Dan Mellström

Sahlgrenska University Hospital, Goeteborg, Västra Götaland, Sweden

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Publications (245)972.69 Total impact

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    ABSTRACT: 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.
    Scandinavian journal of urology. 09/2014;
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    ABSTRACT: 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.
    The spine journal: official journal of the North American Spine Society 09/2014; · 2.90 Impact Factor
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    ABSTRACT: Aims: Most previous prospective studies suggest that low serum insulin-like growth factor-I (IGF-I) associates with increased risk of cardiovascular disease (CVD) events while other studies suggest that high serum IGF-I associates with increased risk of CVD events. We tested the hypothesis that not only low, but also high, serum IGF-I associate with increased risk of CVD events in elderly men. Methods and Results: Serum IGF-I levels were measured in 2901 elderly men (aged 69 to 81 years) included in the prospective population-based MrOS-Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of follow-up. During follow-up (median 5.1 yrs) 589 of the participants experienced a CVD event. The association between serum IGF-I and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-I levels and CVD events (p<0.01 for nonlinearity). Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio (HR) = 1.25, 95% confidence interval (CI) 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-I associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. Conclusion: Both low and high serum IGF-I levels are risk markers for CVD events in elderly men. The association between high serum IGF-I and CVD events is mainly driven by CHD events.
    The Journal of clinical endocrinology and metabolism. 07/2014;
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    ABSTRACT: Serum adiponectin is a risk factor for fracture. The predictive value attenuates with time in elderly men so that its use for the risk assessment in the long term is questionable. The study underlines the importance of testing the long-term stability of potential risk factors. Introduction High serum adiponectin is associated with an increased risk of fracture in elderly men. The aim of the present study was to determine the impact of adiponectin on the probability of fracture as a function of time. Methods The probability of osteoporotic fracture was computed in 989 elderly men from the MrOS study in Sweden. Baseline data included clinical risk factors for fracture, femoral neck BMD and serum adiponectin. Men were followed for up to 7.4 years with a mean follow up of 5.3 years (range 0.0–7.4 years). Poisson regression was used to model the hazard function for osteoporotic fracture and death to determine the 10 year probability of fracture. Results During follow up, 124 men sustained one or more osteoporotic fracture. There was a significant interaction between adiponectin and time since baseline (p = 0.026) such that the longer time since baseline, the lower the gradient of fracture risk. When using this interaction in the calculation of 10-year probability of fracture, the probabilities of osteoporotic fracture varied little over the range of adiponectin values. Conclusion Serum adiponectin is a risk factor for fracture. Nevertheless, the predictive value attenuates with time so that its use for the risk assessment in the long term is questionable. This study underlines the importance of testing the long-term stability of potential risk factors that might be used in fracture risk assessment.
    Osteoporosis International 07/2014; 25(7). · 4.04 Impact Factor
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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
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 07/2014; · 6.04 Impact Factor
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    ABSTRACT: Background 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. Methods 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 Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97—0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96—0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87—0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
    The Lancet Diabetes and Endocrinology. 06/2014;
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    ABSTRACT: Leukocyte telomere length (LTL) is related to the aging of somatic cells. We hypothesized that LTL is inversely associated with mortality in elderly men. LTL was measured in 2744 elderly men (mean age 75.5, range 69-81 years) included in the prospective population-based MrOS-Sweden study. Mortality data were obtained from national health registers with no loss of follow-up. During the follow-up (mean 6.0years), 556 (20%) of the participants died. Using Cox proportional hazards regression, tertile of LTL did not associate with all-cause mortality [tertile 1 (shortest) or 2 (middle) vs. tertile 3 (longest); hazard ratio (HR)=1.05, 95% confidence interval (CI) 0.85-1.28 and HR=0.97, 95% CI 0.79-1.19, respectively]. Furthermore, LTL did not associate with cancer (197 events) or cardiovascular disease (CVD, 206 events) mortality (tertile 1 vs. tertile 3; HR=0.94, 95% CI 0.67-1.34 and HR=0.94, 95% CI 0.68-1.30, respectively). The lack of association between LTL and mortality remained also after adjustment for multiple covariates. Our results demonstrate that LTL is not associated with all-cause mortality or mortality due to cancer or CVD in elderly men. Further studies are needed to determine whether LTL can predict the risk of mortality in elderly women.
