| 123831. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Association between excessive BMI increase during puberty and risk of cardiovascular mortality in adult men: a population-based cohort study.
- 2016
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595. ; 4:12, s. 1017-1024
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Tidskriftsartikel (refereegranskat)abstract
- Being overweight during childhood and adolescence is associated with increased risk of cardiovascular disease in adulthood, but the relative contribution of prepubertal childhood BMI and BMI change during puberty to adult mortality due to cardiovascular disease is unknown. We assessed the contribution of these two distinct developmental BMI parameters for cardiovascular mortality in adult men.As a part of the ongoing population-based BMI Epidemiology Study (BEST) in Gothenburg, Sweden, men born between 1945 and 1961 with information on both their childhood BMI at age 8 years and BMI change during puberty were included in the study and followed up until December, 2013. Participants who died or emigrated before age 20 years were excluded from the analysis. BMI was collected from paediatric growth charts and mandatory military conscription tests. Childhood overweight (BMI of ≥17·9 kg/m(2)) was defined according to the Centers for Disease Control and Prevention's cutoff at 8 years of age, and BMI change during puberty was defined as the difference between young adult BMI and childhood BMI (BMI at age 20 years minus BMI at age 8 years). Information on mortality was retrieved from high quality national registers with the participants' ten-digit personal identity number. We used Cox proportional hazard regression to analyse the association between exposures and mortality. The ethics committee of the University of Gothenburg, Sweden, approved the study and waived the requirement for written informed consent.We followed 37672 Swedish men from age 20 years for a mean of 37·8 years (1422185 person-years follow-up). 3188 all-cause deaths and 710 cardiovascular deaths occurred during follow-up. The correlation between childhood BMI and BMI change during puberty was marginal (r=0·06). BMI change during puberty, but not childhood BMI, was independently associated with adult all-cause and cardiovascular mortality in men. Boys that became overweight during puberty (HR 2·39; 95% CI 1·86-3·09) and boys who were overweight consistently throughout childhood and puberty (1·85; 1·28-2·67), but not boys overweight in childhood that normalised during puberty (0·99, 0·65-1·50), had increased risk of cardiovascular mortality compared with participants who were not overweight in childhood or as young adults. The association between BMI change during puberty and cardiovascular mortality was non-linear with a substantial association above a threshold of 6·7 units increase in BMI.Excessive BMI increase during puberty is a risk marker of adult cardiovascular mortality. These results indicate that BMI should be monitored during puberty to identify boys with increased risk of adult cardiovascular mortality.Swedish Research Council, the Swedish Government (under the Avtal om Läkarutbildning och Medicinsk Forskning [Agreement for Medical Education and Research]), the Lundberg Foundation, the Torsten Söderberg Foundation, the Novo Nordisk Foundation, the Knut and Alice Wallenberg Foundation, and the Anna Ahrenberg Foundation.
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| 123832. |
- Ohlsson, Claes, 1965
(författare)
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Bone metabolism in 2012: Novel osteoporosis targets.
- 2013
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Ingår i: Nature reviews. Endocrinology. - : Springer Science and Business Media LLC. - 1759-5037 .- 1759-5029. ; 9:2, s. 72-4
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Tidskriftsartikel (refereegranskat)abstract
- Researchers are trying to develop more efficient and safer antifracture treatments. Besides the ongoing promising clinical trials involving antibodies to the Wnt antagonist sclerostin or inhibition of the osteoclast enzyme cathepsin K, the year 2012 has seen several novel osteoporosis targets identified by using different methodological approaches.
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| 123833. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Cortical consolidation due to increased mineralization and endosteal contraction in young adult men: a five-year longitudinal study.
