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- Johansson, Sara, et al.
(författare)
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Subclinical hypervitaminosis A causes fragile bones in rats
- 2002
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Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 31:6, s. 685-689
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Tidskriftsartikel (refereegranskat)abstract
- Excessive intake of vitamin A has been associated with an increased risk of hip fracture in humans. This finding has raised the question of whether long-term intake of relatively moderate doses ("subclinical" hypervitaminosis A) contributes to fracture risk. Although it has been known for more than half a century that toxic doses of vitamin A lead to spontaneous fractures in rats, the lowest intake that induces adverse effects is not known, and the result of exposure to excessive doses that do not cause general toxicity has been rarely investigated. In this study, mature female rats were fed a standard diet with 12 IU vitamin A/g pellet (control, C), or standard diet supplemented with either 120 IU ("10 x C") or 600 IU ("50 x C") vitamin A/g pellet for 12 weeks. Fifteen animals were included in each group. The supplemented diets correspond to a vitamin A intake of approximately 1800 IU/day and 9000 IU/day, respectively. The latter dose is about one third of that previously reported to cause skeletal lesions. At the end of the study, serum retinyl esters were elevated 4- (p < 0.01) and 20-fold (p < 0.001) and the total amount of liver retinoid had increased 3- (p < 0.001) and 7-fold (p < 0.001) in the 10 x C and 50 x C group, respectively. The animals showed no clinical signs of general toxicity, and there were no significant bone changes in the 10 x C group. However, in the 50 x C group, a characteristic thinning of the cortex (cortical area -6.5% [p < 0.001]) and reduction of the diameter of the long bones were evident (bone cross-sectional area -7.2% [p < 0.01] at the midshaft and -11.0% [p < 0.01] at the metaphysis), as measured by peripheral quantitative computed tomography. In agreement with these data and a decreased polar strength strain index (-14.0%, p < 0.01), the three-point bending breaking force of the femur was reduced by 10.3% (p < 0.01) in the 50 x C group. These data indicate that the negative skeletal effects appear at a subchronic vitamin A intake of somewhere between 10 and 50 times the standard diet. This level is considerably lower than previously reported. Our results suggest that long-term ingestion of modest excesses of vitamin A may contribute to fracture risk.
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| 2. |
- Lind, Monica, et al.
(författare)
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Torsional testing and peripheral quantitative computed tomography in rat humerus
- 2001
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 29:3, s. 265-270
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral quantitative computed tomography (pQCT) is a noninvasive method mainly used to evaluate the densitometric and geometric properties of bone. In the present study, we evaluate the different variables provided by pQCT examination and their ability to predict the mechanical strength properties of the rat humerus. Humeri from 68 female rats were utilized. These humeri represented bone with a wide range of mechanical and densitometric properties as well as geometric dimensions. Various characteristics, such as volumetric cortical density, total mineral content, cortical thickness, total cross-sectional area, cortical area, and polar strength strain index (SSI), were measured by pQCT. The reproducibility of these measurements was good, with a coefficient of variation (CV) ranging from 0.8% to 4.9%. Bone composition (e.g., ash weight, water content, and inorganic content) and bone dimensions (e.g., length, waist, and volume) were also determined. The mechanical properties (maximum torque, torsion at failure, and stiffness) were measured by torsional testing. Stepwise multiple linear regression was performed to identify the best explanatory variables for each mechanical parameter. Total cross-sectional area and polar SSI were equally well correlated to stiffness (r = 0.57, p < 0.001), whereas ash weight was superior to the pQCT variables to explain maximum torque (r = 0.42, p < 0.001). No other independent pQCT variable entered the two models in the stepwise regression analysis. It was found to be feasible to measure properties of the rat humerus with pQCT. Cross-sectional area and the polar SSI were shown to be the best explanatory variables for stiffness, whereas ash weight was the best predictor for maximum torque.
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| 3. |
- Michaëlsson, Karl, 1959-, et al.