    Experimental gerontology 04/2014; · 3.34 Impact Factor
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    ABSTRACT: Context: Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing testosterone has been regarded as part of normal ageing. However, the association between Hb and serum estradiol is incompletely known. Objective: To determine whether estradiol is associated with anemia/Hb and established determinants of Hb in elderly men without prostate cancer. Design, Setting and Participants: The MrOS (Osteoporotic Fractures in Men) is a population-based study (n=918, median age 75.3 years, range 70-81 years). Main Outcome Measures: We evaluated total estradiol in relation to Hb and adjusted for potential confounders (i.e. age, body mass index (BMI), erythropoietin (EPO), total testosterone, cystatin C, iron- and B-vitamin status). Results: Estradiol correlated negatively with age (r=-0.14, p<0.001). Hb correlated (age adjusted) positively with estradiol (r=0.21, p<0.001) and testosterone (r=0.10, p<0.01). Independent predictors for Hb in multivariate analyses were estradiol, EPO, BMI, transferrin saturation, cystatin C and free T4 but not testosterone. After exclusion of subjects with Hb <130g/L and/or testosterone <8 nmol/L (n=99), the correlation between Hb and testosterone was no longer significant, whereas the associations between Hb and estradiol remained. After adjusting for age, BMI and EPO, men with lower estradiol levels were more likely to have Hb in the lowest quartile of values [OR per SD decrease in estradiol = 1.61 (95% CI 1.34-1.93)]. Anemic subjects (Hb <130 g/L) had lower mean estradiol than non-anemic (67.4 vs 79.4 pmol/L, p<0.001). Conclusions: Estradiol correlated, positively and independently, with Hb. Decreased estradiol might partly explain the age-related Hb decline observed in healthy elderly men.
    The Journal of Clinical Endocrinology and Metabolism 04/2014; · 6.31 Impact Factor
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    ABSTRACT: Context: The key role of serum estradiol (E2) for bone health in men is well established. The effect of serum sex steroids on bone microstructure, measured by high-resolution peripheral quantitative computed tomography (HRpQCT), remains unknown in elderly men. Objective: To examine the associations between serum sex steroids and bone microstructural parameters in older men. Methods: Trabecular and cortical bone microstructure at the tibia was measured by HRpQCT in 440 men (mean 80 years of age) participating in the population-based MrOS Sweden cohort. Serum levels of E2 and testosterone (T) were analyzed with mass spectrometry and free E2 and free T levels were calculated using law-of-mass-action equations. Results: Age-adjusted models demonstrated that E2 and free E2 but not T or free T associated significantly inversely with cortical porosity. The associations between E2 and free E2 and cortical porosity remained significant after further adjustment for height, weight, physical activity, calcium intake and smoking. Models including both serum E2 and T demonstrated that E2 (standardized beta= -0.12, P<0.05) but not T associated independently with cortical porosity. A similar independent association was found for free E2 (standardized beta= -0.12, P<0.05) but not free T. Free E2 associated significantly with trabecular bone volume fraction in age-adjusted models but this association did not remain significant after further adjustment. Conclusions: Serum E2 levels associated inversely with cortical porosity in 80-year-old men. We propose that low serum E2 may reduce cortical bone strength, at least partly by increasing cortical porosity, and, thereby, increase fracture risk in older men.
    The Journal of Clinical Endocrinology and Metabolism 04/2014; · 6.31 Impact Factor
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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.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2014; · 6.04 Impact Factor
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    ABSTRACT: Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged > 55 years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p < 5 × 10− 8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p = 4.6 × 10− 8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p = 0.17), displaying high degree of heterogeneity (I2 = 57%; Qhet p = 0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size > 1.25) may still be consistent with an effect size < 1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.
