| 1. |
- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 2. |
- Kanis, J A, et al.
(författare)
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Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.
- 2023
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Nature. - 1433-2965 .- 0937-941X. ; 34:12, s. 2027-2045
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Tidskriftsartikel (refereegranskat)abstract
- A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX.The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD).We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted β-coefficients.A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination.A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.
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| 3. |
- Vandenput, L., et al.
(författare)
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A meta-analysis of previous falls and subsequent fracture risk in cohort studies
- 2024
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Ingår i: Osteoporosis International. - : Springer Nature. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
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Tidskriftsartikel (refereegranskat)abstract
- Summary: The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. Introduction: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). Methods: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. Results: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95% CI 1.20–1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. Conclusions: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.
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| 4. |
- Vandenput, Liesbeth, 1974, et al.
(författare)
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Update of the fracture risk prediction tool FRAX : a systematic review of potential cohorts and analysis plan
- 2022
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 33:10, s. 2103-2136
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Forskningsöversikt (refereegranskat)abstract
- Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures.Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors.Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible.Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed.Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).
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| 5. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 6. |
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| 7. |
- Johansson, H, et al.
(författare)
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UTILITY LOSS AFTER A SENTINEL FRACTURE
- 2018
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Ingår i: OSTEOPOROSIS INTERNATIONAL. - 0937-941X. ; 29, s. S72-S73
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Vandenput, Liesbeth, et al.
(författare)
-
A meta-analysis of previous falls and subsequent fracture risk in cohort studies
- 2024
-
Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
-
Tidskriftsartikel (refereegranskat)abstract
- SummaryThe relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm.IntroductionPrevious falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD).MethodsThe resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.ResultsFalls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95% CI 1.20–1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men.ConclusionsA previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.
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| 9. |
- Jonsson, Brynjolfur, et al.
(författare)
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Fracture rate in a population-based sample of men in Reykjavik
- 2004
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Ingår i: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 75:2, s. 195-200
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Tidskriftsartikel (refereegranskat)abstract
- The population-based Reykjavik Heart Study, started in 1967, aims at finding and evaluating risk factors for cardiovascular diseases. It included 4,137 men born between 1907 and 1934 and we examined all fractures recorded in these subjects from January 1977 until the end of December 2000, or death. Their mean age at the start of this study was 54 (42-69) years and the mean follow-up time 19 years. We examined the patients' records, including those from the Radiological Departments in all Reykjavik hospitals and the only out-patient accident clinic in Reykjavik. Old fractures and those caused by a malignancy were excluded. The intensity of the trauma was estimated from E-numbers. Altogether 1,531 fractures were recorded in 939 (23%) persons. A low-energy trauma caused 53% of all fractures. 612 had a single fracture during this period. 323 had two or more fractures-a 53% risk of sustaining additional fractures. The fracture incidence increased by 40% in each 10-year period.. Fractures of the ribs were commonest (246), followed by those of the hand (241). 135 were hip fractures, 75% caused by low-energy trauma. The fracture rate was 20 per 1000 persons year-i.e., similar to that in other studies.
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| 10. |
- Kanis, J. A., et al.
(författare)
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Adjusting conventional FRAX estimates of fracture probability according to the number of prior fractures
- 2022
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33:12, s. 2507-2515
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Tidskriftsartikel (refereegranskat)abstract
- The risk of a recurrent fragility fracture is high following a first fracture and higher still with more than one prior fracture. This study provides adjustments to FRAX-based fracture probabilities accounting for the number of prior fractures. Introduction Prior fractures increase subsequent fracture risk. The aim of this study was to quantify the effect of the number of prior fractures on the 10-year probability of fracture determined with FRAX (R). Methods The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Ten-year probabilities of hip fracture and major osteoporotic fracture (MOF) were determined according to the number of prior osteoporotic fractures over a 20-year interval from the hazards of death and fracture. Fracture probabilities were also computed for a prior osteoporotic fracture irrespective of the number of previous fractures. The probability ratios provided adjustments to conventional FRAX estimates of fracture probability according to the number of prior fractures. Results Probability ratios to adjust 10-year FRAX probabilities of a hip fracture and MOF increased with the number of prior fractures but decreased with age in both men and women. Probability ratios were similar in men and women and for hip fracture and MOF. Mean probability ratios according to the number of prior fractures for all scenarios were 0.95, 1.08, 1.21 and 1.35, for 1,2, 3 and 4 or more prior fractures, respectively. Thus, a simple rule of thumb is to downward adjust FRAX-based fracture probabilities by 5% in the presence of a single prior fracture and to uplift probabilities by 10, 20 and 30% with a history of 2, 3 and 4 or more prior fractures, respectively. Conclusion The probability ratios provide adjustments to conventional FRAX estimates of fracture probability according to the number of prior fractures.
