| 1. |
- 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. |
- Kanis, J.A., et al.
(författare)
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Prediction of fracture from low bone mineral density measurements overestimates risk
- 2000
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Ingår i: Bone (New York, N.Y.). - : Elsevier Inc. - 1873-2763 .- 8756-3282. ; 26:4, s. 387-391
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Tidskriftsartikel (refereegranskat)abstract
- There is a well-established relationship between bone mineral density (BMD) and fracture risk. Estimates of the relative risk of fracture from BMD have been derived mainly from short-term studies in which the correlation between BMD at assessment and BMD in later life ranged from 0.8 to 0.9. Because individuals lose bone mineral at different rates throughout later life, the long-term predictive value of low BMD is likely to decrease progressively with time. This article examines and formalizes the relationship between current BMD, correlation coefficients, and long-term risk. The loss of predictive value has important implications for early assessment and supports the view that measurements should be optimally targeted at the time interventions are contemplated and, when necessary, repeated in later life.
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| 3. |
- Kanis, J.A, et al.
(författare)
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Risk of hip fracture according to the World Health Organization criteria for osteopenia and osteoporosis
- 2000
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Ingår i: Bone. - : Elsevier Inc. - 1873-2763 .- 8756-3282. ; 27:5, s. 585-590
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Tidskriftsartikel (refereegranskat)abstract
- The risk of hip fracture is commonly expressed as a relative risk. The aim of this study was to examine the utility of relative risks of hip fracture in men and women using World Health Organization (WHO) diagnostic criteria for low bone mass and osteoporosis. Reference data for bone mineral density (BMD) at the femoral neck, from the third National Health and Nutrition Examination Survey (NHANES III), were applied to the population of Sweden. Relative risks (RRs) were calculated from the known relationship between BMD at the femoral neck and hip fracture risk. The apparent prevalence of low bone mass and osteoporosis depended on the segment of the young population chosen for reference ranges. Using a reference derived from women aged 20–29 years, the prevalence of osteoporosis was 21.2% in women between the ages of 50 and 84 years and 6.3% in men. The RRs associated with osteoporosis depended markedly on the risk comparison. For example, in men or women aged 50 years, the RR of hip fracture in those with osteoporosis compared to those without osteoporosis was 7.4 and 6.1, respectively. The RR of those at the threshold value for osteoporosis compared to those with an average value for BMD at that age was 6.6 and 4.6 in men and women, respectively. RRs were lower comparing those at the threshold value compared to the risk of the general population at that age (4.2 and 2.9, respectively). When RR was expressed in relation to the population risk rather than to the risk at the average value for BMD, RR decreased at all ages by 37%. Such adjustments are required for risk assessment in individuals and for the combined use of different risk factors. Because the average T score at each age decreased with age, the RR of hip fracture at any age decreased with advancing age in the presence of osteoporosis. The decrease in relative risk with age is, however, associated with an increase in absolute risk. Thus, for clinical use, the expression of absolute risks may be preferred to relative risks.
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| 4. |
- Lammi, Pirkko, et al.
(författare)
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Site-specific immunostaining for type X collagen in noncalcified articular cartilage of canine stifle knee joint.
- 2002
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Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 31:6, s. 690-696
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Tidskriftsartikel (refereegranskat)abstract
- Type X collagen is a short-chain collagen that is strongly expressed in hypertrophic chondrocytes. In this study, we used an immunohistochemical technique exploiting a prolonged hyaluronidase unmasking of type X collagen epitopes to show that type X collagen is not restricted to calcified cartilage, but is also present in normal canine noncalcified articular cartilage. A 30 degrees valgus angulation procedure of the right tibia was performed in 15 dogs at the age of 3 months, whereas their nonoperated sister dogs served as controls. Samples were collected 7 and 18 months after the surgery and immunostained for type X collagen. The deposition of type X collagen increased during maturation from age 43 weeks to 91 weeks. In the patella, most of the noncalcified cartilage stained for type X collagen, whereas, in the patellar surface of the femur, it was present mainly in the femoral groove close to cartilage surface. In femoral condyles, the staining localized mostly in the superficial cartilage on the lateral and medial sides, but not in the central weight-bearing area. In tibial condyles, type X collagen was often observed close to the cartilage surface in medial parts of the condyles, although staining could also be seen in the deep zone of the cartilage. Staining for type X collagen appeared strongest at sites where the birefringence of polarized light was lowest, suggesting a colocalization of type X collagen with the collagen fibril arcades in the intermediate zone. No significant difference in type X collagen immunostaining was observed in lesion-free articular cartilage between controls and dogs that underwent a 30 degrees valgus osteotomy. In osteoarthritic lesions, however, there was strong immunostaining for both type X collagen and collagenase-induced collagen cleavage products. The presence of type X collagen in the transitional zone of cartilage in the patella, femoropatellar groove, and in tibial cartilage uncovered by menisci suggests that it may involve a modification of collagen fibril arrangement at the site of collagen fibril arcades, perhaps providing additional support to the collagen network.
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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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