| 11. |
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| 12. |
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| 13. |
- Lind, Thomas, et al.
(author)
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Microarray Profiling of Diaphyseal Bone of Rats Suffering from Hypervitaminosis A
- 2012
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In: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 90:3, s. 219-229
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Journal article (peer-reviewed)abstract
- Vitamin A is the only known compound that produces spontaneous fractures in rats. In an effort to resolve the molecular mechanism behind this effect, we fed young male rats high doses of vitamin A and performed microarray analysis of diaphyseal bone with and without marrow after 1 week, i.e., just before the first fractures appeared. Of the differentially expressed genes in cortical bone, including marrow, 98% were upregulated. In contrast, hypervitaminotic cortical bone without marrow showed reduced expression of 37% of differentially expressed genes. Gene ontology (GO) analysis revealed that only samples containing bone marrow were associated with a GO term, which principally represented extracellular matrix. This is consistent with the histological findings of increased endosteal/marrow osteoblast number. Fourteen genes, including Cyp26b1, which is known to be upregulated by vitamin A, were selected and verified by real-time PCR. In addition, immunohistochemical staining of bone sections confirmed that the bone-specific molecule osteoadherin was upregulated. Further analysis of the major gene-expression changes revealed apparent augmented Wnt signaling in the sample containing bone marrow but reduced Wnt signaling in cortical bone. Moreover, induced expression of hypoxia-associated genes was found only in samples containing bone marrow. Together, these results highlight the importance of compartment-specific analysis of bone and corroborate previous observations of compartment-specific effects of vitamin A, with reduced activity in cortical bone but increased activity in the endosteal/marrow compartment. We specifically identify potential key osteoblast-, Wnt signaling-, and hypoxia-associated genes in the processes leading to spontaneous fractures.
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| 14. |
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| 15. |
- Nilsson Sommar, Johan, et al.
(author)
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Hip Fracture Risk and Cadmium in Erythrocytes : A Nested Case-Control Study with Prospectively Collected Samples
- 2014
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In: Calcified Tissue International. - : Springer. - 0171-967X .- 1432-0827. ; 94:2, s. 183-190
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Journal article (peer-reviewed)abstract
- Several studies have investigated the relation between bone mass density and cadmium exposure, but only few studies have been performed on fractures and biomarkers of cadmium. This study analyzed the association between hip fracture risk and cadmium in erythrocytes (Ery-Cd). Prospective samples from the Northern Sweden Health and Disease Study's biobank were used for 109 individuals who later in life had sustained a low-trauma hip fracture, matched with two controls of the same age and gender. The mean concentration of Ery-Cd (±SD) in case samples was 1.3 ± 1.4 versus 0.9 ± 1.0 μg/L in controls. The odds ratio (OR) was 1.63 [95 % confidence interval (CI) 1.10-2.42] for suffering a hip fracture for each microgram per liter increase in Ery-Cd. However, when taking smoking into consideration (never, former, or current), neither Ery-Cd nor smoking showed a statistically significant increase in fracture risk. Using multiple conditional logistic regression with BMI, height, and smoking, the estimated OR for a 1-μg/L increase in Ery-Cd was 1.52 (95 % CI 0.77-2.97). Subgroup analysis showed an increased fracture risk among women (OR = 1.94, 95 % CI 1.18-3.20, for a 1 μg/L increase), which also remained in the multiple analysis (OR = 3.33, 95 % CI 1.29-8.56). This study shows that fracture risk is associated with Ery-Cd. It is, however, not possible to draw firm conclusions on whether cadmium is the causal factor or whether other smoking-related factors cause this association. Subgroup analysis shows that cadmium is a risk factor for hip fracture among women.
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| 16. |
- Nordström, Peter, et al.
(author)
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Do both areal BMD and injurious falls explain the higher incidence of fractures in women than in men?