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| 11. |
- Kanis, J. A., et al.
(författare)
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Adjusting conventional FRAX estimates of fracture probability according to the recency of sentinel fractures
- 2020
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 31, s. 1817-1828
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Tidskriftsartikel (refereegranskat)abstract
- The risk of a recurrent fragility fracture is particularly high immediately following the fracture. This study provides adjustments to FRAX-based fracture probabilities accounting for the site of a recent fracture. Introduction The recency of prior fractures affects subsequent fracture risk. The aim of this study was to quantify the effect of a recent sentinel fracture, by site, on the 10-year probability of fracture determined with FRAX. Methods The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Fracture probabilities were determined after a sentinel fracture (humeral, clinical vertebral, forearm and hip fracture) from the hazards of death and fracture. Fracture probabilities were computed on the one hand for sentinel fractures occurring within the previous 2 years and on the other hand, probabilities for a prior osteoporotic fracture irrespective of recency. The probability ratios provided adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures. Results Probability ratios to adjust 10-year FRAX probabilities of a major osteoporotic fracture for recent sentinel fractures were age dependent, decreasing with age in both men and women. Probability ratios varied according to the site of sentinel fracture with higher ratios for hip and vertebral fracture than for humerus or forearm fracture. Probability ratios to adjust 10-year FRAX probabilities of a hip fracture for recent sentinel fractures were also age dependent, decreasing with age in both men and women with the exception of forearm fractures. Conclusion The probability ratios provide adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures.
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| 12. |
- Kanis, J. A., et al.
(författare)
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The effect on subsequent fracture risk of age, sex, and prior fracture site by recency of prior fracture
- 2021
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 32:8, s. 1547-1555
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Tidskriftsartikel (refereegranskat)abstract
- The risk of a recurrent fragility fracture varies by age and sex, as by site and recency of sentinel fracture. Introduction The recency of prior fractures affects subsequent fracture risk. Variable recency may obscure other factors that affect subsequent fracture risk. The aim of this study was to quantify the effect of a sentinel fracture by site, age, and sex where the recency was held constant. Methods The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Fracture incidence was compared to that of the general population determined at fixed times after a sentinel fracture (humeral, clinical vertebral, forearm, hip, and minor fractures). Outcome fractures comprised a major osteoporotic fracture and hip fracture. Results Sentinel osteoporotic fractures were identified in 9504 men and women. Of these, 3616 individuals sustained a major osteoporotic fracture as the first subsequent fracture, of whom 1799 sustained a hip fracture. Hazard ratios for prior fracture were consistently higher in men than in women and decreased progressively with age. Hazard ratios varied according to the site of sentinel fracture with higher ratios for hip and vertebral fracture than for humerus, forearm, or minor osteoporotic fracture. Conclusion The risk of a recurrent fragility fracture varies by age, sex, and site of sentinel fracture when recency is held constant.
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| 13. |
- Kanis, J. A., et al.
(författare)
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The use of 2-, 5-, and 10-year probabilities to characterize fracture risk after a recent sentinel fracture
- 2021
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 32, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- The increase in fracture risk associated with a recent fragility fracture is more appropriately captured using a 10-year fracture probability than 2- or 5-year probabilities. Introduction The recency of prior fractures affects subsequent fracture risk. The aim of this study was to quantify the effect of a recent sentinel fracture, by site, on the 2-, 5-, and 10-year probability of fracture. Methods The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Fracture probabilities were determined after a sentinel fracture (humeral, clinical vertebral, forearm and hip fracture) occurring within the previous 2 years and probabilities for a prior osteoporotic fracture irrespective of recency. The probability ratios were used to adjust fracture probabilities over a 2-, 5-, and 10-year time horizon. Results As expected, probabilities decreased with decreasing time horizon. Probability ratios varied according to age and the site of sentinel fracture. Probability ratios to adjust for a prior fracture within the previous 2 years were higher the shorter the time horizon, but the absolute increases in fracture probabilities were much reduced. Thus, fracture probabilities were substantially lower with time horizons less than 10 years. Conclusion The 10-year probability of fractures is the appropriate metric to capture the impact of the recency of sentinel fractures. The probability ratios provide adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures, adjustments which can readily inform clinical decision-making.
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| 14. |
- Kanis, JA, et al.
