triglycerides. Men with bilateral carotid plaques at age 78 years had an increased risk of stroke or mortality during the 5-year follow-up period (74% bilateral plaques versus 21% unilateral or no plaques). This was not found in the women (33% versus 26%). Carotid atherosclerosis was prevalent in a majority of elderly subjects. Bilateral plaques were correlated with systolic blood pressure and ischemic heart disease at age 70 years and predicted the risk of stroke and mortality in men but not in women.

Osteoporosis International, 2009

We evaluated the relation between serum FGF23 and bone mineral density (BMD) in a community-based... more We evaluated the relation between serum FGF23 and bone mineral density (BMD) in a community-based cohort of elderly men. There was a weak correlation between FGF23 and BMD, which was primarily dependent on body weight. Introduction FGF23 is a hormonal factor produced in bone and regulates serum levels of phosphate (Pi) and vitamin D. FGF23 over-expression is associated with skeletal abnormalities, including rickets/osteomalacia. The relation be-tween FGF23 and Bone Mineral Density (BMD) in the community remains unexplored. Methods We employed a large, population-based cohort of 3014 Swedish men aged 69-80 years, without known renal disease. BMD was measured with dual X-ray absorptiometry (DXA) in the hip and lumbar spine. Serum intact FGF23 was analyzed with a two-site monoclonal ELISA. Results There was a weak but significant correlation between FGF23 and BMD in femoral neck (r=0.04, p< 0.05), femoral trochanter (r=0.05, p=0.004), total hip (r= 0.06, p=0.0015) and lumbar spine (r=0.07, p=0.0004). The correlations remained significant when adjusting for biochemical covariates (Pi, calcium, PTH, 25(OH)D and renal function). However, the association became insignificant in all regions when adjusting for established con-Osteoporos Int (

Osteoporosis International, 2011

The association between bone mineral density (BMD) and myocardial infarction (MI) was investigate... more The association between bone mineral density (BMD) and myocardial infarction (MI) was investigated in 6,872 men and women. For both men and women, lower BMD in the femoral neck and hip was associated with increased risk of MI largely independent of smoking, hypertension, hypertriglyceridemia, and diabetes. Introduction The relationship between BMD and cardiovascular disease is not completely understood. The objective of this prospective study was to investigate the risk of MI in relation to bone mineral density and to determine if cardiovascular risk factors could explain this association. Methods Dual energy X-ray absorptiometry was performed in 5,490 women and 1,382 men to determine total hip and femoral neck BMD (in grams per square centimeters) and estimate femoral neck volumetric BMD (in grams per cubic centimeters). During a mean follow-up time of 5.7 years, 117 women and 79 men suffered an initial MI. Results After adjustment for age and BMI, lower BMD of the femoral neck and total hip was associated with increased risk of MI for both women [hazard ratio (HR)= 1.33, 95% confidence interval (CI) 1.08-1.66 per standard deviation (SD) decrease in femoral neck BMD] and men (HR=1.74, 95% CI 1.34-2.28 per SD decrease in total hip BMD). After additional adjustment for smoking, hypertension, hypertriglyceridemia, and diabetes, the associations were slightly attenuated in men (HR=1.42-1.88 in the age and BMI-adjusted model versus 1.33-1.77 in the fully adjusted model) while similar attenuations were seen in women (HR=1.06-1.25 versus 1.05-1.22). Conclusion Lower BMD was associated with an increase in MI risk for both men and women. Women had consistently lower HRs compared to men in all models. Adjusting for smoking, hypertension, hypertriglyceridemia, and diabetes did not distinctively weaken these associations.