    Bone 02/2014; 59:20-7. · 4.46 Impact Factor
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    ABSTRACT: Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by x-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA, n=14,260), velocity of sound (VOS, n=15,514) and BMD (n=4,566) in 13 discovery cohorts. Independent replication involved 7 cohorts with GWA data (in silico n=11,452) and new genotyping in 15 cohorts (de novo n=24,902). In combined random effects meta-analysis of the discovery and replication cohorts, 9 SNPs had genome-wide significant (p<5×10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708), and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (p<8.23×10(-14)). In meta-analyses involving 25 cohorts with up to 14,985 fracture cases, six of 10 SNPs associated with heel bone properties at p<5×10(-6) also had the expected direction of association with any fracture (p<0.05), including 3 SNPs with p<0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007), and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
    Human Molecular Genetics 01/2014; · 7.69 Impact Factor
  • Journal of Clinical Densitometry 01/2014; 17(3):400. · 1.71 Impact Factor
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    ABSTRACT: The aim of this study is to evaluate the prevalence and severity of low back pain (LBP) and the influence of sciatica and neurological deficits in old men. Mister osteoporosis Sweden includes 3,014 community-dwelling men aged 69-81 years. At study start 3,009 participants answered questions on LBP, low back pain and sciatica (LBP + SCI) or low back pain and sciatica with associated neurological deficits (LBP + SCI + NEU) during the preceding 12 months. Data are presented as proportions or medians with mid-quartile ranges. Differences between groups were tested by χ(2) test and Kruskall-Wallis test. 24 % had experienced LBP without SCI, 8 % LBP + SCI and 14 % LBP + SCI + NEU. 10 % of the men with LBP, 22 % of those with LBP + SCI, and 36 % of those with LBP + SCI + NEU rated the pain as severe (p < 0.001). 23 % of the men with LBP, 31 % of those with LBP + SCI and 50 % of those with LBP + SCI + NEU reported limitation in activity of daily living (ADL) (p < 0.001). Men with only LBP had to restrict their activities for 7 days (3-14), those with LBP + SCI 6 days (2-14) and those with LBP + SCI + NEU 10 days (3-30) (p < 0.05). The 1-year prevalence of LBP in community living men aged 69-81 years was close to 50 % but for individuals with LBP or LBP + SCI the morbidity was low with more than two-thirds having no limitations in ADL. In men with LBP + SCI + NEU more than one-third rated the pain as severe and close to half had limitations in ADL.
    European Spine Journal 12/2013; · 2.47 Impact Factor
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    ABSTRACT: Ankylosing Spondylitis (AS) is a chronic inflammatory disease with onset in young adults, but little is known about the prevalence in older age groups. Furthermore, there is very limited information of health status of elderly patients with AS. Our objective was to estimate the prevalence of moderate to severe radiographic sacroiliitis in elderly men and its impact on health . A cross-sectional, population-based survey, that included 1005 men aged 69-81 years old, with the primary aim to study risk factors for osteoporosis (MrOS), was used. X-rays of the pelvis and spine were done for the whole population and then examined by two readers. The prevalences of grade 3-4 sacroiliitis, syndesmophytes and spondylophytes were ascertained. Using a self-administered questionnaire, information was obtained on physical activity (PASE), functional status (IADL items), health related quality of life - QoL (SF-12) and back pain (pain question, Quebec Pain Disability Scale items). Fourteen cases with grade 3-4 sacroiliitis were identified, corresponding to a prevalence of 1.4% (95%CI: 0.7-2.4). Eight of the patients with sacroiliitis had both AS-typical and degenerative changes in the spine, 4 had only degenerative changes and 2 had only AS-related changes. There were no statistically significant differences between those with and without radiographic sacroiliitis regarding demographics, anthropometric measures, smoking status or health status, reflected by measures on physical activity, functional status, health related QoL and back pain. The prevalence of moderate to severe radiographic sacroiliitis was estimated to be 1.4% among elderly men in Sweden. Self-reported health was only slightly different in those with sacroiliitis, suggesting that the relative impact of AS is modest in this age group.
