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Sökning: WFRF:(McCloskey Eugene)

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  • Borgström, Fredrik, et al. (författare)
  • Fragility fractures in Europe: burden, management and opportunities.
  • 2020
  • Ingår i: Archives of osteoporosis. - 1862-3514. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five countries of the European Union plus Sweden (EU6). In 2017, new fragility fractures in the EU6 are estimated at 2.7 million with an associated annual cost of €37.5 billion and a loss of 1.0 million quality-adjusted life years.Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fractures, which in turn, represent the main consequence of the disease. This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five EU countries and Sweden (designated the EU6).A series of metrics describing the burden and management of fragility fractures were defined by a scientific steering committee. A working group performed the data collection and analysis. Data were collected from current literature, available retrospective data and public sources. Different methods were applied (e.g. standard statistics and health economic modelling), where appropriate, to perform the analysis for each metric.Total fragility fractures in the EU6 are estimated to increase from 2.7 million in 2017 to 3.3 million in 2030; a 23% increase. The resulting annual fracture-related costs (€37.5 billion in 2017) are expected to increase by 27%. An estimated 1.0 million quality-adjusted life years (QALYs) were lost in 2017 due to fragility fractures. The current disability-adjusted life years (DALYs) per 1000 individuals age 50 years or more were estimated at 21 years, which is higher than the estimates for stroke or chronic obstructive pulmonary disease. The treatment gap (percentage of eligible individuals not receiving treatment with osteoporosis drugs) in the EU6 is estimated to be 73% for women and 63% for men; an increase of 17% since 2010. If all patients who fracture in the EU6 were enrolled into fracture liaison services, at least 19,000 fractures every year might be avoided.Fracture-related burden is expected to increase over the coming decades. Given the substantial treatment gap and proven cost-effectiveness of fracture prevention schemes such as fracture liaison services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are appropriately assessed and treated.
  • Estrada, Karol, et al. (författare)
  • Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
  • 2012
  • Ingår i: Nature genetics. - 1546-1718. ; 44:5, s. 491-501
  • 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 x 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 x 10(-4), Bonferroni corrected), of which six reached P < 5 x 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.
  • Giangregorio, Lora M, et al. (författare)
  • FRAX underestimates fracture risk in patients with diabetes
  • 2012
  • Ingår i: Journal of bone and mineral research. - 1523-4681. ; 27:2, s. 301-308
  • Tidskriftsartikel (refereegranskat)abstract
    • The study objective was to determine whether diabetes is a risk factor for incident hip or major osteoporotic fractures independent of FRAX. Men and women with diabetes (N = 3,518) and non-diabetics (N = 36,085) age ≥50 years at the time of BMD testing (1990-2007) were identified in a large clinical database from Manitoba, Canada. FRAX probabilities were calculated and fracture outcomes to 2008 were established via linkage with a population-based data repository. Multivariable Cox proportional hazards models were used to determine if diabetes was associated with incident hip fractures or major osteoporotic fractures after controlling for FRAX risk factors. Mean 10-year probabilities of fracture were similar between groups for major fractures (diabetic 11.1 ± 7.2 vs. non-diabetic 10.9 ± 7.3, p-value = 0.116) and hip fractures (diabetic 2.9 ± 4.4 vs. non-diabetic 2.8 ± 4.4, p-value = 0.400). Diabetes was a significant predictor of subsequent major osteoporotic fracture (HR 1.61 [95% CI; 1.42-1.83]) after controlling for age, sex, medication use, and FRAX risk factors including BMD. Similar results were seen after adjusting for FRAX probability directly (HR 1.59 [95% CI; 1.40-1.79]). Diabetes was also associated with significantly higher risk for hip fractures (p-value
  • Harvey, Nicholas C, et al. (författare)
  • Falls Predict Fractures Independently of FRAX Probability : : A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study
  • 2018
  • Ingår i: Journal of Bone and Mineral Research. - AMBMR. - 1523-4681. ; 33:3, s. 510-516
  • Tidskriftsartikel (refereegranskat)abstract
    • Although prior falls are a well-established predictor of future fracture, there is currently limited evidence regarding the specific value of falls history in fracture risk assessment relative to that of other clinical risk factors and bone mineral density (BMD) measurement. We therefore investigated, across the three Osteoporotic Fractures in Men (MrOS) Study cohorts, whether past falls predicted future fracture independently of FRAX and whether these associations varied with age and follow-up time. Elderly men were recruited from MrOS Sweden, Hong Kong, and USA. Baseline data included falls history (over the preceding 12 months), clinical risk factors, BMD at femoral neck, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the associations between falls, FRAX probability, and incident fracture, adjusting for age, time since baseline, and cohort in base models; further models were used to investigate interactions with age and follow-up time. Random-effects meta-analysis was used to synthesize the individual country associations. Information on falls and FRAX probability was available for 4365 men in USA (mean age 73.5 years; mean follow-up 10.8 years), 1823 men in Sweden (mean age 75.4 years; mean follow-up 8.7 years), and 1669 men in Hong Kong (mean age 72.4 years; mean follow-up 9.8 years). Rates of past falls were similar at 20%, 16%, and 15%, respectively. Across all cohorts, past falls predicted incident fracture at any site (hazard ratio [HR] = 1.69; 95% confidence interval [CI] 1.49, 1.90), major osteoporotic fracture (MOF) (HR = 1.56; 95% CI 1.33, 1.83), and hip fracture (HR = 1.61; 95% CI 1.27, 2.05). Relationships between past falls and incident fracture remained robust after adjustment for FRAX probability: adjusted HR (95% CI) any fracture: 1.63 (1.45, 1.83); MOF: 1.51 (1.32, 1.73); and hip: 1.54 (1.21, 1.95). In conclusion, past falls predicted incident fracture independently of FRAX probability, confirming the potential value of falls history in fracture risk assessment. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
  • Harvey, Nicholas C, et al. (författare)
  • Incidence of myocardial infarction and associated mortality varies by latitude and season: findings from a Swedish Registry Study.