- 2011
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96:7, s. 2262-9
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Tidskriftsartikel (refereegranskat)abstract
- Peak bone mass is an important factor in the lifetime risk of developing osteoporosis. Large, longitudinal studies investigating the age of attainment of site-specific peak bone mass are lacking. OBJECTIVE AND MAIN OUTCOME MEASURES: The main outcome measures were to determine the site-specific development of peak bone mass in appendicular and axial skeletal sites and in the trabecular and cortical bone compartments, using both dual x-ray absorptiometry and peripheral computed tomography.In total, 833 men [aged 24.1 ± 0.6 yr (mean ± sd)] from the original population-based Gothenburg Osteoporosis and Obesity Determinants Study (n = 1068) were included in this follow-up examination at 61.2 ± 2.3 months. Areal bone mineral density (aBMD) was measured with dual x-ray absorptiometry, whereas cortical and trabecular volumetric bone mineral density and bone size were measured by peripheral computed tomography at baseline and at the 5-yr follow-up.During the 5-yr study period, aBMD of the total body, lumbar spine, and radius increased by 3.4, 4.2, and 7.8%, respectively, whereas a decrease in aBMD of the total hip of 1.9% was observed (P < 0.0001). Increments of 2.1 and 0.7% were seen for cortical volumetric bone mineral density of the radius and tibia, respectively (P < 0.0001), whereas cortical thickness increased by 3.8% at the radius and 6.5% at the tibia due to diminished endosteal circumference (radius 2.3% and tibia 4.6%, P < 0.0001).aBMD decreased at the hip but increased at the spine and radius, in which the increment was explained by continued mineralization and augmented cortical thickness due to endosteal contraction in men between ages 19 and 24 yr.
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| 123834. |
- Ohlsson, Claes, 1965, et al.
(författare)
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DHEA and mortality: What is the nature of the association?
- 2015
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Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 145C, s. 248-253
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Tidskriftsartikel (refereegranskat)abstract
- Although very little is known about the importance of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) in human physiology and pathophysiology, emerging observations imply pivotal roles of DHEA/-S. One such observation is the association between serum DHEA/-S levels and mortality risk. In this review, we focus on the literature addressing DHEA/-S and mortality with the aim to describe and discuss patterns and potential underlying mechanisms. Although the literature reports somewhat inconsistent results, we conclude that several larger population-based studies support an association between low DHEA/-S and risk of death, at least in elderly men. In women, the association may not be present; alternatively, there may be a U-shaped association. In men, most available evidence suggests an association with cardiovascular (CV) mortality rather than cancer mortality. Further, there are biologically plausible mechanisms for an effect of DHEA/-S on the development of CV disease. On the other hand, there is also strong evidence supporting that any disease may lower DHEA/-S. Thus, the cause-effect relation of this association is less clear. Future studies may employ a mendelian randomization approach using genetic determinants of DHEA-S levels as predictors of clinical outcomes, to delineate the true nature of the association between DHEA/-S and mortality.
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| 123835. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Early puberty and risk for type 2 diabetes in men
- 2020
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63, s. 1141-1150
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The association between pubertal timing and type 2 diabetes, independent of prepubertal BMI, is not fully understood. The aim of the present study was to evaluate the association between pubertal timing and risk of adult type 2 diabetes, independent of prepubertal BMI, in Swedish men. Methods We included 30,697 men who had data for BMI at age 8 and 20 years and age at Peak Height Velocity (PHV), an objective assessment of pubertal timing, available from the BMI Epidemiology Study Gothenburg (BEST Gothenburg), Sweden. Information on type 2 diabetes (n = 1851) was retrieved from the Swedish National Patient Register. HRs and 95% CIs were estimated by Cox regression analysis. We observed violations of the assumption of proportional hazards for the association between age at PHV and the risk of type 2 diabetes and therefore split the follow-up period at the median age of type 2 diabetes diagnosis (57.2 years of age) to define early (<= 57.2 years) and late (>57.2 years) type 2 diabetes diagnosis. Results Age at PHV was inversely associated with both early (HR 1.28 per year decrease in age at PHV, 95% CI 1.21, 1.36) and late (HR 1.13, 95% CI 1.06, 1.19) type 2 diabetes. After adjustment for childhood BMI, the associations between age at PHV and both early (HR 1.24, 95% CI 1.17, 1.31) and late (HR 1.11, 95% CI 1.05, 1.17) type 2 diabetes were similar. Moreover, early age at PHV predicted insulin treatment of type 2 diabetes (OR 1.25 per year decrease in age at PHV, 95% CI 1.17, 1.33). Assuming a higher risk among those with an age at PHV below the median, the population attributable factor indicates that 15% fewer of the diagnosed individuals would have developed type 2 diabetes had they not reached puberty early. Conclusions/interpretation These findings indicate that early puberty may be a novel independent risk factor for type 2 diabetes.