    BMC Musculoskeletal Disorders 12/2013; 14(1):352. · 1.88 Impact Factor
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    ABSTRACT: Aims: Fallers and especially recurrent fallers are at high risk for injuries. The aim of this study was to evaluate fall epidemiology in older men with special attention to the influence of age, ethnicity and country of residence. Methods: 10,998 men aged 65 years or above recruited in Hong Kong, the United States (US) and Sweden were evaluated in a cross-sectional retrospective study design. Self-reported falls and fractures for the preceding 12 months were registered through questionnaires. Group comparisons were done by chi-square test or logistic regression. Results: The proportion of fallers among the total population was 16.5% in ages 65-69, 24.8% in ages 80-84 and 43.2% in ages above 90 (P <0.001). The corresponding proportions of recurrent fallers in the same age groups were 6.3%, 10.1% and 18.2%, respectively (P <0.001), and fallers with fractures 1.0%, 2.3% and 9.1%, respectively (P <0.001). The proportion of fallers was highest in the US, intermediate in Sweden and lowest in Hong Kong (in most age groups P <0.05). The proportion of fallers among white men in the US was higher than in white men in Sweden (all comparable age groups P <0.01) but there were no differences in the proportion of fallers in US men with different ethnicity. Conclusions: The proportion of fallers in older men is different in different countries, and data in this study corroborate with the view that society of residence influences fall prevalence more than ethnicity.
    Scandinavian Journal of Public Health 11/2013; · 1.97 Impact Factor
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    ABSTRACT: Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that in healthy controls, to study vBMD in axial compared with peripheral bone, and to explore the relation between vertebral fractures, spinal osteoproliferation, and peripheral bone microarchitecture and density. High-resolution peripheral quantitative computed tomography (HRpQCT) of ultradistal radius and tibia and QCT and dual-energy x-ray absorptiometry (DXA) of lumbar spine were performed in 69 male AS patients (NY criteria). Spinal radiographs were assessed for vertebral fractures and syndesmophyte formation (mSASSS). The HRpQCT measurements were compared with the measurements of healthy controls. The AS patients had lower cortical vBMD in radius (P = 0.004) and lower trabecular vBMD in tibia (P = 0.033), than did the controls. Strong correlations were found between trabecular vBMD in lumbar spine, radius (rS = 0.762; P < 0.001), and tibia (rS = 0.712; P < 0.001).When compared with age-matched AS controls, patients with vertebral fractures had lower lumbar cortical vBMD (-22%; P = 0.019), lower cortical cross-sectional area in radius (-28.3%; P = 0.001) and tibia (-24.0%; P = 0.013), and thinner cortical bone in radius (-28.3%; P = 0.001) and tibia (-26.9%; P = 0.016).mSASSS correlated negatively with trabecular vBMD in lumbar spine (rS = -0.620; P < 0.001), radius (rS = -0.400; p = 0.001) and tibia (rS = -0.475; p < 0.001) and also with trabecular thickness in radius (rS = -0.528; P < 0.001) and tibia (rS = -0.488; P < 0.001).Adjusted for age, syndesmophytes were significantly associated with decreasing trabecular vBMD, but increasing cortical vBMD in lumbar spine, but not with increasing cortical thickness or density in peripheral bone. Estimated lumbar vBMD by DXA correlated with trabecular vBMD measured by QCT (rS = 0.636; P < 0.001). Lumbar osteoporosis, syndesmophytes, and vertebral fractures were associated with both lower vBMD and deteriorated microarchitecture in peripheral bone. The results indicate that trabecular bone loss is general, whereas osteoproliferation is local in AS.