- 2011
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In: Calcified Tissue International. - : Springer. - 0171-967X .- 1432-0827. ; 89:3, s. 203-210
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Journal article (peer-reviewed)abstract
- The higher incidence of fractures in women than in men is generally attributed to the lower areal bone mineral density (areal BMD, g/cm(2)) of the former. The purpose of the present study was to investigate both areal BMD and injurious falls as risk factors for fractures. In a first cohort, areal BMD was measured in 5,131 men and women (age range 40-95 years). In a second cohort, consisting of 26,565 men and women (age range 40-69 years), a health survey was conducted including questions about lifestyle and medication. Main outcome measures included validated prospective injurious falls and fractures in both cohorts. The higher areal BMD and femoral neck BMD in men compared to women (P < 0.001) were explained by a higher diameter of the femoral neck. Importantly, the diameter of the femoral neck was not associated with fractures in either sex (hazard ratio [HR] 0.94-1.04, P > 0.05 for all), suggesting that a higher areal BMD and lower incidence of osteoporosis in men do not explain their lower incidence of fractures. In contrast, women were more prone to sustain injurious falls than men in both cohorts investigated (HR for women = 1.61 and 1.84, P < 0.001 for both), resulting in a higher incidence of fractures (HR for women = 2.24 and 2.36, P < 0.001 for both). The number of injurious falls and fractures occurring each month during the study period showed a very strong correlation in both women (r = 0.95, P < 0.00001) and men (r = 0.97, P < 0.00001). In summary, low areal BMD, and thus osteoporosis, may not explain the higher fracture incidence in women than in men. Instead, a higher incidence of injurious falls in women was strongly associated with the higher fracture risk.
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| 17. |
- Odén, Anders, 1942, et al.
(author)
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Assessing the impact of osteoporosis on the burden of hip fractures.
- 2013
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In: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 92:1, s. 42-9
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Journal article (peer-reviewed)abstract
- The aim of the study was to determine the number of hip fractures within defined countries for 2010 and the proportion attributable to osteoporosis. The number of incident hip fractures in one year in countries for which data were available was calculated from the population demography in 2010 and the age- and sex-specific risk of hip fracture. The number of hip fractures attributed to osteoporosis was computed as the number of hip fractures that would be saved assuming that no individual could have a femoral neck T-score of less than -2.5 SD (i.e., the lowest attainable T-score was that at the threshold of osteoporosis (=-2.5 SD). The total number of new hip fractures for 58 countries was 2.32 million (741,005 in men and 1,578,809 in women) with a female-to-male ratio of 2.13. Of these 1,159,727 (50 %) would be saved if bone mineral density in individuals with osteoporosis were set at a T-score of -2.5 SD. The majority (83 %) of these "prevented" hip fractures were found in men and women at the age of 70 years or more. The 58 countries assessed accounted for 83.5 % of the world population aged 50 years or more. Extrapolation to the world population using age- and sex-specific rates gave an estimated number of hip fractures of approximately 2.7 million in 2010, of which 1,364,717 were preventable with the avoidance of osteoporosis (264,162 in men and 1,100,555 in women). We conclude that osteoporosis accounts for approximately half of all hip fractures. Strategies to prevent osteoporosis could save up to 50 % of all hip fractures.
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| 18. |
- Olson, Lisa E, et al.
(author)
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The Role of GH/IGF-I-Mediated Mechanisms in Sex Differences in Cortical Bone Size in Mice.
- 2011
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In: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 88:1, s. 1-8
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Journal article (peer-reviewed)abstract
- Cortical bone dimensions are important determinants of bone strength. Gender differences in cortical bone size caused by greater periosteal expansion in males than in females during the pubertal growth spurt are well established both in humans and in experimental animal models. However, the mechanism by which gender influences cortical bone size is still a matter of investigation. The role of androgens and estrogen in pubertal bone growth has been examined in human disorders as well as animal models, such as gonadectomized or sex steroid receptor knockout mice. Based on the findings that growth hormone (GH) and insulin-like growth factor I (IGF-I) are major regulators of postnatal skeletal growth, we and others have predicted that sex hormones interact with the GH/IGF-I axis to regulate cortical bone size. However, studies conflict as to whether estrogen and androgens impact cortical bone size through the canonical pathway, through GH without IGF-I mediation, through IGF-I without GH stimulation, or independent of GH/IGF-I. We review recent data on the impact of sex steroids and components of the GH/IGF axis on sexual dimorphism in bone size. While the GH/IGF-I axis is a major player in regulating peak bone size, the relative contribution of GH/IGF-dependent mechanisms to sex differences in cortical bone size remains to be established.
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