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| 123836. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Effects of the gut microbiota on bone mass.
- 2015
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Ingår i: Trends in endocrinology and metabolism: TEM. - : Elsevier BV. - 1879-3061 .- 1043-2760. ; 26:2, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota (GM), the commensal bacteria living in our intestine, performs numerous useful functions, including modulating host metabolism and immune status. Recent studies demonstrate that the GM is also a regulator of bone mass and it is proposed that the effect of the GM on bone mass is mediated via effects on the immune system, which in turn regulates osteoclastogenesis. Under normal conditions, the skeleton is constantly remodeled by bone-forming osteoblasts (OBs) and bone-resorbing osteoclasts (OCLs), and imbalances in this process may lead to osteoporosis. Here we review current knowledge on the possible role for the GM in the regulation of bone metabolism and propose that the GM might be a novel therapeutic target for osteoporosis and fracture prevention.
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| 123837. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Estrogen receptor-α expression in neuronal cells affects bone mass.
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:3, s. 983-988
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Tidskriftsartikel (refereegranskat)abstract
- It has generally been assumed that bone mass is controlled by endocrine mechanisms and the local bone environment. Recent findings demonstrate that central pathways are involved in the regulation of bone mass. Estrogen is involved in the regulation of bone homeostasis and the CNS is also a target for estrogen actions. The aim of this study was to investigate in vivo the role of central estrogen receptor-α (ERα) expression for bone mass. Nestin-Cre mice were crossed with ERα(flox) mice to generate mice lacking ERα expression specifically in nervous tissue (nestin-ERα(-/-)). Bone mineral density was increased in both the trabecular and cortical bone compartments in nestin-ERα(-/-) mice compared with controls. Femoral bone strength was increased in nestin-ERα(-/-) mice, as demonstrated by increased stiffness and maximal load of failure. The high bone mass phenotype in nestin-ERα(-/-) mice was mainly caused by increased bone formation. Serum leptin levels were elevated as a result of increased leptin expression in white adipose tissue (WAT) and slightly increased amount of WAT in nestin-ERα(-/-) mice. Leptin receptor mRNA levels were reduced in the hypothalamus but not in bone. In conclusion, inactivation of central ERα signaling results in increased bone mass, demonstrating that the balance between peripheral stimulatory and central inhibitory ERα actions is important for the regulation of bone mass. We propose that the increased bone mass in nestin-ERα(-/-) mice is mediated via decreased central leptin sensitivity and thereby increased secretion of leptin from WAT, which, in turn, results in increased peripheral leptin-induced bone formation.
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| 123838. |
- Ohlsson, Claes, 1965, et al.
(författare)
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High Serum Testosterone is Associated with Reduced Risk of Cardiovascular Events in Elderly Men
- 2011
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 58:16, s. 1674-1681
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We tested the hypothesis that serum total testosterone and sex hormone-binding globulin (SHBG) levels predict cardiovascular (CV) events in community-dwelling elderly men. Background Low serum testosterone is associated with increased adiposity, an adverse metabolic risk profile, and atherosclerosis. However, few prospective studies have demonstrated a protective link between endogenous testosterone and CV events. Polymorphisms in the SHBG gene are associated with risk of type 2 diabetes, but few studies have addressed SHBG as a predictor of CV events. Methods We used gas chromatography/mass spectrometry to analyze baseline levels of testosterone in the prospective population-based MrOS (Osteoporotic Fractures in Men) Sweden study (2,416 men, age 69 to 81 years). SHBG was measured by immunoradiometric assay. CV clinical outcomes were obtained from central Swedish registers. Results During a median 5-year follow-up, 485 CV events occurred. Both total testosterone and SHBG levels were inversely associated with the risk of CV events (trend over quartiles: p = 0.009 and p = 0.012, respectively). Men in the highest quartile of testosterone (>= 550 ng/dl) had a lower risk of CV events compared with men in the 3 lower quartiles (hazard ratio: 0.70, 95% confidence interval: 0.56 to 0.88). This association remained after adjustment for traditional CV risk factors and was not materially changed in analyses excluding men with known CV disease at baseline (hazard ratio: 0.71, 95% confidence interval: 0.53 to 0.95). In models that included both testosterone and SHBG, testosterone but not SHBG predicted CV risk. Conclusions High serum testosterone predicted a reduced 5-year risk of CV events in elderly men. (J Am Coll Cardiol 2011;58:1674-81) (C) 2011 by the American College of Cardiology Foundation
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| 123839. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Inducible Wnt16 inactivation: WNT16 regulates cortical bone thickness in adult mice.
- 2018
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Ingår i: The Journal of endocrinology. - 1479-6805. ; 237:2, s. 113-122
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Tidskriftsartikel (refereegranskat)abstract
- Substantial progress has been made in the therapeutic reduction of vertebral fracture risk in patients with osteoporosis, but non-vertebral fracture risk has been improved only marginally. Human genetic studies demonstrate that the WNT16 locus is a major determinant of cortical bone thickness and non-vertebral fracture risk and mouse models with life-long Wnt16 inactivation revealed that WNT16 is a key regulator of cortical thickness. These studies, however, could not exclude that the effect of Wnt16 inactivation on cortical thickness might be caused by early developmental and/or growth effects. To determine the effect of WNT16 specifically on adult cortical bone homeostasis, Wnt16 was conditionally ablated in young adult and old mice through tamoxifen-inducible Cre-mediated recombination using CAG-Cre-ER; Wnt16flox/flox (Cre-Wnt16flox/flox) mice. First, 10-week-old Cre-Wnt16flox/flox and Wnt16flox/flox littermate control mice were treated with tamoxifen. Four weeks later, Wnt16 mRNA levels in cortical bone were reduced and cortical thickness in femur was decreased in Cre-Wnt16flox/flox mice compared to Wnt16flox/flox mice. Then, inactivation of Wnt16 in 47-week-old mice (evaluated four weeks later) resulted in a reduction of Wnt16 mRNA levels, cortical thickness and cortical bone strength with no effect on trabecular bone volume fraction. Mechanistic studies demonstrated that the reduced cortical bone thickness was caused by a combination of increased bone resorption and reduced periosteal bone formation. In conclusion, WNT16 is a crucial regulator of cortical bone thickness in young adult and old mice. We propose that new treatment strategies targeting the adult regulation of WNT16 might be useful to reduce fracture risk at cortical bone sites.
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| 123840. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Low Serum Levels of Dehydroepiandrosterone Sulfate Predict All-Cause and Cardiovascular Mortality in Elderly Swedish Men
- 2010
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:9, s. 4406-4414
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Tidskriftsartikel (refereegranskat)abstract
- Context: The age-related decline in dehydroepiandrosterone (DHEA) levels is thought to be of importance for general and vascular aging. However, data on the association between DHEA and mortality are conflicting. Objectives: We tested the hypothesis that low serum DHEA and DHEA sulfate (DHEA-S) levels predict all-cause and cardiovascular disease (CVD) death in elderly men. Design, Setting, and Participants: We used gas/liquid chromatography-mass spectrometry to analyze baseline levels of DHEA and DHEA-S in the prospective population-based MrOS Sweden study (2644 men, aged 69-81 yr). Mortality data were obtained from central registers and analyzed using Cox proportional hazards regressions. Main Outcome Measures: All-cause and CVD mortality by serum DHEA(-S) levels. Results: During a mean 4.5-yr follow-up, 328 deaths occurred. Low levels of DHEA-S (quartile 1 vs. quartiles 2-4), predicted death from all causes [hazard ratio (HR) 1.54,95% confidence interval (CI) 1.21-1.96; adjusted for traditional cardiovascular risk factors], from CVD (n = 123 deaths; HR 1.61, 95% CI 1.10-2.37) and ischemic heart disease (n = 73; HR 1.67, 95% CI 1.02-2.74) but not cancer. Analyses with DHEA gave similar results. The association between low DHEA-S and CVD death remained after adjustment for C-reactive protein and circulating estradiol and testosterone levels. When stratified by the median age of 75.4 yr, the mortality prediction by low DHEA-S was more pronounced among younger (age adjusted HR for CVD death 2.64, 95% CI 1.37-5.09) than older men (HR 1.30, 95% CI 0.83-2.04). Conclusions: Low serum levels of DHEA(-S) predict death from all causes, CVD, and ischemic heart disease in older men.
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