(författare)
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Characteristics of recurrent fractures
- 2018
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965. ; 29:8, s. 1747-1757
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Keyak, J. H., et al.
(författare)
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Effect of finite element model loading condition on fracture risk assessment in men and women: The AGES-Reykjavik study
- 2013
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 57:1, s. 18-29
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Tidskriftsartikel (refereegranskat)abstract
- Proximal femoral (hip) strength computed by subject-specific CT scan-based finite element (FE) models has been explored as an improved measure for identifying subjects at risk of hip fracture. However, to our knowledge, no published study has reported the effect of loading condition on the association between incident hip fracture and hip strength. In the present study, we performed a nested age- and sex-matched case-control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort Baseline (pre-fracture) quantitative CT (QCT) scans of 5500 older male and female subjects were obtained. During 4-7 years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as controls from a pool of age- and sex-matched subjects. From the QCT data, FE models employing nonlinear material properties computed FE-strength of the left hip of each subject in loading from a fall onto the posterolateral (F-PL), posterior (F-P) and lateral (F-L) aspects of the greater trochanter (patent pending). For comparison, FE strength in stance loading (F-Stance) and total femur areal bone mineral density (aBMD) were also computed. For all loading conditions, the reductions in strength associated with fracture in men were more than twice those in women (p <= 0.01). For fall loading specifically, posterolateral loading in men and posterior loading in women were most strongly associated with incident hip fracture. After adjusting for aBMD, the association between F-P and fracture in women fell short of statistical significance (p = 0.08), indicating that FE strength provides little advantage over aBMD for identifying female hip fracture subjects. However, in men, after controlling for aBMD, F-PL was 424 N (11%) less in subjects with fractures than in controls (p = 0.003). Thus, in men, FE models of posterolateral loading include information about incident hip fracture beyond that in aBMD. (c) 2013 Elsevier Inc. All rights reserved.
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| 16. |
- Keyak, J. H., et al.
(författare)
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Male-female differences in the association between incident hip fracture and proximal femoral strength: A finite element analysis study
- 2011
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 48:6, s. 1239-1245
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Tidskriftsartikel (refereegranskat)abstract
- Hip fracture risk is usually evaluated using dual energy X-ray absorptiometry (DXA) or quantitative computed tomography (QCT) which provide surrogate measures for proximal femoral strength. However, proximal femoral strength can best be estimated explicitly by combining QCT with finite element (FE) analysis. To evaluate this technique for predicting hip fracture in older men and women, we performed a nested age- and sex-matched case-control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Baseline (pre-fracture) QCT scans of 5500 subjects were obtained. During 4-7 years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as age- and sex-matched controls. FE-strength of the left hip of each subject for stance (F-Stance) and posterolateral fall (F-Fall) loading, and total femur areal bone mineral density (aBMD) were computed from the QCT data. F-Stance and F-Fall in incident hip fracture subjects were 13%-25% less than in control subjects (p <= 0.006) after controlling for demographic parameters. The difference between FE strengths of fracture and control subjects was disproportionately greater ill men (stance, 22%; fall, 25%) than in women (stance, 13%; fall, 18%) (p <= 0.033), considering that Fstar,ce and FFall in fracture subjects were greater in men than in women ( p < 0.001). For men, F-Stance was associated with hip fracture after accounting for aBMD (p = 0.013). These data indicate that F-Stance provides information about fracture risk that is beyond that provided by aBMD (p = 0.013). These findings support further exploration of possible sex differences in the predictors of hip fracture and of sex-specific strategies for using FE analysis to manage osteoporosis. (C) 2011 Elsevier Inc. All rights reserved.
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| 17. |
- Lang, T. F., et al.
