Dan Mellström

Sahlgrenska University Hospital, Goeteborg, Västra Götaland, Sweden

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Publications (270)1171.55 Total impact

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    Full-text · Article · Dec 2015 · Osteoporosis International
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    ABSTRACT: Reference point indentation is a novel method to assess bone material strength index (BMSi) in vivo. We found that BMSi at the mid-tibia was weakly associated with spine and hip areal bone mineral density but not with prevalent fracture in a population-based cohort of 211 older women. Introduction Reference point indentation is a novel method to assess BMSi in vivo. Lower BMSi has been observed in patients with prior fracture than in controls, but no association between BMSi and areal bone mineral density (aBMD) has been found. Population-based association studies and prospective studies with BMSi and fractures are lacking. We hypothesized that BMSi would be associated with prevalent fractures in older Swedish women. The aim was to investigate the associations between BMSi, aBMD, and prevalent fracture in older women. Methods Two hundred eleven women, mean age 78.3 ± 1.1 years, were included in this cross-sectional, population-based study. BMSi was assessed using the OsteoProbe device at the mid-tibia. Areal BMD of the hip, spine, and non-dominant radius was measured using dual-energy X-ray absorptiometry (DXA). Fracture history was retrieved using questionnaires, and vertebral fractures were identified using vertebral fracture assessment (VFA) by DXA. Results One hundred ninety-eight previous fractures in 109 subjects were reported. A total of 106 women had a vertebral fracture, of which 58 women had moderate or severe fractures. An inverse correlation between BMSi and weight (r = −0.14, p = 0.04) was seen, and BMSi differed according to operator (ANOVA p < 0.01). Adjusting for weight and operator in a linear regression model, we found that BMSi was positively associated with aBMD of the total hip (β = 0.14, p = 0.04), non-dominant radius (β = 0.17, p = 0.02), and lumbar spine (L1–L4) (β = 0.14, p < 0.05). Using logistic regression, we could not find any association in crude or adjusted BMSi (for age, weight, height, walking speed, calcium intake, smoking, bisphosphonate and glucocorticoid use, and operator) with prevalent fractures. Conclusion We conclude that BMSi is associated with aBMD but not with prevalent fracture in a population-based cohort of 211 older women.
    No preview · Article · Dec 2015 · Osteoporosis International
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    ABSTRACT: One risk factor for osteoporosis which has attracted increasing attention in recent years is exposure to cadmium. The aim of this study was to examine the associations between low-level cadmium exposure, from diet and smoking, and BMD and incident fractures in elderly men. The study population consisted of 936 men from the Swedish cohort of the MrOS study, aged 70-81 years at inclusion (year 2002-2004), with reliable data on cadmium in urine (U-Cd) analyzed using inductively coupled plasma mass spectrometry in baseline samples. The participants also answered a questionnaire on lifestyle factors and medical history. BMD was measured at baseline using DXA in the total body, hip, and lumbar spine. During the follow-up period (until 2013), all new fractures were registered by date and type. Associations between BMD and U-Cd were assessed using multiple linear regression, and associations between incident fractures and baseline U-Cd were analyzed using Cox regression. In both cases, a number of potential confounders and other risk factors (e.g. age, smoking, BMI, and physical activity) were included in the models. We found significant negative associations between U-Cd and BMD, with lower BMD (4-8%) for all sites in the fourth quartile of U-Cd, using the first quartile as the reference. In addition, we found positive associations between U-Cd and incident fractures, especially non-vertebral osteoporosis fractures in the fourth quartile of U-Cd, with hazard ratios of 1.8-3.3 in the various models. U-Cd as a continuous variable was significantly associated with non-vertebral osteoporosis fractures (adjusted hazard ratio 1.3-1.4 per µg Cd/g creatinine), also in never-smokers, but not with the other fracture groups (all fractures, hip fractures, vertebral fractures, and other fractures). Our results indicate that even relatively low cadmium exposure through diet and smoking increases the risk of low BMD and osteoporosis-related fractures in elderly men. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.