Maturitas, 1993

The importance of reproductive and other health and social factors as predictors of bone mineral ... more The importance of reproductive and other health and social factors as predictors of bone mineral density (BMD) and fractures was investigated in a longitudinal study of 'IO-year-old women. At 70 years of age there was no correlation between menarcheal age, menopausal age, duration of fertile period and parity and BMD or a history of fractures. Bilateral oophorectomy (mean age at surgery 45.3 f 3.6 years) and the duration of tobacco smoking were negatively correlated to BMD at 70 years of age. Tobacco smoking was positively correlated to a history of fractures and body mass index (BMI) was negatively correlated to a history of fractures at 70 years of age. In a stepwise multiple regression model, height, body mass index and a history of hysterectomy were found to have a contributory, positively-correlated independent explanatory value for BMD at 70 years. In a logistic multiple regression analysis, bilateral oophorectomy was the only independent explanatory factor for fractures at 70 years of age. BMD was lower in women who had undergone bilateral oophorectomy compared with controls at 70 years of age. Hysterectomized women without bilateral oophorectomy showed a higher BMD in the right calcaneus at 70 years of age compared with controls. When comparing the reduction in bone mineral density between 70 and 76 years of age, the fifth quintile (women with the highest BMD) at 70 years of age decreased 2.7 times more (P < 0.01) than the first quintile. A longitudinal examination between 70 and 76 years revealed that BMD at the age of 70 was a significant (P < 0.01) predictor for fractures occurring between 70 and 76 years of age.

Journal of the American College of Cardiology, 2007

This study sought to determine whether serum levels of testosterone and estradiol associate with ... more This study sought to determine whether serum levels of testosterone and estradiol associate with lower extremity peripheral arterial disease (PAD) in a large population-based cohort of elderly men.

The Journal of Clinical Endocrinology & Metabolism, 2014

Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing T has been reg... more Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing T has been regarded as part of normal aging. However, the association between Hb and serum estradiol is incompletely known. To determine whether estradiol is associated with anemia/Hb and established determinants of Hb in elderly men without prostate cancer. The MrOS (Osteoporotic Fractures in Men) is a population-based study (n = 918; median age, 75.3 y; range, 70-81 y). We evaluated total estradiol in relation to Hb and adjusted for potential confounders (ie, age, body mass index [BMI], erythropoietin [EPO], total T, cystatin C, and iron and B-vitamin status). Estradiol correlated negatively with age (r = -0.14; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Hb correlated (age adjusted) positively with estradiol (r = 0.21; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and T (r = 0.10; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). Independent predictors for Hb in multivariate analyses were estradiol, EPO, BMI, transferrin saturation, cystatin C, and free T4, but not T. After exclusion of subjects with Hb &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;130 g/L and/or T…

The Journal of Clinical Endocrinology & Metabolism, 2007

Context: Androgens are associated with metabolic risk factors in men. However, the independent im... more Context: Androgens are associated with metabolic risk factors in men. However, the independent impact of androgens and androgen metabolites on metabolic risk factors in men is unclear.

Journal of Bone and Mineral Research, 2006

The role of androgens for bone health in elderly men is unclear. We show that free testosterone w... more The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men.

Journal of Bone and Mineral Research, 2011

Osteoporosis-related fractures constitute a major health concern not only in women but also in me... more Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Insulin-like growth factor 1 (IGF-1) is a key determinant of bone mass, but the association between serum IGF-1 and incident fractures in men remains unclear.

Journal of Bone and Mineral Research, 2008

Osteoporosis-related fractures constitute a major health concern not only in women but also in me... more Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n ‫ס‬ 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p < 0.001), but not fT, were independently associated with fracture risk. Further subanalyses of fracture type showed that fE2 was inversely associated with clinical vertebral fractures (HR per SD decrease, 1.57; 95% CI, 1.36-1.80), nonvertebral osteoporosis fractures (HR per SD decrease, 1.42; 95% CI, 1.23-1.65), and hip fractures (HR per SD decrease, 1.44; 95% CI, 1.18-1.76). The inverse relation between serum E2 and fracture risk was nonlinear with a strong relation <16 pg/ml for E2 and 0.3 pg/ml for fE2. In conclusion, older Swedish men with low serum E2 and high SHBG levels have an increased risk of fractures.

New England Journal of Medicine, 2001

Background Once-daily injections of parathyroid hormone or its amino-terminal fragments increase ... more Background Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown.