(författare)
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Age-related loss of proximal femoral strength in elderly men and women: The Age Gene/Environment Susceptibility Study - Reykjavik
- 2012
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 50:3, s. 743-748
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Tidskriftsartikel (refereegranskat)abstract
- The risk of hip fracture rises rapidly with age, and is particularly high in women. This increase in fracture risk reflects both the age-related change in the risk of falling and decrements in the strength of the proximal femur. To better understand the extent to which proximal femoral density, structure and strength change with age as a function of gender, we have carried out a longitudinal analysis of proximal femoral volumetric quantitative computed tomographic (vQCT) images in men and women, analyzing changes in trabecular and cortical bone properties, and using subject-specific finite element modeling (FEM) to estimate changes in bone strength. In the AGES-Reykjavik Study vQCT scans of the hip were performed at a baseline visit in 2002-2006 and at a second visit 5.05 +/- 0.25 years later. From these, 223 subjects (111 men, 112 women, aged 68-87 years) were randomly selected. The subjects were evaluated for longitudinal changes in three bone variables assessed in a region similar to the total femur region quantified by DXA: areal bone mineral density (aBMD), trabecular volumetric bone mineral density (tBMD) and the ratio of cortical to total tissue volume (cvol/ivol). They were also evaluated for changes in bone strength using FEM models of the left proximal femur. Models were analyzed under single-limb stance loading (F-Stance), which approximates normal physiologic loading of the hip, as well as a load approximating a fall onto the posterolateral aspect of the greater trochanter (F-Fall). We computed five-year absolute and percentage changes in aBmD, tBMD, cvol/ivol, F-Fall and F-Stance. The Mann-Whitney Test was employed to compare changes in bone variables between genders and the Wilcoxon Signed Rank Test was used to compare changes in bone strength between loading conditions. Multiple (linear) regression was employed to determine the association of changes in F-Fall and F-Stance with baseline age and five-year weight loss. Both men and women showed declines in indices of proximal femoral density and structure (aBMD: men -3.9 +/- 6.0%, women -6.1 +/- 6.2%; tBMD: men -14.8 +/- 20.3%, women -23.9 +/- 26.8%; cvol/ivol: men -2.6 +/- 4.6%, women -4.7 +/- 4.8%, gender difference: p<0.001). Both men and women lost bone strength in each loading condition (F-Stance: men -4.2 +/- 9.9%, women -8.3 +/- 8.5%; F-Fall: men -7.0 +/- 15.7%, women -12.8 +/- 13.2%; all changes from baseline p<0.0001). The gender difference in bone strength loss was statistically significant in both loading conditions (p<0.001 for F-Stance and P<0.01 for F-Fall) and F-Fall, was lost at a higher rate than F-Stance in men (p<0.01) and women (p<0.0001). The gender difference in strength loss was statistically significant after adjustment for baseline age and weight loss in both loading conditions (p<0.01). In these multi-linear models, men showed increasing rates of bone loss with increasing age (F-Fall: p=0.002; F-Stance; p=0.03), and women showed increasing bone strength loss with higher degrees of weight loss (F-Stance: p=0.003). The higher loss of F-Fall compared to F-Stance supports previous findings in animal and human studies that the sub-volumes of bone stressed under normal physiologic loading are relatively better protected in aging. The gender difference in hip bone strength loss is consistent with the higher incidence of hip fractureamong elderly women. (C) 2011 Elsevier Inc. All rights reserved.
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| 18. |
- 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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| 19. |
- Nielson, Carrie M., et al.
(författare)
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Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 31:12, s. 2085-2097
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n=15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n=21,701) and clinical vertebral fracture (n=5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF]=3%) was associated with higher vBMD (β=0.22, p=1.9×10-8) and decreased risk of radiographic vertebral fracture (odds ratio [OR]=0.75; false discovery rate [FDR] p=0.01). In 1p36.12, rs12742784 (MAF=21%) was associated with higher vBMD (β=0.09, p=1.2×10-10) and decreased risk of clinical vertebral fracture (OR=0.82; FDR p=7.4×10-4). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β=0.28, FDR p=0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β=0.12, FDR p=1.7×10-3, functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence.
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| 20. |
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| 21. |
- Siggeirsdottir, K., et al.
(författare)
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Epidemiology of fractures in Iceland and secular trends in major osteoporotic fractures 1989-2008
- 2014
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 25:1, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of the most common fracture types in Iceland is reported based on individual data from the Reykjavik Study 1967-2008. Time trend is reported for the major osteoporotic fractures (MOS) 1989-2008. This study aims to assess the incidence of all fractures in Iceland, with emphasis on the rate of hip fractures, and compare the incidence with other populations as well as examine the secular changes. Individuals from the prospective population-based cohort Reykjavik Study were examined between 1967 and 2008 (follow-up 26.5 years), which consisted of 9,116 men and 9,756 women born in 1907-1935, with age range 31-81 years. First fracture incidence was estimated using life table methods with age as the timescale. Fracture rate increased proportionally with age between the sexes for vertebral and proximal humerus but disproportionally for hip and distal forearm fractures. The ratio of first fracture incidence between the sexes varied considerably by site: 2.65 for hip fractures and the highest for distal forearm fractures at 4.83. By the age of 75, 36.7 % of women and 21 % of men had sustained a fracture, taking into account competing risk of death. The incidence of hip fractures was similar to results previously published from USA, Sweden, Norway, and Scotland. The incidence of MOS fractures in both sexes decreased over the last decade, except hip fractures in men, which remained unchanged, as reflected in the women/men ratio for the hip, which changed from 2.6 to 1.7. This study adds information to scarce knowledge on the relative fracture incidence of different fractures. The incidence of MOS fractures increased in the latter part of the last century in both sexes and declined during the last decade, less dramatically for men. This information is important for planning health resources.
