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1.
  • Albertsson, Daniel M, 1957, et al. (author)
  • Hip and fragility fracture prediction by 4-item clinical risk score and mobile heel BMD: a women cohort study
  • 2010
  • In: BMC Musculosceletal disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 11
  • Journal article (peer-reviewed)abstract
    • Background One in four Swedish women suffers a hip fracture yielding high morbidity and mortality. We wanted to revalidate a 4-item clinical risk score and evaluate a portable heel bone mineral density (BMD) technique regarding hip and fragility fracture risk among elderly women. Methods In a population-based prospective cohort study we used clinical risk factors from a baseline questionnaire and heel BMD to predict a two-year hip and fragility fracture outcome for women, in a fracture preventive program. Calcaneal heel BMD was measured by portable dual X-ray laser absorptiometry (DXL) and compared to hip BMD, measured with stationary dual X-ray absorptiometry (DXA) technique. Results Seven women suffered hip fracture and 14 women fragility fracture/s (at hip, radius, humerus and pelvis) among 285 women; 60% having heel BMD ≤ -2.5 SD. The 4-item FRAMO (Fracture and Mortality) Index combined the clinical risk factors age ≥80 years, weight <60 kg, prior fragility fracture, and impaired rise-up ability. Women having 2-4 risk factors showed odds ratio (OR) for hip fracture of 5.9 and fragility fracture of 4.4. High risk group hip fracture risk was 2.8% annually compared to 0.5% for the low risk majority (69%). Heel BMD showed hip fracture OR of 3.1 and fragility fracture OR of 2.6 per SD decrease. For 30 DXA assessed participants mean hip BMD at -2.5 SD level corresponded to a lower BMD at the heel. Five of seven hip fractures occurred within a small risk group of 32 women, identified by high FRAMO Index + prior fragility fracture + heel T-score ≤-3.5 SD. Conclusions In a follow-up study we identified high risk groups for hip and fragility fracture with our plain 4-item risk model. Increased fracture risk was also related to decreasing heel BMD in calcaneal bone, measured with a mobile DXL technique. A combination of high FRAMO Index, prior fragility fracture, and very low BMD restricted the high risk group to 11%, among whom most hip fractures occurred (71%). These practical screening methods could eventually reduce hip fracture incidence by concentrating preventive resources to high fracture risk women.
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2.
  • Albertsson, Daniel M, 1957, et al. (author)
  • Risk group for hip fracture in elderly women identified by primary care questionnaire--clinical implications.
  • 2006
  • In: Upsala journal of medical sciences. - 0300-9734. ; 111:2, s. 179-87
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Every fourth Swedish woman suffers hip fracture during life-time. Several methods for fall and fracture prevention are known. In this study we identify women at high hip fracture risk in a primary care population, describing their needs for possible fracture prevention as well. METHODS: Cross-sectional questionnaire study for self-assessment by randomly chosen elderly women (n=100) over 70 years of age in a Primary health Care district at 1998. Questionnaire was designed from previous validated study. Follow-up study after three years performed at 2001. RESULTS: Response rate was 92% (n=92, mean age 78) and 90% (n=83) answered the main 40 questions. 30% had at least two of four major risk factors for hip fracture; age over 80 years, body weight below 60 kg, recent fall and previous fragility fracture. The recall ability for at least two of these four risk factors was 93% in follow-up study after three years (relative risk = 8.0 with 95% confidence interval 3.5 to 18). 34% of the women had experienced any fracture since the age of 50. Only 22% of the women with previous fragility fracture had any pharmacological treatment for osteoporosis. 26% had falls in the preceding 12 months, mainly at home. Needs for fracture prevention were found in 34% (27 women). CONCLUSIONS: Age, weight, recent falls or previous fragility fracture were common and important clinical risk factors for hip fracture with good recall ability after three years. By using this questionnaire in a Primary health Care district we identified women at high fracture risk. Needs for fracture prevention were observed for one third.
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3.
  • Albertsson, Daniel M, 1957, et al. (author)
  • Validation of a 4-item score predicting hip fracture and mortality risk among elderly women.