Journal of Urology, 2008

We assessed the factors significantly associated with lower urinary tract symptoms (LUTS) in men ... more We assessed the factors significantly associated with lower urinary tract symptoms (LUTS) in men with late-onset hypogonadism (LOH) syndrome. Methods: The study population consisted of 258 patients aged 40 years or older diagnosed with LOH syndrome. Each patient completed a questionnaire study, such as the International Index of Erectile Function (IIEF) 5, Aging Male Score (AMS), and International Prostate Symptom Score (IPSS). Body mass index (BMI), waist size, and muscle volume were measured in all patients, and blood biochemical data, including total cholesterol, triglyceride, hemoglobin A1c, and free testosterone (free T), were also collected. We analyzed the factors that have effect on IPSS. Results: The mean age of the patients was 64.9 ± 8.7 years, and the mean free T value was 7.3 ± 2.2 pg/mL. The critical factors affecting IPSS were IIEF5 score, BMI, muscle volume, age, AMS, and free T-value (P < 0.05). Age showed the strongest significant positive correlation with IPSS (r = 0.321, P < 0.001). Each factor was controlled for age. IIEF5 score and AMS were independent factors affecting IPSS (r = −0.221 and 0.195, respectively, P < 0.05). IPSS showed an inverse correlation with IIEF5, and a positive correlation with AMS. LUTS also had a weak negative correlation with Free T-value but this was not significant (r = −0.121, P = 0.061). Conclusion: Lower urinary tract symptoms were significantly correlated with erectile function and psychological symptoms in men with LOH syndrome.

The Journal of Urology, 2013

We tested the hypothesis that low vitamin D is associated with benign prostatic hyperplasia. We a... more We tested the hypothesis that low vitamin D is associated with benign prostatic hyperplasia. We also studied whether body composition, sex hormones, serum sex hormone-binding globulin, albumin corrected serum calcium, adiponectin and lipid status are associated with benign prostatic hyperplasia. We investigated 184 representative, randomly selected men 72 to 76 years old enrolled in the Gothenburg arm of the Osteoporotic Fractures in Men Study (MrOS). Men with a history of prostate cancer, prostate operation or medication for benign prostatic hyperplasia were excluded from study, leaving 155 available for analysis. A cross-sectional study was performed in which benign prostatic hyperplasia measured by total prostate volume was related to clinical, anthropometric, endocrine and metabolic factors on univariate and multivariate analyses with regression models. Median prostate volume was 40 ml. In multivariate models only 25-OH vitamin D, albumin corrected serum calcium, serum sex hormone-binding globulin and high density lipoprotein cholesterol were significantly and inversely associated with large prostate glands. The current report adds 4 independent factors associated with benign prostatic hyperplasia, including low 25-OH vitamin D, serum calcium, sex hormone-binding globulin and high density lipoprotein cholesterol.

Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT)2B15 and UG... more Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT)2B15 and UGT2B17 glucuronidate androgens and their metabolites.

