| 51. |
- Kaastad, T S, et al.
(författare)
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Effects of clodronate on cortical and trabecular bone in ovariectomized rats on a low calcium diet
- 1997
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 61:2, s. 158-164
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the contribution of a low calcium diet to the cortical and trabecular osteoporosis seen in ovariectomized rats after 7 weeks on a low calcium diet and to investigate the effects of the bisphosphonate clodronate on this development of osteoporosis. Thirty-six mature, female Wistar rats were randomized into four groups: Ovx-B (bisphosphonate) and Ovx-C (control) were ovariectomized, and Sham-Ca (low calcium) and Sham+Ca (normal calcium) were sham operated. The first three groups were fed a low calcium diet (0.01%) and Sham+Ca normal rat chow (Ca 1.1%). The Ovx-B received 10 mg/kg s.c. clodronate daily for nine weeks, and Ovx-C, Sham-Ca, and Sham+Ca received the same volumes of saline. Bone mineral turnover measured as 85Sr-uptake was increased in all low calcium groups compared to Sham+Ca. The Sham+Ca femora had higher dry weight and ash weight than the other groups, and Ovx-C had higher dry weight compared with Ovx-B and Sham-Ca. Calcium content was lower in both Ovx groups compared to both Sham groups. Magnesium was lower in all groups compared to Sham+Ca and higher in Ovx-B compared with Ovx-C. In the femoral shaft, Sham+Ca had significantly higher ultimate bending moment, energy absorption, and deflection compared to the other three groups. Ultimate bending moment was higher in Sham-Ca than in Ovx-C. Stiffness was increased in both Sham+Ca and Ovx-B compared to Ovx-C. The maximum stress in the femoral midshaft was higher in Sham+Ca than in the other groups, and higher in Ovx-B than in Ovx-C. Histomorphometry showed increased medullary area in all low calcium groups compared to Sham+Ca and larger cortical area in Sham+Ca and Ovx-B compared to Ovx-C. Compared to Sham+Ca the trabecular bone volume was decreased to 30% in Sham-Ca and to 9% in Ovx-C, but was unchanged in Ovx-B. The low calcium diet generally increased bone mineral turnover and reduced the tibial bone volume. Femoral changes led to a reduction of cortical fracture strength and maximal stress. Ovariectomy in addition to a low calcium diet reduced femoral strength even more. Daily injections of clodronate to ovariectomized rats on a low calcium diet increased femoral shaft stiffness and maximum stress, and clodronate preserved both trabecular and cortical tibial bone volume completely.
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| 52. |
- Kaastad, T S, et al.
(författare)
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Vitamin D deficiency and ovariectomy reduced the strength of the femoral neck in rats
- 2001
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 69:2, s. 102-108
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D (vit D) deficiency is common in the elderly, and the aim of this study was to investigate whether vit D deprivation in ovariectomized (ovx) and normal rats would reduce fracture strength. Forty mature female Wistar rats were randomized into four groups: two were ovariectomized (ovx) and two were sham-operated (sham). One ovx and one sham group were fed a vit D-deficient diet (Ovx-D and Sham-D), and the control groups were fed normal rat chow (Ovx and Sham) for 12 weeks. Vit D deficiency was substantiated after 12 weeks by undetectable serum concentrations of 25OHD in the Sham-D and Ovx-D groups. 85Sr activity was lower in Sham-D than in the other groups (P < 0.005). Tibial and femoral weights and lengths showed no differences. Distal tibial trabecular bone volume was reduced in both ovx groups compare with sham (P < 0.005). Bone mineral density (BMD) was higher in sham than in Sham-D and both ovx groups (P < 0.005). Femoral area moment of inertia increased and ultimate stress decreased in Ovx-D compared with ovx (P < 0.05). Other biomechanical properties of the femoral shafts did not differ significantly. The femoral neck was significantly weaker in Ovx-D than in the other groups. In conclusion, ovx decreased tibial trabecular bone volume and both ovx and vit D depletion reduced femoral BMD in rats. Vit D depletion reduced the ultimate stress in the femoral shaft, and the combined depletion of estrogen and vit D significantly reduced the fracture strength in the femoral neck. This fits well with clinical evidence of how postmenopausal status combined with vit D deficiency lead to an increased risk of hip fractures, making this animal model a possible tool for investigating measures to prevent such fractures.