  • 2019
  • Ingår i: Journal of public health (Oxford, England). - 1741-3850.
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether the incidence of death following myocardial infarction (MI) varied by season and latitude in the Swedish population.We studied deaths following MI from January 1987 to December 2009, using the Swedish National Cause of Death Register. County of residence was used to determine latitude and population density. An extension of Poisson regression was used to study the relationship between risk of death following MI with age, latitude, time (from 1987), population density and calendar days.Over the study period, there was a secular decrease in the incidence of MI-related death. In men, MI-related death incidence increased by 1.3% [95% confidence interval (CI) = 1.1-1.5] per degree of latitude (northwards). In women, MI-related death incidence increased by 0.6% (95% CI = 0.4-0.9) per degree of latitude. There was seasonal variation in the risk of MI-related death with peak values in the late winter and a nadir in the summer months in both the north and the south of Sweden. Findings were similar with incident MI as the outcome.The incidence of MI-related death varied markedly by season and latitude in Sweden, with summer months and more southerly latitude associated with lower rates than winter months and more northerly latitude.
  • Harvey, Nicholas C., et al. (författare)
  • Measures of Physical Performance and Muscle Strength as Predictors of Fracture Risk Independent of FRAX, Falls, and BMD : : A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study
  • 2018
  • Ingår i: Journal of Bone and Mineral Research. - AMBMR. - 0884-0431. ; 33:12, s. 2150-2157
  • Tidskriftsartikel (refereegranskat)abstract
    • Measures of muscle mass, strength, and function predict risk of incident fractures, but it is not known whether this risk information is additive to that from FRAX (fracture risk assessment tool) probability. In the Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, Hong Kong, United States), we investigated whether measures of physical performance/appendicular lean mass (ALM) by DXA predicted incident fractures in older men, independently of FRAX probability. Baseline information included falls history, clinical risk factors for falls and fractures, femoral neck aBMD, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the relationship between time for five chair stands, walking speed over a 6 m distance, grip strength, ALM adjusted for body size (ALM/height2), FRAX probability (major osteoporotic fracture [MOF]) with or without femoral neck aBMD, available in a subset of n = 7531), and incident MOF (hip, clinical vertebral, wrist, or proximal humerus). Associations were adjusted for age and time since baseline, and are reported as hazard ratios (HRs) for first incident fracture per SD increment in predictor using meta-analysis. 5660 men in the United States (mean age 73.5 years), 2764 men in Sweden (75.4 years), and 1987 men in Hong Kong (72.4 years) were studied. Mean follow-up time was 8.7 to 10.9 years. Greater time for five chair stands was associated with greater risk of MOF (HR 1.26; 95% CI, 1.19 to 1.34), whereas greater walking speed (HR 0.85; 95% CI, 0.79 to 0.90), grip strength (HR 0.77; 95% CI, 0.72 to 0.82), and ALM/height2 (HR 0.85; 95% CI, 0.80 to 0.90) were associated with lower risk of incident MOF. Associations remained largely similar after adjustment for FRAX, but associations between ALM/height2 and MOF were weakened (HR 0.92; 95% CI, 0.85 to 0.99). Inclusion of femoral neck aBMD markedly attenuated the association between ALM/height2 and MOF (HR 1.02; 95% CI, 0.96 to 1.10). Measures of physical performance predicted incident fractures independently of FRAX probability. Whilst the predictive value of ALM/height2 was substantially reduced by inclusion of aBMD requires further study, these findings support the consideration of physical performance in fracture risk assessment.
  • Johansson, Helena, 1981-, et al. (författare)
  • A meta-analysis of the association of fracture risk and body mass index in women.
  • 2014
  • Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 1523-4681. ; 29:1, s. 223-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.
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