Journal of Clinical Densitometry, 2014

Cortical porosity increases with age and affects bone strength, but its association with fracture... more Cortical porosity increases with age and affects bone strength, but its association with fracture in older men is unknown. The aim of this study was to investigate whether cortical porosity is associated with prevalent fractures in older men. A subsample of 456 men aged 80.2 ± 3.5 (mean ± SD) years, with available high resolution peripheral quantitative computed tomography measurements at the tibia from the 5-year follow up exam, was drawn from the prospective MrOS Gothenburg study. Dual-energy x-ray absorptiometry was used to measure areal bone mineral density (aBMD). Data on physical activity, calcium intake, medications, diseases, and smoking were collected on questionnaires at the follow-up exam. Of 87 men (19.1%) with fracture at or after age 50 (all fracture group), 52 (11.4%) had had a self-reported fracture before the baseline exam and 35 (7.7%) had had an x-ray verified fracture between baseline and follow-up. Men in the all-fracture group and in the x-ray verified group had 15.8% (13.2 ± 4.9 vs.11.4 ± 3.8%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and 21.6% (14.1 ± 5.2 vs.11.6 ± 3.9%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) higher cortical porosity, respectively, than men in the non-fracture group. The independent associations between bone microstructure parameters and fracture were tested using multivariate logistic regression with age, height, weight, calcium intake, smoking, physical activity, medications, and diseases as covariates. Cortical porosity was independently associated with any fracture (reported or x-ray verified; OR per SD increase: 1.49; 95% confidence interval (CI): 1.17-1.90) and with any x-ray verified fracture alone (OR: 1.73; 95% CI: 1.23-2.42). Including aBMD (spine or hip, respectively) in the multivariate logistic regression above revealed that cortical porosity was associated with any fracture (OR: 1.54; 95% CI: 1.17-2.01) and with x-ray verified fracture alone (OR: 1.49; 95% CI: 1.00-2.22). Cortical porosity was associated with prevalence of fracture even after adjustment for aBMD. This article is protected by copyright. All rights reserved.

PLOS Genetics, 2014

Variation in plasma levels of cortisol, an essential hormone in the stress response, is associate... more Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that ,1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding a1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

The Spine Journal, 2015

The epidemiology, the fracture pattern, and the clinical relevance of prevalent vertebral fractur... more The epidemiology, the fracture pattern, and the clinical relevance of prevalent vertebral fractures in old men are debated wherefore we set out to clarify these issues. Mister Osteoporosis (MrOs) Sweden is a population-based cohort of community-living men aged 69-81 years that includes 3,014 men. Out of these, 1,453 men underwent a lateral radiograph of the thoracic and lumbar spine of which 1,427 were readable and classified by a radiologist, that is the sample size in this study. The men also answered a questionnaire evaluating back pain and limitation in activities of daily living (ADLs) because of back pain during the preceding 12 months in addition with fracture history and life style. Fifteen percentage of the men had at least one prevalent vertebral fracture, but only 1/10th of these were aware of their fracture. Among the men with a fracture, 58% had one, 21% two, 9% three, and 11% four or more fractures. In men with only one fracture, 70% of the fractures were located in the thoracic and 30% in the lumbar spine, 85% had a wedge, 13% a biconcave, and 2% a crush-type configuration; one-quarter had a maximum vertebral body compression degree of less than 24% and one-quarter of more than 38%. Among the men with one or several vertebral fracture, 57% reported back pain compared with 55% in those without a fracture (p=.53). Most ADL functions were similar in the men with or without a prevalent vertebral fracture. In the men with one fracture, there was no difference in the occurrence of back pain depending on the fractured region (p=.49), type of the fracture (p=.77), or degree of compression (p=.85). In men with one or several fractures, there were no significant differences in the presence of back pain in any ages (p=.08), nor there were differences in presence of back pain regarding type (p=.08) or number of fractures (p=.21). A prevalent vertebral fracture is common in old men but has low clinical relevance. There does not seem to be a specific fracture pattern that predisposes for back pain.

The lancet. Diabetes & endocrinology, 2014

Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pre... more Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blo...

Journal of the American College of Cardiology, 2014

The adrenal sex hormone dehydroepiandrosterone (DHEA), which is present in serum mainly as the su... more The adrenal sex hormone dehydroepiandrosterone (DHEA), which is present in serum mainly as the sulfate DHEA-S, is the most abundant steroid hormone in human blood. Its levels decline dramatically with age. Despite the great amount of literature on vascular and metabolic actions of DHEA/-S, evidence for an association between DHEA/-S levels and cardiovascular events is contradictory. This study tested the hypothesis that serum DHEA and DHEA-S are predictors of major coronary heart disease (CHD) and/or cerebrovascular disease (CBD) events in a large cohort of elderly men. We used gas and liquid chromatography-mass spectrometry to analyze baseline levels of DHEA and DHEA-S in the prospective population-based Osteoporotic Fractures in Men study in Sweden (2,416 men, ages 69 to 81 years). Complete cardiovascular clinical outcomes were available from national Swedish registers. During the 5-year follow-up, 302 participants experienced a CHD event, and 225 had a CBD event. Both DHEA and DHEA-S levels were inversely associated with the age-adjusted risk of a CHD event; the hazard ratios and 95% confidence intervals per SD increase were 0.82 (0.73 to 0.93) and 0.86 (0.77 to 0.97), respectively. In contrast, DHEA/-S showed no statistically significant association with the risk of CBD events. The association between DHEA and CHD risk remained significant after adjustment for traditional cardiovascular risk factors, serum total testosterone and estradiol, C-reactive protein, and renal function, and remained unchanged after exclusion of the first 2.6 years of follow-up to reduce reverse causality. Low serum levels of DHEA and its sulfate predict an increased risk of CHD, but not CBD, events in elderly men.