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| 53. |
- Kanis, J A, et al.
(författare)
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Epidemiology of osteoporosis and fracture in men.
- 2004
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 75:2, s. 90-9
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Tidskriftsartikel (refereegranskat)
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| 54. |
- Kanis, John A, et al.
(författare)
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FRAX(®) with and without Bone Mineral Density
- 2012
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 90:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The use of FRAX, particularly in the absence of BMD, has been the subject of some debate and is the focus of this review. The clinical risk factors used in FRAX have high validity as judged from an evidence-based assessment and identify a risk that is responsive to pharmaceutical intervention. Moreover, treatment effects, with the possible exception of alendronate, are not dependent on baseline BMD and strongly suggest that FRAX identifies high-risk patients who respond to pharmaceutical interventions. In addition, the selection of high-risk individuals with FRAX, without knowledge of BMD, preferentially selects for low BMD. The prediction of fractures with the use of clinical risk factors alone in FRAX is comparable to the use of BMD alone to predict fractures and is suitable, therefore, in the many countries where DXA facilities are sparse. In countries where access to BMD is greater, FRAX can be used without BMD in the majority of cases and BMD tests reserved for those close to a probability-based intervention threshold. Whereas the efficacy for agents to reduce fracture risk has not been tested prospectively in randomized controlled trials in patients selected on the basis of FRAX probabilities, there is compelling evidence that FRAX with or without the use of BMD provides a well-validated instrument for targeting patients most likely to benefit from an intervention.
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| 55. |
- Karlsson, Magnus, et al.
(författare)
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Changes in bone mineral, lean body mass and fat content as measured by dual energy X-ray absorptiometry: a longitudinal study
- 2000
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 66:2, s. 97-99
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) and soft tissue composition were measured by dual energy X-ray absorptiometry (DXA) 3-4 years apart in 273 men and women aged 23-90. We found different rates of BMD loss in different skeletal regions. There were also different rates of BMD loss in different regions within the hip. Average rates of loss for male subjects 50 years of age and above for BMD total body were 0.1%/year and for femoral neck 1.5%/year, whereas lumbar spine (L2-L4) increased by 0.4%/year. Average rates of loss for female subjects 50 years of age and above for BMD total body were 0.0%/year, femoral neck 0.9%/year, and lumbar spine (L2-L4) 0.1%/year.
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| 56. |
- Karlsson, Magnus, et al.
(författare)
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Individuals who sustain nonosteoporotic fractures continue to also sustain fragility fractures
- 1993
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Ingår i: Calcified Tissue International. - 1432-0827. ; 53:4, s. 229-231
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Tidskriftsartikel (refereegranskat)abstract
- This retrospective case control study was done in order to investigate whether patients who sustain a "nonosteoporotic fracture" early in life also continue to sustain fragility fractures later in life. All patients who had been treated at the Department of Orthopedics in Malmo with a tibial shaft fracture from 1949 to 1963 (n = 767) or an ankle fracture from 1961 to 1965 (n = 786) were included in this study. At the time of follow-up in 1992, 231 of the patients who sustained a tibial shaft fracture and 260 of the patients who sustained an ankle fracture were still living in the city of Malmo. Objective registration was done of all subsequent fractures that these former patients had sustained. Comparison was done with corresponding data from double numbers of age- and sex-matched controls who at that time (1950s and 1960s) had no such fractures. At the time of the fracture as well as today, the controls were living in the area of Malmo. Individuals with earlier tibial or ankle fractures had an increased incidence of fractures generally classified as fragility fractures. There was no difference in this respect between men and women, nor whether the initial fracture had been diaphyseal or metaphyseal. We conclude that sustenance of fractures early in life may serve as a predictor for fragility fractures later in life.
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| 57. |
- Karlsson, M K, et al.