    Full-text · Article · Oct 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: Objective: Studies of the association between circulating IGF-I and cancer risk have shown conflicting results. We have previously observed a U-shaped association between IGF-I and cancer mortality. The present study test the hypotheses of a U-shaped association between IGF-I and incident cancer. Design: Elderly men (2368), randomly recruited from the general community. Methods: IGF-I was measured in a cohort of elderly men. Complete data for incident cancer was obtained from the Swedish Cancer Registry. Statistical analyses included Cox proportional hazards regressions with or without a spline approach. Results: 369 participants had incident cancer after baseline. Prostate cancer was most frequent (n=140). There was no association between serum IGF-I and all cancer or prostate cancer incidence. However, there was a nonlinear association between IGF-I and non-prostate cancer incidence (p = <0.05). Exploratory analyses were performed for low and high serum IGF-I (quintiles 1 and 5) vs. intermediate (quintiles 2-4, referent). There was a tendency of increased non-prostate cancer risk in men with high IGF-I (HR = 1.26, 95% confidence interval (CI): 0.92-1.71, p=0.15). After excluding participants with follow-up of less than 2.6 years (half median follow-up time), to control for potential diagnostic delay, the association was statistically significant (HR = 1.55, CI: 1.03-2.35). Conclusion: There was a significant nonlinear association between IGF-I and non-prostate cancer. No association between IGF-I and prostate cancer was observed. Future studies are warranted to further investigate this nonlinear association, including whether IGF-I concentration is a reproducible, and useful, risk marker of non-prostate cancer. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2015 · Clinical Endocrinology
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    ABSTRACT: Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone-binding globulin (SHBG) associate with non-vertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the MrOS study had baseline estradiol and testosterone analyzed by GC-MS and SHBG by IRMA. Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow-up of 9.1 years. In a subsample of these men (n = 2256), spine X-rays were obtained at baseline and after an average follow-up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (HR per SD increase, 95% CI: 0.93, 0.80-1.08) nor testosterone (1.05, 0.91-1.21) predicted incident clinical vertebral fractures in age-adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12-1.37). This association remained significant after further adjustment for FRAX® with or without BMD. SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; OR per SD increase, 95% CI: 1.23, 1.05-1.44). This association remained significant after adjustment for FRAX® with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX® with BMD for vertebral fracture risk prediction. This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: Falls and fractures share several common risk factors. Although past falls is not included as an input variable in the FRAX calculator, we demonstrate that FRAX probability predicts risk of incident falls in the MrOs Sweden cohort. Introduction: Although not included in the FRAX® algorithm, it is possible that increased falls risk is partly dependent on other risk factors that are incorporated into FRAX. The aim of the present study was to determine whether fracture probability generated by FRAX might also predict risk of incident falls and the extent that a falls history would add value to FRAX. Methods: We studied the relationship between FRAX probabilities and risk of falls in 1836 elderly men recruited to the MrOS study, a population-based prospective cohort of men from Sweden. Baseline data included falls history, clinical risk factors, bone mineral density (BMD) at femoral neck, and calculated FRAX probabilities. Incident falls were captured during an average of 1.8 years of follow-up. An extension of Poisson regression was used to investigate the relationship between FRAX, other risk variables, and the time-to-event hazard function of falls. All associations were adjusted for age and time since baseline. Results: At enrolment, 15.5 % of the men had fallen during the preceding 12 months (past falls) and 39 % experienced one or more falls during follow-up (incident falls). The risk of incident falls increased with increasing FRAX probabilities at baseline (hazard ratio (HR) per standard deviation (SD), 1.16; 95 % confidence interval (95%CI), 1.06 to 1.26). The association between incident falls and FRAX probability remained after adjustment for past falls (HR per SD, 1.12; 95%CI, 1.03 to 1.22). High compared with low baseline FRAX score (>15 vs <15 % probability of major osteoporotic fracture) was strongly predictive of increased falls risk (HR, 1.64; 95%CI, 1.36 to 1.97) and remained stable with time. Whereas past falls were a significant predictor of incident falls (HR, 2.75; 95%CI, 2.32 to 3.25), even after adjustment for FRAX, the hazard ratio decreased markedly with increasing follow-up time. Conclusions: Although falls are not included as an input variable, FRAX captures a component of risk for future falls and outperforms falls history with an extended follow-up time. © 2015 International Osteoporosis Foundation and National Osteoporosis Foundation
    No preview · Article · Sep 2015 · Osteoporosis International
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    ABSTRACT: We sought to determine whether specific characteristics of vertebral fractures in elderly men are associated with low bone mineral density (BMD) and osteoporosis. Mister osteoporosis Sweden is a population based cohort study involving 3014 men aged 69 to 81 years. Of these, 1427 had readable lateral radiographs of the thoracic and lumbar spine. Total body (TB) BMD (g/cm²) and total right hip (TH) BMD were measured by dual energy x-ray absorptiometry. The proportion of men with osteoporosis was calculated from TH BMD. There were 215 men (15.1%) with a vertebral fracture. Those with a fracture had lower TB BMD than those without (p < 0.001). Among men with a fracture, TB BMD was lower in those with more than three fractures (p = 0.02), those with biconcave fractures (p = 0.02) and those with vertebral body compression of > 42% (worst quartile) (p = 0.03). The mean odds ratio (OR) for having osteoporosis when having any type of vertebral fracture was 6.1 (95% confidence interval (CI) 3.9 to 9.5) compared with those without a fracture. A combination of more than three fractures and compression in the worst quartile had a mean OR of 114.2 (95% CI 6.7 to 1938.3) of having osteoporosis compared with those without a fracture. We recommend BMD studies to be undertaken in these subcohorts of elderly men with a vertebral fracture. Cite this article: 2015;97-B:1106-10. ©2015 The British Editorial Society of Bone & Joint Surgery.
    No preview · Article · Aug 2015 · Bone and Joint Journal
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    ABSTRACT: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS-EU) was designed to better understand the rate and burden of gastrointestinal (GI) events on clinical and health care outcomes among postmenopausal women with osteoporosis. MUSIC OS-EU is a prospective, multinational, observational cohort study of postmenopausal women ≥50 years of age diagnosed with osteoporosis and enrolled in physician clinics in six countries: France, Italy, the Netherlands, Sweden, the United Kingdom, and Canada. The MUSIC OS-EU study has three components: (i) a physician survey to describe their management of osteoporotic patients with GI events; (ii) a retrospective chart survey to describe the receipt and type of osteoporosis medication prescribed; and (iii) a prospective cohort study including untreated and treated patients diagnosed with osteoporosis to investigate the rate of GI events and association with osteoporosis medication use patterns, health-related quality of life, treatment satisfaction and resource utilisation among postmenopausal women with osteoporosis. Physicians at 97 sites completed the physician questionnaire and data for 716 patients were abstracted for the retrospective chart review. Enrolment and the baseline data collection for the prospective cohort study were conducted between March 2012 and June 2013 for 292 untreated and 2,959 treated patients, of whom 684 were new users and 2,275 were experienced users of oral osteoporosis medications. The results of MUSIC OS-EU will illuminate the association of GI events with the management of osteoporosis and with patient-reported outcomes among postmenopausal women with osteoporosis in Europe and Canada.
    No preview · Article · Jul 2015 · Clinical and experimental rheumatology
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    ABSTRACT: Background Denosumab treatment was shown to decrease the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis in the 3-year FREEDOM trial. The 7-year FREEDOM Extension is an open-label study to evaluate the long-term safety and efficacy of denosumab treatment for up to 10 years. Objectives To report the results through year 6 of the FREEDOM open-label Extension, representing up to 9 years of continued denosumab for the treatment of postmenopausal osteoporosis. Methods During the Extension, all women received 60 mg denosumab every 6 months, and daily calcium and vitamin D. At Extension year 6, bone turnover markers, nonvertebral fracture incidence, and adverse events were evaluated. In these analyses, women in the long-term group received up to 9 years of denosumab (3 years in FREEDOM and up to 6 years in the Extension); women in the cross-over group received up to 6 years of denosumab (3 years of placebo in FREEDOM and up to 6 years of denosumab in the Extension), allowing replication of results from the long-term group. Results Of the women who enrolled in the Extension, 3,098 (68%) were still on study at the beginning of year 6, with a mean age of 79 years (range 68–98 years). In both groups, serum CTx and P1NP were similarly reduced after each denosumab dose. The characteristic attenuation was observed through each dosing period and reductions were sustained through Extension year 6. The yearly incidences of nonvertebral (Figure) and major nonvertebral fractures remained low in both groups. Rates of adverse events and serious adverse events were consistent with previously reported Extension data. In Extension year 6, 2 events were adjudicated positive for ONJ in the cross-over group; there were no cases of atypical femoral fracture in either group. Conclusions In this aging population, denosumab treatment for up to 9 years maintained reduced bone turnover and was associated with continued low incidence of nonvertebral and major nonvertebral fractures. The benefit/risk profile remained favorable. Disclosure of Interest S. Papapoulos Consultant for: Amgen Inc., Axsome, Gador, GSK, Merck, Novartis, UCB, C. Roux Grant/research support from: Bongrain, Lilly, MSD, Consultant for: Amgen Inc., MSD, H. G. Bone Grant/research support from: Amgen Inc., Merck, Novartis, Consultant for: Amgen Inc., Merck, Mission, Novartis, P. Dakin Shareholder of: Amgen Inc., Employee of: Amgen Inc., E. Czerwiński Grant/research support from: Amgen Inc., D. Frey Grant/research support from: Abbot, Amgen Inc., Daiichi-Sankyo, Lilly, Novartis, UCB, Consultant for: Amgen Inc., Meda, Takeda, D. Kendler Grant/research support from: Amgen Inc., Astalis, Astra Zeneca, Eli Lilly, GSK, Novartis, Consultant for: Amgen Inc., Eli Lilly, GSK, Merck, Pfizer, Speakers bureau: Amgen Inc., Eli Lilly, Novartis, E. M. Lewiecki Grant/research support from: Amgen Inc., Lilly, Merck, Consultant for: AgNovos, Alexion, Amgen Inc., Lilly, Merck, NPS, Radius Health, J. Malouf: None declared, D. Mellström: None declared, J. Y. Reginster Grant/research support from: Amgen Inc., Bristol Myers Squibb, GlaxoSmithKline, Lilly, Merck Sharp & Dohme, Novartis, Roche, Rottapharm, Servier, Teva, Consultant for: Amgen Inc., GlaxoSmithKline, Lilly, Merckle, Negma, Novartis, NPS, Nycomed, Roche, Servier, Theramex, UCB, Wyeth, H. Resch Grant/research support from: Amgen Inc., Lilly, Consultant for: Amgen Inc., Lilly, MSD, Speakers bureau: Amgen Inc., Lilly, MSD, UCB, N. S. Daizadeh Shareholder of: Amgen Inc., Employee of: Amgen Inc., A. Wang Shareholder of: Amgen Inc., Employee of: Amgen Inc., M. Gavin Shareholder of: Amgen Inc., Employee of: Amgen Inc., R. B. Wagman Shareholder of: Amgen Inc., Employee of: Amgen Inc., M. L. Brandi Grant/research support from: Abiogen, Alexion, Amgen Inc., Bruno Farmaceutici, Eli Lilly, MSD, NPS, Servier, Shire, SPA, Consultant for: Abiogen, Alexion, Amgen Inc., MSD, NPS, Servier, Shire, SPA
    No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: The incidence of hip fracture in Sweden is substantially lower in immigrants than in the population born in Sweden. Thus, the use of a FRAX® model in immigrants overestimates the risk of fracture, and the use of country of origin-specific models may be more appropriate. Age-specific fracture and mortality rates vary between countries so that FRAX tools are country-specific. In the case of immigrants, it is not known whether the model for the original or the new country is most appropriate. The aim of this study was to compare the incidence of hip fractures in foreign-born and Swedish-born individuals residing in Sweden. We studied the incidence of hip fracture in all men and women aged 50 years or more in Sweden between 1987 and 2002. The population comprised 2.8 million Swedish-born and 270,000 foreign-born individuals. Incident hip fractures occurred in 239,842 Swedish-born and 12,563 foreign-born individuals. The hip fracture incidence rose with age for both groups and was higher for women than men amongst both Swedish-born and foreign-born individuals. The hip fracture incidence for the Swedish-born cohort was approximately twice that of immigrants. For example, at the age of 70 years, the annual hip fracture incidence (per 100,000) was 450 (95 % CI 446-454) for a Swedish-born woman and 239 (95 % CI 223-257) for a foreign-born woman at the time of immigration. The hip fracture incidence rose slowly with time from immigration (0.6 % per annum, 95 % CI 0.5-0.8 %) but remained significantly lower than for Swedish-born individuals even after 40 years of residence. The incidence of hip fracture in Sweden is substantially lower in immigrants than in the population native to Sweden. Although there was a small rise in age- and sex-specific incidence after immigration, the incidence remained markedly lower than that observed in Swedish-born individuals. Thus, the use of a FRAX model for Sweden will overestimate the risk of fracture for foreign-born individuals living in Sweden.
    No preview · Article · May 2015 · Osteoporosis International
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    ABSTRACT: Context: Peak bone mass is an important factor for the lifetime risk of developing osteoporosis. Ways to predict bone development in young adulthood are lacking. Objective and Main Outcome Measures: The aim of this study was to investigate whether baseline measurements of bone turnover markers could predict bone development in early adulthood in men. Design, setting, and participants: In total, 817 men (age at baseline, 18.9 ± 0.6 y; mean ± SD) from the population-based Gothenburg Osteoporosis and Obesity Determinants Study were included in this 5-year longitudinal study. Areal bone mineral density (aBMD) and bone mineral content (BMC) were measured using dual-energy x-ray absorptiometry, and volumetric BMD (vBMD) and cortical bone size were measured using peripheral quantitative computed tomography. Blood samples were collected at the baseline visit, and levels of osteocalcin (OC) and N-terminal telopeptide of type I collagen were analyzed. Results: OC was a positive predictor of the increase in aBMD and BMC of the total body (R(2): aBMD, 6.6%; BMC, 4.9%), lumbar spine (R(2): aBMD, 5.4%; BMC, 5.7%), and radius (R(2): aBMD, 14.8%; BMC, 12.8%) between 19 and 24 years (P < .001). Men in the highest OC quartile at baseline (35.2 ± 4.4 ng/mL; mean ± SD) gained markedly more in radius cortical cross-sectional area (4.0 ± 4.3 vs 1.9 ± 2.9 mm(2)) and trabecular vBMD (11 ± 7 vs 3 ± 12 mg/mm(3)) than men in the lowest OC quartile at baseline (17.7 ± 2.3 ng/mL; mean ± SD) (P < .001). Conclusion: A high OC level at the age of 19 predicts a favorable development in BMD, BMC, and bone size between 19 and 24 years of age.
    No preview · Article · Jan 2015 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: ContextIt is important to identify the patients at highest risk of fractures. A recent large-scale meta-analysis identified 63 autosomal SNPs associated with bone mineral density (BMD), of which 16 were also associated with fracture risk. Based on these findings two genetic risk scores (GRS63 and GRS16) were developed.Objective To determine the clinical usefulness of these GRS for the prediction of BMD, BMD change and fracture risk in elderly subjects.Design, Settings and ParticipantsTwo male (MrOS US, MrOS Sweden) and one female (SOF) large prospective cohorts of older subjects.Main Outcome MeasuresBMD, BMD change and radiographically and/or medically confirmed incident fractures (8,067 subjects, 2,185 incident non-vertebral or vertebral fractures).ResultsGRS63 was associated with BMD (≅3% of the variation explained), but not with BMD change.Both GRS63 and GRS16 were associated with fractures. After BMD-adjustment, the effect sizes for these associations were substantially reduced.Similar results were found using an unweighted GRS63 and an unweighted GRS16 compared to those found using the corresponding weighted risk scores.Only minor improvements in C-statistics (AUC) for fractures were seen when the GRSs were added to a base model (age, weight and height) and no significant improvements in C-statistics were seen when they were added to a model further adjusted for BMD. Net reclassification improvements with the addition of the GRSs to a base model were modest and substantially attenuated in BMD-adjusted models.Conclusions and RelevanceGRS63 is associated with BMD, but not BMD change, suggesting that the genetic determinants of BMD differ from those of BMD change. When BMD is known, the clinical utility of the two GRSs for fracture prediction is limited in elderly subjects. © 2014 American Society for Bone and Mineral Research
    Preview · Article · Jan 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: Objectives Blood haemoglobin (Hb) declines in elderly men while the adipocyte derived protein adiponectin increases with age. The association between erythropoesis and adiponectin in elderly men is incompletely known. The aim was to determine whether adipokines like adiponectin and leptin are associated with anaemia and Hb in elderly community dwelling men.Design/SettingThe Swedish-Gothenburg MrOS (Osteoporotic Fractures in Men) is a population-based study (n=1010 median age 75.3 years, range 69-81 years).Main Outcome MeasuresWe investigated the associations between adiponectin levels and Hb before and after adjusting for potential confounders (i.e. age, body composition, erythropoietin (EPO), total estradiol, leptin, cystatin C, iron- and B-vitamin status).ResultsIn these older men, age was negatively associated with Hb (r=-0.12, p<0.001) and positively associated adiponectin (r=0.13, p<0.001). In age-adjusted partial correlations, Hb correlated negatively with adiponectin (r=-0.20, p<0.001); this was still significant after multivariable adjustments for age, body composition, EPO, fasting insulin, sex hormones, leptin and ferritin. Anaemic men (66/1005) (Hb <130 g/L) had significantly higher age-adjusted mean adiponectin compared to non-anaemic men (14.0 μg/ml vs. 11.7 μg/ml, p<0.05). In multivariate analysis, adiponectin together with EPO, total estradiol, insulin, albumin, transferrin saturation, HDL-cholesterol, cystatin C, total body fat mass and free T4, but not leptin, explained 35% of the variation in Hb. These results remained after exclusion of men with diabetes.Conclusions Serum adiponectin, but not leptin, correlated negatively and independently with Hb and suggesting a possible role of adiponectin in the age-related Hb decline observed in apparently healthy elderly men.This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Journal of Internal Medicine
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    ABSTRACT: Background 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. Objectives 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. Methods 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. Results 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. Conclusions Low serum levels of DHEA and its sulfate predict an increased risk of CHD, but not CBD, events in elderly men.
    No preview · Article · Oct 2014 · Journal of the American College of Cardiology
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    ABSTRACT: Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.Molecular Psychiatry advance online publication, 7 October 2014; doi:10.1038/mp.2014.107.
    Full-text · Article · Oct 2014 · Molecular Psychiatry
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    ABSTRACT: Objective: The aim of this study was to test whether lower urinary tract symptoms (LUTS) and urinary incontinence are associated with the metabolic syndrome (MetS). The association between LUTS and benign prostatic enlargement (BPE) was also investigated. Material and methods: A cross-sectional, representative risk factor analysis of LUTS, as measured by the International Prostate Symptom Score (IPSS), and urinary incontinence was conducted. Among 950 representative individuals, aged 69-81 years, the association between clinical, anthropometric, endocrine, metabolic and inflammatory factors on the one hand, as both major and minor aspects of MetS, and LUTS and urinary incontinence, on the other hand, was analysed. The prostate gland volume was measured in a subgroup of 155 randomly selected individuals and the association between LUTS and BPE was estimated. Results: No significant association was found between LUTS or urinary incontinence and the major aspects of the MetS. However, in a multivariate analysis, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. Furthermore, in a subgroup of 155 individuals, the prostate gland volume correlated positively with LUTS. Conclusions: The study did not show an association between LUTS or urinary incontinence and the major components of the MetS. However, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. The data confirm the general knowledge that BPE may be one of the causative factors of LUTS.
    No preview · Article · Sep 2014 · Scandinavian Journal of Urology
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    ABSTRACT: Background context: 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. Methods: 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. Results: 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). Conclusions: 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.
    No preview · Article · Sep 2014 · The spine journal: official journal of the North American Spine Society

  • No preview · Article · Sep 2014
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    ABSTRACT: Previous studies have reported an association between exercises during youth and increased areal bone mineral density at old age. The primary aim of this study was to investigate if exercise during growth was independently associated with greater cortical bone size and whole bone strength in weight-bearing bone in old men. The tibia and radius were measured using both peripheral quantitative computed tomography (pQCT)(XCT-2000, Stratec) at the diaphysis and high-resolution pQCT (HR-pQCT)(XtremeCT, Scanco) at the metaphysis to obtain cortical bone geometry and finite element derived bone strength in distal tibia and radius, in 597 men, 79.9 ± 3.4 (mean ± SD) years old. A self-administered questionnaire was used to collect information about previous and current physical activity. In order to determine whether level of exercise during growth and young adulthood or level of current physical activity were independently associated with bone parameters in both tibia and radius, ANCOVA analyses were used. Adjusting for covariates and current physical activity we found that men in the group with the highest level of exercise early in life (regular exercise at competitive level) had higher tibial cortical cross-sectional area (CSA; 6.3%, p < 0.001) and periosteal circumference (PC; 1.6%, p = 0.011) at the diaphysis, and higher estimated bone strength (failure load (7.5%, p < 0.001) and stiffness (7.8%, p < 0.001)) at the metaphysis than men in the subgroup with the lowest level of exercise during growth and young adulthood. Subjects in the group with the highest level of current physical activity had smaller tibial endosteal circumference (EC, 3.6%, p = 0.012) at the diaphysis than subjects with a lower current physical activity, when adjusting for covariates and level of exercise during growth and young adulthood. These findings indicate that exercise during growth can increase the cortical bone size via periosteal expansion while exercise at old age may decrease endosteal bone loss in weight-bearing bone in old men. © 2014 American Society for Bone and Mineral Research.
    No preview · Article · Aug 2014 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research

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7k Citations
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  • 1990-2015
    • Sahlgrenska University Hospital
      • • Department of Cardiology
      • • Department of Geriatrics
      • • Department of Urology
      • • Department of Infectious Diseases
      Goeteborg, Västra Götaland, Sweden
  • 1982-2015
    • University of Gothenburg
      • • Institute of Medicine
      • • Centre for Bone and Arthritis Research (CBAR) (1)
      • • Department of Pathology
      Goeteborg, Västra Götaland, Sweden
  • 2008
    • Uppsala University
      Uppsala, Uppsala, Sweden
    • Uppsala University Hospital
      • Department of Surgical Sciences
      Uppsala, Uppsala, Sweden