Journal of Internal Medicine, 2014

Blood haemoglobin (Hb) concentration declines in elderly men, whilst the level of the adipocyte-d... more Blood haemoglobin (Hb) concentration declines in elderly men, whilst the level of the adipocyte-derived protein adiponectin increases with age. The association between erythropoiesis and adiponectin in elderly men is unclear. The aim of this study was to determine whether adipokines such as adiponectin and leptin are associated with anaemia and Hb concentration in elderly community-dwelling men. The Gothenburg part of the population-based Swedish Osteoporotic Fractures in Men (MrOS) cohort (n = 1010; median age 75.3 years, range 69-81). We investigated the associations between levels of adiponectin and Hb before and after adjusting for potential confounders [i.e. age, body composition, erythropoietin (EPO), total oestradiol, leptin, cystatin C and iron and B vitamin status]. In these elderly men, age was negatively associated with Hb (r = -0.12, P &amp;amp;amp;amp;lt; 0.001) and positively associated with adiponectin level (r = 0.13, P &amp;amp;amp;amp;lt; 0.001). In age-adjusted partial correlations, Hb and adiponectin levels were negatively correlated (r = -0.20, P &amp;amp;amp;amp;lt; 0.001); this association remained significant after multivariable adjustment for age, body composition, EPO, fasting insulin, sex hormones, leptin and ferritin. Age-adjusted mean adiponectin concentrations were significantly higher in anaemic men (66/1005; Hb &amp;amp;amp;amp;lt;130 g L(-1) ) compared to nonanaemic men (14.0 vs. 11.7 μg mL(-1) , P &amp;amp;amp;amp;lt; 0.05). In multivariate analysis, adiponectin together with EPO, total oestradiol, insulin, albumin, transferrin saturation, HDL cholesterol, cystatin C, total body fat mass and free thyroxine, but not leptin, explained 35% of the variation in Hb level. These results remained essentially unchanged after exclusion of men with diabetes. Serum adiponectin, but not leptin, was negatively and independently associated with Hb. This finding suggests a possible role of adiponectin in the age-related decline in Hb level observed in apparently healthy elderly men.

Stroke, 2002

The aim of this study was to assess the relationship between cardiovascular risk factors, atheros... more The aim of this study was to assess the relationship between cardiovascular risk factors, atherosclerotic disease in the carotid bifurcation, and the risk of stroke and mortality in a representative population sample. One hundred forty-two men and women participated in a population study at ages 70 and 76 years. At age 78, extracranial and intracranial circulation was examined by means of duplex sonography and transcranial Doppler techniques. Mortality and hospitalization for stroke were analyzed over a 5-year follow-up period up to age 83 years. Carotid plaques were identified in 82% of the men and 79% of the women. Bilateral plaques were found in 57% of the men and 46% of the women, and stenosis resulting in &gt;50% diameter reduction occurred in 28% of the men and 17% of the women. Carotid stenosis &gt;75% was observed in 7 subjects (0.5%). Bilateral plaques at age 78 were correlated with systolic blood pressure and ischemic heart disease at age 70 years. The pulsatility index was 1.0 to 1.4 in 63% and &gt; or =1.5 in 13% of the study population. The pulsatility index was correlated with systolic and diastolic blood pressure, serum cholesterol, and triglycerides. Men with bilateral carotid plaques at age 78 years had an increased risk of stroke or mortality during the 5-year follow-up period (74% bilateral plaques versus 21% unilateral or no plaques). This was not found in the women (33% versus 26%). Carotid atherosclerosis was prevalent in a majority of elderly subjects. Bilateral plaques were correlated with systolic blood pressure and ischemic heart disease at age 70 years and predicted the risk of stroke and mortality in men but not in women.