(författare)
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Indicators of bone formation in weight lifters
- 1995
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Ingår i: Calcified Tissue International. - 1432-0827. ; 56:3, s. 177-180
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity has been suggested to be one of the determinants of bone turnover and to prevent age-related bone loss. To examine this we measured the serum levels of osteocalcin (bone Gla-protein, BGP), C-terminal procollagen peptide (PICP), serum alkaline phosphatase, bone-specific alkaline phosphatase, and S-calcium as indices of bone formation in 19 actively performing and 15 ex-lifters. All were nationally or internationally ranked male athletes. Their values were compared with those from 38 age- and gender-matched controls. Actively performing weight lifters had 35% higher (P < 0.05) serum concentration of osteocalcin than the controls. The ex-lifters did not differ from the age-matched controls. Also serum calcium was elevated in active lifters (6%) (P < 0.01) but not in ex-lifters. No difference was found for serum-ALP, B-ALP, or PICP in either of the groups. Our study indicates that in addition to an already documented and well-known higher bone mineral density in heavily exercising athletes, they have an indication of higher bone formation as measured by biochemical markers. In athletes who have retired from competitional training, however, the bone formation does not differ from that of more sedentary controls.
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| 58. |
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| 59. |
- Kharazmi, Mohammad, et al.
(författare)
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A Genome-Wide Association Study of Bisphosphonate-Associated Atypical Femoral Fracture
- 2019
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Ingår i: Calcified Tissue International. - : SPRINGER. - 0171-967X .- 1432-0827. ; 105:1, s. 51-67
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Tidskriftsartikel (refereegranskat)abstract
- Atypical femoral fracture is a well-documented adverse reaction to bisphosphonates. It is strongly related to duration of bisphosphonate use, and the risk declines rapidly after drug withdrawal. The mechanism behind bisphosphonate-associated atypical femoral fracture is unclear, but a genetic predisposition has been suggested. With the aim to identify common genetic variants that could be used for preemptive genetic testing, we performed a genome-wide association study. Cases were recruited mainly through reports of adverse drug reactions sent to the Swedish Medical Products Agency on a nation-wide basis. We compared atypical femoral fracture cases (n=51) with population-based controls (n=4891), and to reduce the possibility of confounding by indication, we also compared with bisphosphonate-treated controls without a current diagnosis of cancer (n=324). The total number of single-nucleotide polymorphisms after imputation was 7,585,874. A genome-wide significance threshold of p<5x10(-8) was used to correct for multiple testing. In addition, we performed candidate gene analyses for a panel of 29 genes previously implicated in atypical femoral fractures (significance threshold of p<5.7x10(-6)). Compared with population controls, bisphosphonate-associated atypical femoral fracture was associated with four isolated, uncommon single-nucleotide polymorphisms. When cases were compared with bisphosphonate-treated controls, no statistically significant genome-wide association remained. We conclude that the detected associations were either false positives or related to the underlying disease, i.e., treatment indication. Furthermore, there was no significant association with single-nucleotide polymorphisms in the 29 candidate genes. In conclusion, this study found no evidence of a common genetic predisposition for bisphosphonate-associated atypical femoral fracture. Further studies of larger sample size to identify possible weakly associated genetic traits, as well as whole exome or whole-genome sequencing studies to identify possible rare genetic variation conferring a risk are warranted.
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| 60. |
- Kindmark, Andreas, et al.
(författare)
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Inhibitory effects of 9-cis and all-trans retinoic acid on 1,25(OH)2 vitamin D3 induced bone resorption
- 1995
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Ingår i: Calcified Tissue International. - 0171-967X .- 1432-0827. ; 57:3, s. 242-244
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Tidskriftsartikel (refereegranskat)abstract
- The effects of retinoic acid (RA), and calcitriol are mediated by specific nuclear receptors (RARs and VDR, respectively). Induction of RAR and VDR responsive elements in target genes requires a cofactor, the retinoid-X-receptor (RXR), with its ligand 9-cis RA. We have previously demonstrated the expression of RARs and RXRs in osteoblasts, and herein investigated the effects of the retinoids all-trans RA and 9-cis RA alone and combined with calcitriol on bone resorption in vitro, measured by 45Ca-release from prelabeled neonatal mouse calvarial bones. All-trans RA and 9-cis RA were powerful stimulators of bone resorption and essentially equipotent. At threshold concentrations (1 nM) both 9-cis RA and at-RA markedly inhibited the resorption induced by calcitriol (1 pM). The findings are compatible with a physiological role for retinoids in bone metabolism.
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