(författare)
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Dietary calcium and vitamin D intake in relation to osteoporotic fracture risk
- 2003
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Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 32:6, s. 694-703
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Tidskriftsartikel (refereegranskat)abstract
- The etiologic role of dietary calcium and vitamin D intake in primary prevention of osteoporotic fractures is uncertain, despite considerable research efforts. With the aim to examine these associations with an improved precision, we used data from a large population-based prospective cohort study in central Sweden. We estimated nutrient intake from a self-administered food-frequency questionnaire filled in by 60,689 women, aged 40-74 years at baseline during 1987-1990. During follow-up, we observed 3986 women with a fracture at any site and 1535 with a hip fracture. Rate ratio of fractures (RR) and 95% CI were estimated using Cox proportional hazards models. We found no dose-response association between dietary calcium intake and fracture risk. The age-adjusted RR of hip fracture was 1.01 (95% CI 0.96-1.06) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 (95% CI 0.96-1.03). Furthermore, women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes: RR 1.07 (95% CI 0.92-1.24) and RR 1.00 (95% CI 0.79-1.27), respectively. Vitamin D intake was not associated with fracture risk. Furthermore, women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures (95% CI 0.88-1.17). Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women.
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| 4. |
- Michaëlsson, Karl, 1959-, et al.
(författare)
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Use of low potency estrogens does not reduce the risk of hip fracture
- 2002
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Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 30:4, s. 613-618
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Tidskriftsartikel (refereegranskat)abstract
- High endogenous sexual hormone levels and use of medium potency estrogens are associated with a reduced risk of hip fracture in postmenopausal women. However, it is not clear if low potency estrogens confer the same benefits as the more widely used forms of menopausal hormone replacement. We examined the association between postmenopausal use of low potency estrogens, mainly estriol, and hip fracture risk in a population-based, case-control study. Using data from mailed questionnaires and telephone interviews, we analyzed the association between low potency estrogen use and hip fracture risk among 1327 cases, 50-81 years of age, and 3262 randomly selected age-matched controls. Ever use of low potency estrogens was reported by 19% of the cases and 23% of controls. Compared to with never users of any hormone replacement therapy, ever users of low potency estrogens had a multivariate odds ratio (OR) for hip fracture of 0.96 (95% confidence interval [CI] 0.67-1.39). Current use was also not associated with a reduction in risk: OR 0.94 (95% CI 0.58-1.53), and longer duration of use was also not associated with a risk reduction. Even current use of the highest dose of oral estriol (2 mg/day) conferred no risk reduction (OR 1.01, 95% CI 0.61-1.67) compared with never use of hormone replacement therapy. After exclusion of ever users of medium potency estrogens from the analyses, we found a risk reduction of fracture among current vaginal low potency estrogen users (multivariate OR 0.67, 95% CI 0.49-0.92). In contrast to medium potency estrogens, low potency estrogens did not confer a substantial overall reduction in hip fracture risk.
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| 7. |
- Bergström, I., et al.
(författare)
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Prednisolone treatment reduces the osteogenic effects of loading in mice
- 2018
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 112, s. 10-18
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoid treatment, a major cause of drug-induced osteoporosis and fractures, is widely used to treat inflammatory conditions and diseases. By contrast, mechanical loading increases bone mass and decreases fracture risk. With these relationships in mind, we investigated whether mechanical loading interacts with GC treatment in bone. Three-month-old female C57BL/6 mice were treated with high-dose prednisolone (15 mg/60 day pellets/mouse) or vehicle for two weeks. During the treatment, right tibiae were subjected to short periods of cyclic compressive loading three times weekly, while left tibiae were used as physiologically loaded controls. The bones were analyzed using peripheral quantitative computed tomography, histomorphometry, real-time PCR, three-point bending and Fourier transform infrared micro-spectroscopy. Loading alone increased trabecular volumetric bone mineral density (vBMD), cortical thickness, cortical area, osteoblast-associated gene expression, osteocyte- and osteoclast number, and bone strength. Prednisolone alone decreased cortical area and thickness and osteoblast-associated gene expression. Importantly, prednisolone treatment decreased the load-induced increase in trabecular vBMD by 57% (p < 0.001) and expression of osteoblast-associated genes, while completely abolishing the load-induced increase in cortical area, cortical thickness, number of osteocytes and osteoclasts, and bone strength. When combined, loading and prednisolone decreased the collagen content. In conclusion, high-dose prednisolone treatment strongly inhibits the loading-induced increase in trabecular BMD, and abolishes the loading-induced increase in cortical bone mass. This phenomenon could be due to prednisolone inhibition of osteoblast differentiation and function.
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