Osteoporosis International, 2009

We evaluated the relation between serum FGF23 and bone mineral density (BMD) in a community-based... more We evaluated the relation between serum FGF23 and bone mineral density (BMD) in a community-based cohort of elderly men. There was a weak correlation between FGF23 and BMD, which was primarily dependent on body weight. Introduction FGF23 is a hormonal factor produced in bone and regulates serum levels of phosphate (Pi) and vitamin D. FGF23 over-expression is associated with skeletal abnormalities, including rickets/osteomalacia. The relation be-tween FGF23 and Bone Mineral Density (BMD) in the community remains unexplored. Methods We employed a large, population-based cohort of 3014 Swedish men aged 69-80 years, without known renal disease. BMD was measured with dual X-ray absorptiometry (DXA) in the hip and lumbar spine. Serum intact FGF23 was analyzed with a two-site monoclonal ELISA. Results There was a weak but significant correlation between FGF23 and BMD in femoral neck (r=0.04, p< 0.05), femoral trochanter (r=0.05, p=0.004), total hip (r= 0.06, p=0.0015) and lumbar spine (r=0.07, p=0.0004). The correlations remained significant when adjusting for biochemical covariates (Pi, calcium, PTH, 25(OH)D and renal function). However, the association became insignificant in all regions when adjusting for established con-Osteoporos Int (

Osteoporosis International, 2011

The association between bone mineral density (BMD) and myocardial infarction (MI) was investigate... more The association between bone mineral density (BMD) and myocardial infarction (MI) was investigated in 6,872 men and women. For both men and women, lower BMD in the femoral neck and hip was associated with increased risk of MI largely independent of smoking, hypertension, hypertriglyceridemia, and diabetes. Introduction The relationship between BMD and cardiovascular disease is not completely understood. The objective of this prospective study was to investigate the risk of MI in relation to bone mineral density and to determine if cardiovascular risk factors could explain this association. Methods Dual energy X-ray absorptiometry was performed in 5,490 women and 1,382 men to determine total hip and femoral neck BMD (in grams per square centimeters) and estimate femoral neck volumetric BMD (in grams per cubic centimeters). During a mean follow-up time of 5.7 years, 117 women and 79 men suffered an initial MI. Results After adjustment for age and BMI, lower BMD of the femoral neck and total hip was associated with increased risk of MI for both women [hazard ratio (HR)= 1.33, 95% confidence interval (CI) 1.08-1.66 per standard deviation (SD) decrease in femoral neck BMD] and men (HR=1.74, 95% CI 1.34-2.28 per SD decrease in total hip BMD). After additional adjustment for smoking, hypertension, hypertriglyceridemia, and diabetes, the associations were slightly attenuated in men (HR=1.42-1.88 in the age and BMI-adjusted model versus 1.33-1.77 in the fully adjusted model) while similar attenuations were seen in women (HR=1.06-1.25 versus 1.05-1.22). Conclusion Lower BMD was associated with an increase in MI risk for both men and women. Women had consistently lower HRs compared to men in all models. Adjusting for smoking, hypertension, hypertriglyceridemia, and diabetes did not distinctively weaken these associations.