  • 2007
  • In: Annals of family medicine. - : Annals of Family Medicine. - 1544-1717 .- 1544-1709. ; 5:1, s. 48-56
  • Journal article (peer-reviewed)abstract
    • PURPOSE: One in 4 Swedish women experiences a hip fracture, an event that has high concomitant morbidity and mortality. We developed and validated a clinical predictor of fracture and mortality risk, the Fracture and Mortality (FRAMO) Index. METHODS: This was a population-based prospective cohort study with a baseline questionnaire and 2-year outcomes of hip fracture, fragility fracture, and death. The questionnaire was sent to 1,498 women aged 70 years or older in 3 rural populations, asking them about their age, weight, height, mobility, previous fractures, smoking, medication use, and housing. Some women were also asked about previous vertebral radiographs. We defined 2 risk models before outcome data collection and subsequently renamed 1 model (age =80 years, weight <60 kg, previous fragility fracture, and the need to use arms to rise from the sitting position) the FRAMO Index. We used logistic regression analysis to study the association between the FRAMO Index and outcomes in all participants. RESULTS: The participation rate was 83% in this elderly female population (N = 1,248). The 63% of women with 0 to 1 risk factor had a 2-year hip fracture risk of 0.8% and mortality risk of 3.2%. In contrast, women with 2 to 4 risk factors had a 2-year hip fracture risk of 5.4% (odds ratio = 7.5; 95% confidence interval, 3.0-18.4) and mortality risk of 23.7% (odds ratio = 9.5; 95% confidence interval, 6.0-14.9). These differences remained significant after adjustment for age as a continuous variable. Mortality increased with the number of risk factors. The proportion of women reporting previous vertebral fractures was higher among the group specifically questioned about vertebral radiographs (P <.001). CONCLUSIONS: The FRAMO Index identified the majority of women who experienced hip fractures during a 2-year follow-up, who might have been candidates for intensified preventive measures. The FRAMO Index, based on 4 binary risk factors, would be practical for routine use in primary care.
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4.
  • Almqvist, Erik G., et al. (author)
  • Factors influencing insulin sensitivity in patients with mild primary hyperparathyroidism before and after parathyroidectomy
  • 2012
  • In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 72:2, s. 92-99
  • Journal article (peer-reviewed)abstract
    • Objectives. Primary hyperparathyroidism (PHPT) is associated with cardiovascular disease. The aims of this study were to investigate lipid and glucose metabolism in mild PHPT, and to identify whether insulin sensitivity correlates with circulating levels of adiponectin, SHBG, and osteocalcin before and after parathyroidectomy (PTX). Materials and methods. Forty-five patients with PHPT were examined before and 1 year after PTX. Circulating levels of triglycerides, total cholesterol, HDL-cholesterol, insulin, glucose, adiponectin, SHBG, osteocalcin, and erythropoietin were measured. Results. At baseline, the mean serum levels of total cholesterol, LDL-cholesterol and triglycerides were above the upper reference limit or in the upper normal range, and insulin sensitivity was reduced as assessed using the HOMA index. One year after parathyroidectomy, serum lipids as well as HOMA index and erythropoietin were unchanged while adiponectin had increased (p < 0.05), and SHBG and osteocalcin had decreased (p < 0.05 and p < 0.0001, respectively). HOMA index correlated negatively with circulating levels of adiponectin, SHBG and osteocalcin. In multiple regression analysis SHBG was the most important predictor of insulin sensitivity, both pre- and postoperatively. Conclusion. Untreated mild PHPT is associated with a moderate derangement of lipid and glucose metabolism. As previously shown in population-based cohorts, insulin sensitivity is positively associated with circulating concentrations of adiponectin, SHBG and osteocalcin. One year after PTX, the mean level of adiponectin was increased, but the levels of SHBG and osteocalcin had decreased and the levels of serum lipids and the insulin sensitivity remained unchanged as compared with baseline.
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5.
  • Andersson, Niklas, 1970, et al. (author)
  • A variant near the interleukin-6 gene is associated with fat mass in Caucasian men
  • 2010
  • In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 34:6, s. 1011-9
  • Journal article (peer-reviewed)abstract
    • CONTEXT: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.
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6.
  • Andersson, Niklas, 1970, et al. (author)
  • Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men
  • 2009
  • In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 33:5, s. 525-533
  • Journal article (peer-reviewed)abstract
    • Context: Immune functions seem to have connections to variations in body fat mass. Studies of knockout mice indicate that endogenous interleukin (IL)-1 can suppress mature-onset obesity. Objective: To systematically investigate our hypotheses that single- nucleotide polymorphisms (SNPs) and/or haplotypes variants in the IL-1 gene system are associated with fat mass. Subjects: The Gothenburg osteoporosis and obesity determinants (GOOD) study is a population-based cross-sectional study of 18-20 year-old men (n = 1068), from Gothenburg, Sweden. Major findings were confirmed in elderly men (n = 3014) from the Swedish part of the osteoporotic fractures in men (MrOS) multicenter population-based study. Main Outcome Measure: The genotype distributions and their association with body fat mass in different compartments, measured with dual-energy X-ray absorptiometry (DXA). Results: Out of 15 investigated SNPs in the IL-1 receptor antagonist (IL1RN) gene, a recently identified 30 untranslated region C4T (rs4252041, minor allele frequency 4%) SNP was associated with the primary outcome total fat mass (P = 0.003) and regional fat masses, but not with lean body mass or serum IL-1 receptor 1 (IL1RN) levels. This SNP was also associated with body fat when correcting the earlier reported IL1RN_2018 T4C (rs419598) SNP (in linkage disequilibrium with a well-studied variable number tandem repeat of 86 bp). The association between rs4252041 SNP and body fat was confirmed in the older MrOS population (P = 0.03). The rs4252041 SNP was part of three haplotypes consisting of five adjacent SNPs that were identified by a sliding window approach. These haplotypes had a highly significant global association with total body fat (P < 0.001). None of the other investigated members of the IL-1 gene family displayed any SNPs that have not been described previously to be significantly associated with body fat. Conclusions: The IL1RN gene, shown to enhance obesity by suppressing IL-1 effects in experimental animals, have no previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men. International Journal of Obesity (2009) 33, 525-533; doi: 10.1038/ijo.2009.47; published online 17 March 2009
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7.
  • Atroshi, Isam, et al. (author)
  • Low calcaneal bone mineral density and the risk of distal forearm fracture in women and men: a population-based case-control study.
  • 2009
  • In: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 45:4, s. 789-93
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: We used dual X-ray absorptiometry (DXA) to measure calcaneal bone mineral density (BMD) and estimate the prevalence of osteoporosis in a population with distal forearm fracture and a normative cohort. METHODS: Patients 20 to 80 years of age with distal forearm fracture treated at one emergency hospital during two consecutive years were invited to calcaneal BMD measurement; 270 women (81%) and 64 men (73%) participated. A DXA heel scanner estimated BMD (g/cm(2)) and T-scores. Osteoporosis was defined as T-score< or =-2.5 SD. Of the fracture cohort, 254 women aged 40-80 years and 27 men aged 60-80 years were compared with population-based control cohorts comprising 171 women in the age groups 50, 60, 70 and 80 years and 75 men in the age groups 60, 70, and 80 years. RESULTS: In the fracture population no woman below 40 years or man below 60 years of age had osteoporosis. In women aged 40-80 years the prevalence of osteoporosis in the distal forearm fracture cohort was 34% and in the population-based controls was 25%; the age-adjusted prevalence ratio (PR) was 1.32 (95% CI 1.00-1.76). In the subgroup of women aged 60-80 years the age-adjusted prevalence ratio of osteoporosis was 1.28 (95% CI 0.95-1.71). In men aged 60-80 years the prevalence of osteoporosis in the fracture cohort was 44% and in the population-based controls was 8% (PR 6.31, 95% CI 2.78-14.4). The age-adjusted odds ratio for fracture associated with a 1-SD reduction in calcaneal BMD was in women aged 40-80 years 1.4 (95% CI 1.1-1.8), in the subgroup of women aged 60-80 years 1.2 (95% CI 0.95-1.6), and in men aged 60-80 years 2.6 (95% CI 1.7-4.1). Among those aged 60-80 years the area under the ROC curve was in women 0.56 (95% CI 0.49-0.63) and in men 0.80 (95% CI 0.70-0.80). CONCLUSIONS: The age-adjusted prevalence of osteoporosis based on calcaneal BMD is higher in individuals with distal forearm fracture than in population-based controls. BMD impairment is associated with increased odds ratio for forearm fracture in both women and men but the differences between cases and controls are more pronounced in men than in women, which may have implications in fracture prevention.
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10.
  • Ben-Avraham, Dan, et al. (author)
  • The complex genetics of gait speed : Genome-wide meta-analysis approach
  • 2017
  • In: Aging. - : Impact Journals, LLC. - 1945-4589. ; 9:1, s. 209-246
  • Journal article (peer-reviewed)abstract
    • Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.
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