| 11. |
- Leslie, William D, et al.
(författare)
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Selection of women aged 50-64 yr for bone density measurement.
- 2013
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Ingår i: Journal of Clinical Densitometry. - : Elsevier BV. - 1094-6950. ; 16:4, s. 570-8
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Tidskriftsartikel (refereegranskat)abstract
- The fracture risk assessment tool from the World Health Organization (FRAX(®)) estimates 10-yr major osteoporotic and hip fracture probabilities from multiple clinical risk factors and optionally femoral neck bone mineral density (BMD). FRAX without BMD has been proposed as a method to select postmenopausal women younger than 65yr for BMD measurement, but the efficiency of this strategy and its concordance with National Osteoporosis Foundation (NOF) treatment guidelines is unknown. The osteoporosis self-assessment test (OST) is another simple screening tool based on age and weight alone. A historical cohort of 18,315 women aged 50-64yr, drawn from the Manitoba Bone Density Program database, which contains clinical BMD results for the Province of Manitoba, Canada, was used to determine the performance of these screening tools in selecting postmenopausal women younger than 65yr for BMD testing. FRAX was closely aligned with indicators of high fracture risk (area under the receiver operating characteristic curve [AUROC]: 0.89), whereas OST was better for detecting women with osteoporotic BMD (AUROC: 0.72). The combination of major fracture probability 10% or higher from FRAX without BMD or OST less than 1 identified 42% of women for BMD testing, capturing 72% of women meeting any NOF treatment criteria (90% of women with NOF criteria for high risk from FRAX or prior fracture). The negative predictive value to exclude qualification for treatment under the NOF criteria was 90%. These data may help to inform an evidence-based approach for targeting BMD testing in postmenopausal women younger than 65yr under the NOF treatment guidelines.
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| 12. |
- McCloskey, Eugene, et al.
(författare)
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Fracture risk assessment
- 2012
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Ingår i: Clinical biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 45:12, s. 887-93
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Tidskriftsartikel (refereegranskat)abstract
- Having traditionally relied on measurements of bone mineral density, it is now established that the consideration of other risk variables improves the categorisation of fracture risk. Whereas several models are available, the FRAX models are the most extensively used. The approach uses easily obtained clinical risk factors to estimate 10 year fracture probability, with or without femoral neck bone mineral density (BMD), to enhance fracture risk prediction. It has been constructed and validated using primary data from population based cohorts around the world, including centres from North America, Europe, Asia and Australia. The FRAX® tool should not be considered as a gold standard, but rather as a platform technology on which to build as new validated risk indicators become available. Notwithstanding, the present models provide an aid to enhance patient assessment by the integration of clinical risk factors alone and/or in combination with BMD.
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| 13. |
- McCloskey, Eugene V, et al.
(författare)
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Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX.
- 2012
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 27:7, s. 1480-6
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Tidskriftsartikel (refereegranskat)abstract
- Denosumab has been shown to reduce the incidence of vertebral, nonvertebral, and hip fractures. The aim of the current study was to determine whether the antifracture efficacy of denosumab was dependent on baseline fracture probability assessed by FRAX. The primary data of the phase 3 FREEDOM study of the effects of denosumab in women with postmenopausal osteoporosis were used to compute country-specific probabilities using the FRAX tool (version 3.2). The outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. At baseline, the median 10-year probability of a major osteoporotic fracture (with bone mineral density) was approximately 15% and for hip fracture was approximately 5% in both groups. In the simplest model adjusted for age and fracture probability, treatment with denosumab over 3 years was associated with a 32% (95% confidence interval [CI] 20% to 42%) decrease in clinical osteoporotic fractures. Denosumab reduced fracture risk to a greater extent in those at moderate to high risk. For example, at 10% probability, denosumab decreased fracture risk by 11% (p = 0.629), whereas at 30% probability (90th percentile of study population) the reduction was 50% (p = 0.001). The reduction in fracture was independent of prior fracture, parental history of hip fracture, or secondary causes of osteoporosis. A low body mass index (BMI) was associated with greater efficacy. Denosumab significantly decreased the risk of clinical osteoporotic fractures in postmenopausal women. Overall, the efficacy of denosumab was greater in those at moderate to high risk of fracture as assessed by FRAX.
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| 14. |
- Moayyeri, Alireza, et al.
(författare)
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Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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| 15. |
- Odén, Anders, 1942, et al.
(författare)
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Assessing the impact of osteoporosis on the burden of hip fractures.
- 2013
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 92:1, s. 42-9
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Tidskriftsartikel (refereegranskat)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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| 16. |
- Targownik, Laura E, et al.
(författare)
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Inflammatory bowel disease and the risk of fracture after controlling for FRAX.
- 2013
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 28:5, s. 1007-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subjects with inflammatory bowel disease (IBD) are at increased risk for hip and other major osteoporotic fractures. However, previous analyses have not fully accounted for differences in bone mineral density (BMD) and other clinical factors that affect the risk of fracture. The World Health Organization Fracture Risk Assessment tool (FRAX®) can be used to predict the 10-year fracture riskfrom BMD and clinical risk factors. METHODS: A population based database containing clinical information on all IBD subjects in the province of Manitoba, Canada, was linked with the Manitoba Bone Mineral Density Database, which contains results of all dual X-ray absorptiometry (DXA) scans in the province. FRAX probabilities were calculated for all subjects aged50 years or more undergoing baseline DXA testing. Subjects were followed for occurrence of major osteoporotic fractures (MOF; hip, clinical spine, wrist, humerus). Cox proportional hazards models were used to determine whether IBD was independently predictive of MOF or hip fracture. RESULTS: After controlling for FRAX fracture probability computed with BMD, IBD was not associated with a significantly increased risk for MOF (HR 1.12, 95%CI 0.83-1.55) but was associated with an increased risk for hip fracture (HR 2.14, 95%CI 1.26-3.65).The addition of femoral neck T-score to FRAX probability without knowledge of BMD had a negligible effect on the estimated hazard ratios for IBD, suggesting that IBD mediates any effect on fracture risk independently of femoral neck BMD CONCLUSION: After controlling for FRAX probability, subjects with IBD are not at an increased risk for overall MOF, but may be at increased risk of hip fracture. © 2012 American Society for Bone and Mineral Research.
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| 17. |
- Zheng, Hou-Feng, et al.
(författare)
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WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk
- 2012
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Ingår i: PLoS genetics. - SAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE. - 1553-7404. ; 8:7, s. e1002745-
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)
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| 18. |
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