    Arthritis research & therapy 11/2013; 15(6):R179. · 4.27 Impact Factor
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    ABSTRACT: Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2,666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at P<5x10(-8). In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6 x 10(-8). However, the association was not significant across 5,720 cases and 21,791 controls from 14 studies. Fixed-effects meta analyses summary estimate was 1.06 (95% CI: 0.98-1.14; P=0.17), displaying high degree of heterogeneity (I(2)=57%; Qhet p= 0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (P=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size > 1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions are needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.
    Bone 10/2013; · 4.46 Impact Factor
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    ABSTRACT: In a population-based study on cobalamin status and incident fractures in elderly men (n = 790) with an average follow-up of 5.9 years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C. Cobalamin deficiency in elderlies may affect bone metabolism. This study aims to determine whether serum cobalamins or holotranscobalamin (holoTC; the metabolic active cobalamin) predict incident fractures in old men. Men participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) Sweden cohort and without ongoing vitamin B medication were included in the present study (n = 790; age range, 70-81 years). During an average follow-up of 5.9 years, 110 men sustained X-ray-verified fractures including 45 men with clinical vertebral fractures. The risk of fracture (adjusted for age, smoking, BMI, BMD, falls, prevalent fracture, tHcy, cystatin C, 25-OH-vitamin D, intake of calcium, and physical activity (fully adjusted)), increased per each standard deviation decrease in cobalamins (hazard ratio (HR), 1.38; 95 % confidence intervals (CI), 1.11-1.72) and holoTC (HR, 1.26; 95 % CI, 1.03-1.54), respectively. Men in the lowest quartile of cobalamins and holoTC (fully adjusted) had an increased risk of all fracture (cobalamins, HR = 1.67 (95 % CI, 1.06-2.62); holoTC, HR = 1.74 (95 % CI, 1.12-2.69)) compared with quartiles 2-4. No associations between folate or tHcy and incident fractures were seen. We present novel data showing that low levels of holoTC and cobalamins predicting incident fracture in elderly men. This association remained after adjustment for BMI, BMD, tHcy, and cystatin C. However, any causal relationship between low cobalamin status and fractures should be explored in a prospective treatment study.
    Osteoporosis International 10/2013; · 4.04 Impact Factor
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Publication Stats

4k Citations
972.69 Total Impact Points

Institutions

  • 1990–2014
    • Sahlgrenska University Hospital
      • • Department of Urology
      • • Department of Geriatrics
      Goeteborg, Västra Götaland, Sweden
  • 1987–2014
    • University of Gothenburg
      • • Department of Internal Medicine and Clinical Nutrition
      • • Centre for Bone and Arthritis Research (CBAR) (1)
      • • Institute of Medicine
      • • The Wallenberg Laboratory for Cardiovascular and Metabolic Research
      • • Department of Surgery
      • • Department of Pathology
      Goeteborg, Västra Götaland, Sweden
  • 2013
    • University of Bristol
      • School of Social and Community Medicine
      Bristol, England, United Kingdom
  • 2004–2013
    • Alingsås Hospital
      Алингсас, Västra Götaland, Sweden
  • 2012
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
    • McGill University
      • Department of Human Genetics
      Montréal, Quebec, Canada
  • 2009–2012
    • Lund University
      • Department of Clinical Sciences
      Lund, Skåne, Sweden
    • Umeå University
      • Department of Surgical and Perioperative Sciences
      Umeå, Vaesterbotten, Sweden
  • 2010–2011
    • Uppsala University
      • • Department of Surgical Sciences
      • • Department of Medical Sciences
      Uppsala, Uppsala, Sweden
    • Oregon Health and Science University
      • Bone and Mineral Unit
      Portland, OR, United States
  • 2008–2010
    • Uppsala University Hospital
      • Department of Surgical Sciences
      Uppsala, Uppsala, Sweden
    • Laval University
      • Department of Medicine
      Québec, Quebec, Canada
  • 1993
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden