| 1. |
- Almehed, Katarina, 1966, et al.
(författare)
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Prevalence and risk factors of vertebral compression fractures in female SLE patients.
- 2010
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Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: INTRODUCTION: Our objective was to determine the frequency of and factors associated with prevalent vertebral compression fractures in female SLE patients attending rheumatologists in Western Sweden. METHODS: In this cross sectional study 150 women were included. They were examined with x-ray of thoracic and lumbar spine (Th4-L4). A reduction of at least 20% of any vertebral height, assessed by Genant's semiquantitative method, was defined as a fracture. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA). RESULTS: Median patient age was 47 years (20-82) and disease duration 11 years (1-41). Only 6 (4%) women had a history of clinical compressions whereas 43 (29%) had at least one radiological fracture each. The patients with at least one fracture at any site were characterized by higher age (p<0.001), being postmenopausal (p<0.01), higher Systemic Lupus International Collaborative Clinics Damage Index (p<0.05), lower BMD total hip and femoral neck (p<0.05), more peripheral fractures (p< 0.01), medication with bisphosphonates (p<0.05) and calcium and vitamin D3 (p<0.05). There were no significant differences regarding current or cumulative glucocorticosteroid dose between the groups. In logistic regression analyses high age remained as risk factor of at least one vertebral fracture at any site whereas low BMD in total hip was associated with vertebral fracture in lumbar spine. CONCLUSION: Radiological compression fractures are common but seldom diagnosed in SLE patients. High age and low BMD in total hip, but not in spine, was associated with vertebral fractures.
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| 2. |
- Andersson, Niklas, 1970, et al.
(författare)
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A variant near the interleukin-6 gene is associated with fat mass in Caucasian men
- 2010
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 34:6, s. 1011-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.
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| 3. |
- Börjesson, Anna E, et al.
(författare)
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The role of estrogen receptor-alpha in growth plate cartilage for longitudinal bone growth.
- 2010
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Ingår i: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:12, s. 2414-24
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens enhance skeletal growth during early sexual maturation while high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the GH/IGF-I axis. To determine the role of ERalpha in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERalpha. Although mice with total ERalpha inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-I axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERalpha inactivation. High dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERalpha(-/-) mice. Adult cartilage-specific ERalpha(-/-) mice continued to grow after four months of age while growth was limited in control mice, resulting in increased femur length in one-year-old cartilage-specific ERalpha(-/-) mice compared with control mice. We conclude that during early sexual maturation ERalpha in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice. (c) 2010 American Society for Bone and Mineral Research.
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| 4. |
- Darelid, Anna, et al.
(författare)
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Trabecular Volumetric Bone Mineral Density is Associated With Previous Fracture During Childhood and Adolescence in Males - The GOOD Study.
- 2010
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Ingår i: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:3, s. 537-44
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Areal bone mineral density (aBMD) measured with dual X-ray absorptiometry (DXA) has been associated with fracture risk in children and adolescents, but it remains unclear whether this association is due to volumetric BMD (vBMD) of the cortical and/or trabecular bone compartments or the bone size. The aim of this study was to determine whether vBMD or bone size was associated with x-ray verified fractures in men during growth. In total, 1068 men (age 18.9+/-0.6 yrs), were included in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) study. Areal BMD was measured by DXA, while cortical and trabecular vBMD and bone size were measured by peripheral quantitative computerized tomography (pQCT). X-ray records were searched for fractures. Self reported fractures in 77 men could not be confirmed in these records. These men were excluded, resulting in 991 included men, of which 304 men had an x-ray verified fracture and 687 were non-fracture subjects. Growth charts were used to establish the age of peak height velocity (PHV, n=600). Men with prevalent fractures had lower aBMD (lumbar spine 2.3%, p=0.005; total femur 2.6%, p=0.004, radius 2.1%, p<0.001) at all measured sites than men without fracture. Using pQCT measurements, we found that men with a prevalent fracture had markedly lower trabecular vBMD (radius: 6.6 %, p=7.5x10(-8); tibia: 4.5 %, p=1.7x10(-7)) as well as slightly lower cortical vBMD (radius: 0.4 %, p=0.0012; tibia: 0.3 %, p=0.015), but not reduced cortical cross sectional area, than men without fracture. Every SD decrease in trabecular vBMD of the radius and tibia was associated with 1.46 (radius CI 1.26-1.69 (95% CI); tibia CI 1.26-1.68) times increased fracture prevalence. The peak fracture incidence coincided with the timing of PHV (+/-1 year). In conclusion, trabecular vBMD, but not aBMD, was independently associated with prevalent x-ray verified fractures in young men. Further studies are needed to determine if assessment of trabecular vBMD could enhance prediction of fractures during growth in males.
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| 5. |
- Engdahl, Cecilia, 1983, et al.
(författare)
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Amelioration of collagen-induced arthritis and immune-associated bone loss through signaling via estrogen receptor alpha, and not estrogen receptor beta or G protein-coupled receptor 30.
- 2010
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Ingår i: Arthritis and rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 62:2, s. 524-33
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The effects of estrogen may be exerted via the nuclear estrogen receptors (ERs) ERalpha or ERbeta or via the recently proposed transmembrane estrogen receptor G protein-coupled receptor 30 (GPR-30). The purpose of this study was to elucidate the ER specificity for the ameliorating effects of estrogen on arthritis and bone loss in a model of postmenopausal rheumatoid arthritis (RA). METHODS: Female DBA/1 mice underwent ovariectomy or sham operation, and type II collagen-induced arthritis was induced. Mice were treated subcutaneously 5 days/week with the specific agonists propylpyrazoletriol (PPT; for ERalpha), diarylpropionitrile (DPN; for ERbeta), G1 (for GPR-30), or with a physiologic dose of estradiol. Clinical arthritis scores were determined continuously. At termination of the study, bone mineral density (BMD) was analyzed, paws were collected for histologic assessment, serum was analyzed for cytokines and markers of bone and cartilage turnover, and bone marrow was subjected to fluorescence-activated cell sorting. RESULTS: Treatment with PPT as well as estradiol dramatically decreased the frequency and severity of arthritis. Furthermore, estradiol and PPT treatment resulted in preservation of bone and cartilage, as demonstrated by increased BMD and decreased serum levels of bone resorption markers and cartilage degradation markers, whereas no effect was seen after DPN or G1 treatment. CONCLUSION: In a well-established model of postmenopausal RA, ERalpha, but not ERbeta or GPR-30 signaling, was shown to ameliorate the disease and the associated development of osteoporosis. Since long-term treatment with estrogen has been associated with significant side effects, increased knowledge about the mechanisms behind the beneficial effects of estrogen is useful in the search for novel treatments of postmenopausal RA.
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| 6. |
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| 7. |
- Fagman, Johan Bourghardt, 1980, et al.
(författare)
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Androgen receptor-dependent and independent atheroprotection by testosterone in male mice.
- 2010
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 151:11, s. 5428-37
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Tidskriftsartikel (refereegranskat)abstract
- The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P < 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P < 0.001) and ARKO mice (by 24%, P < 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P < 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P < 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.
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| 8. |
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| 9. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 10. |
- Hulthén, Lena, 1947, et al.
(författare)
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Salt intake in young Swedish men.
- 2010
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Ingår i: Public health nutrition. - 1475-2727. ; 13:5, s. 601-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To measure dietary salt intake in a Swedish population. DESIGN: A cross-sectional study with measured 24 h urinary excretion of Na and K. Completeness of urine collection was assessed using p-aminobenzoic acid. The subjects were interviewed on their habitual food intake. SETTING: Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: Eighty-six young men (age 18-20 years), randomly selected from the population of Gothenburg. Seven men were excluded due to incomplete urine collection. RESULTS: The mean excretion of Na and K over 24 h was 198 and 84 mmol, respectively (corresponding to 11.5 g NaCl and 3.3 g K). The mean 24 h excretion in the highest quartile of Na excretion was 297 mmol Na and 105 mmol K, and in the lowest quartile, 100 mmol Na and 68 mmol K. The mean Na:K ratio was 2.3, and respectively 3.2 and 1.8 in the highest and lowest Na excretion quartiles. Calculated energy intake did not differ between the highest and lowest quartiles of Na excretion, but body weight, BMI and the intake of certain foods known to be Na-rich did. CONCLUSIONS: Salt intake in young men was alarming high and even subjects in the lowest quartile of Na excretion did not meet present recommendations to limit salt intake to 5-6 g/d. At this point we can only speculate what the consequences of the high salt intake may be for CVD and stroke later in life. Regulation of the salt content in processed and fast food and in snacks is advocated, to curtail the salt burden on society imposed by the food industry.
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