Maturitas, 1993

The importance of reproductive and other health and social factors as predictors of bone mineral ... more The importance of reproductive and other health and social factors as predictors of bone mineral density (BMD) and fractures was investigated in a longitudinal study of 'IO-year-old women. At 70 years of age there was no correlation between menarcheal age, menopausal age, duration of fertile period and parity and BMD or a history of fractures. Bilateral oophorectomy (mean age at surgery 45.3 f 3.6 years) and the duration of tobacco smoking were negatively correlated to BMD at 70 years of age. Tobacco smoking was positively correlated to a history of fractures and body mass index (BMI) was negatively correlated to a history of fractures at 70 years of age. In a stepwise multiple regression model, height, body mass index and a history of hysterectomy were found to have a contributory, positively-correlated independent explanatory value for BMD at 70 years. In a logistic multiple regression analysis, bilateral oophorectomy was the only independent explanatory factor for fractures at 70 years of age. BMD was lower in women who had undergone bilateral oophorectomy compared with controls at 70 years of age. Hysterectomized women without bilateral oophorectomy showed a higher BMD in the right calcaneus at 70 years of age compared with controls. When comparing the reduction in bone mineral density between 70 and 76 years of age, the fifth quintile (women with the highest BMD) at 70 years of age decreased 2.7 times more (P < 0.01) than the first quintile. A longitudinal examination between 70 and 76 years revealed that BMD at the age of 70 was a significant (P < 0.01) predictor for fractures occurring between 70 and 76 years of age.

Journal of the American College of Cardiology, 2007

This study sought to determine whether serum levels of testosterone and estradiol associate with ... more This study sought to determine whether serum levels of testosterone and estradiol associate with lower extremity peripheral arterial disease (PAD) in a large population-based cohort of elderly men.

The Journal of Clinical Endocrinology & Metabolism, 2014

Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing T has been reg... more Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing T has been regarded as part of normal aging. However, the association between Hb and serum estradiol is incompletely known. To determine whether estradiol is associated with anemia/Hb and established determinants of Hb in elderly men without prostate cancer. The MrOS (Osteoporotic Fractures in Men) is a population-based study (n = 918; median age, 75.3 y; range, 70-81 y). We evaluated total estradiol in relation to Hb and adjusted for potential confounders (ie, age, body mass index [BMI], erythropoietin [EPO], total T, cystatin C, and iron and B-vitamin status). Estradiol correlated negatively with age (r = -0.14; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Hb correlated (age adjusted) positively with estradiol (r = 0.21; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and T (r = 0.10; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). Independent predictors for Hb in multivariate analyses were estradiol, EPO, BMI, transferrin saturation, cystatin C, and free T4, but not T. After exclusion of subjects with Hb &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;130 g/L and/or T…

The Journal of Clinical Endocrinology & Metabolism, 2007

Context: Androgens are associated with metabolic risk factors in men. However, the independent im... more Context: Androgens are associated with metabolic risk factors in men. However, the independent impact of androgens and androgen metabolites on metabolic risk factors in men is unclear.

Journal of Bone and Mineral Research, 2006

The role of androgens for bone health in elderly men is unclear. We show that free testosterone w... more The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men.

Journal of Bone and Mineral Research, 2011

Osteoporosis-related fractures constitute a major health concern not only in women but also in me... more Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Insulin-like growth factor 1 (IGF-1) is a key determinant of bone mass, but the association between serum IGF-1 and incident fractures in men remains unclear.

Journal of Bone and Mineral Research, 2008

Osteoporosis-related fractures constitute a major health concern not only in women but also in me... more Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n ‫ס‬ 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p < 0.001), but not fT, were independently associated with fracture risk. Further subanalyses of fracture type showed that fE2 was inversely associated with clinical vertebral fractures (HR per SD decrease, 1.57; 95% CI, 1.36-1.80), nonvertebral osteoporosis fractures (HR per SD decrease, 1.42; 95% CI, 1.23-1.65), and hip fractures (HR per SD decrease, 1.44; 95% CI, 1.18-1.76). The inverse relation between serum E2 and fracture risk was nonlinear with a strong relation <16 pg/ml for E2 and 0.3 pg/ml for fE2. In conclusion, older Swedish men with low serum E2 and high SHBG levels have an increased risk of fractures.