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| 22. |
- Siggeirsdottir, K, et al.
(författare)
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Short hospital stay augmented with education and home-based rehabilitation improves function and quality of life after hip replacement - Randomized study of 50 patients with 6 months of follow-up
- 2005
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 76:4, s. 555-562
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Tidskriftsartikel (refereegranskat)abstract
- Background Because of current cost restrictions, we studied the effect of a shorter hospital stay on function, pain and quality of life (QOL) after total hip replacement (THR). Patients and methods 50 patients from two hospitals were randomized into a study group (SG) of 27 patients receiving preoperative and postoperative education programs, as well as home visits from an outpatient team, and a control group (CG) of 23 patients receiving "conventional" rehabilitation often augmented by a stay at a rehabilitation center. Results Mean hospital stay was shorter for the SG than for the CG (6.4 days and 10 days, respectively; p < 0.001). During the 6-month study period, there were 9 non-fatal complications in the SG and 12 in the CG (p = 0.3). The difference in Oxford Hip Score between the groups was not statistically significant before the operation, but was better for the SG at 2 months (p = 0.03) and this difference remained more or less constant throughout the study. The overall score from the Nottingham Health Profile indicated a better QOL in the SG. Interpretation Our preoperative education program, followed by postoperative home-based rehabilitation, appears to be safer and more effective in improving function and QOL after THR than conventional treatment.
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| 23. |
- Siggeirsdottir, K., et al.
(författare)
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The incidence of a first major osteoporotic fracture in Iceland and implications for FRAX
- 2014
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 25:10, s. 2445-2451
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Tidskriftsartikel (refereegranskat)abstract
- Based on an extensive cohort study over 25 years, the present study supports the assumption that major osteoporotic fractures can be reasonably predicted from hip fracture rates. The construct for FRAX models depends on algorithms to adjust for double counting of fracture outcomes in some models and in others, to estimate the incidence of a major fracture from hip fracture rates. The aim of the present study was to test the validity of these algorithms in a large prospective cohort. The incidence of hip, clinical spine, distal forearm, and humerus fracture was determined in the prospective and ongoing population-based Reykjavik Study with follow up of 257,001 person-years. The incidence of a first major fracture was compared with the correction factors used in FRAX to adjust the incidence of several fracture outcomes for double counting. In addition, the incidence of a major osteoporotic fracture estimated from the Icelandic hip fracture rates was compared with the Malmo ratios used in FRAX. The adjustments necessary to account for multiple fracture outcomes were similar to those previously derived from Sweden. Additionally, incidence of a first major osteoporotic fracture was similar to that derived for FRAX models. The findings of the present study support the algorithms used in FRAX to estimate the incidence of a first major fracture and the predictive value of hip fracture for other major fractures.
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| 24. |
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| 25. |
- Siggeirsdottir, K, et al.
(författare)
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The timed 'Up & Go' is dependent on chair type
- 2002
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Ingår i: Clinical Rehabilitation. - : SAGE Publications. - 1477-0873 .- 0269-2155. ; 16:6, s. 609-616
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The timed 'Up & Go' (TUG) is a performance test identifying problems in functional mobility. More knowledge on how the type of chair used influences test results is needed. Objective: To investigate inter-rater agreement on the time score and to assess if chair type used influenced the performance of the test. Setting: (1) Inter-rater agreement investigation on the time score was carried out with elderly individuals living in a retirement home (n = 31). (2) Four types of chairs were tested on elderly individuals in three different health care centres (n = 100). Results: The two observers were close in timing (mean difference = 0.04 s). From a reference chair the median time for TUG was 15.7 s compared with 16.9 s from a chair with a low seat (p < 0.001). It was significantly more difficult to stand up from a chair without armrests (p < 0.001), and from the lowest chair (p < 0.001), which was also the only chair difficult to sit down on (p = 0.02). Conclusion: The inter-rater agreement of the time scoring of the TUG has been confirmed. Test performance is dependent on chair type; chairs with armrests and a seating height of 44-47 cm should be used. Clinicians must follow standard procedures and equipment when using the test or else risk invalidating test findings.
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