| 1. |
- Zillikens, M. C., et al.
(författare)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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| 2. |
- Medina-Gomez, C., et al.
(författare)
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Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 102:1, s. 88-102
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course. © 2017 American Society of Human Genetics
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| 3. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 4. |
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| 5. |
- Albaik, Mai, et al.
(författare)
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Bone mass in Saudi women aged 20–40 years : the association with obesity and vitamin D deficiency
- 2022
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Summary: This study describes that low bone density is prevalent in premenopausal Saudi women, especially women of normal weight and vitamin D deficiency. Although BMD is higher in obese young women, this may not be beneficial later in life in conjunction with persistent vitamin D deficiency. Introduction: Not attaining peak bone mass is one crucial factor contributing to the risk of developing osteoporosis and suffering fractures in later life. The objectives of this study were to describe the normal range of bone mineral density (BMD) and bone mineral content (BMC) in premenopausal Saudi women in relation to obesity and vitamin D insufficiency. Methods: A cross-sectional study involving 312 healthy Saudi women aged 20–40. All women were clinically examined. BMD (g/cm2) and BMC (g) assessed at total body (TB), femoral neck (FN) and lumbar spine (LS) were performed using dual-energy X-ray absorptiometry (DXA). Obesity was defined as BMI ≥ 30 kg/m2 and vitamin D deficiency defined as 25(OH)D < 50 nmol/L. Results: Almost half of the studied women were obese, and the majority (86.2%) were deficient in vitamin D. Mean BMD in TB 1.060 ± 0.091, FN 0.918 ± 0.153 and LS 1.118 ± 0.123 g/cm2, while TB-BMC 2077 ± 272 g. When classified by BMI, the proportion with low bone density was 2–3 times higher among the normal weight compared to the obese women, p < 0.001. In the cohort overall, ~ 19% of these young premenopausal women had osteopenia or osteoporosis at the femoral neck, but 26% in normal weight, vitamin D deficient women. Conclusion: This study shows low bone density in premenopausal Saudi women, particularly those with normal weight. While obesity appears to confer some protection against vitamin D deficiency at this age, this is assumed to change in later life.
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| 6. |
- Bartosch, Patrik S., et al.
(författare)
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Frailty and prediction of recurrent falls over 10 years in a community cohort of 75-year-old women
- 2020
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Ingår i: Aging clinical and experimental research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 32:11, s. 2241-2250
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Tidskriftsartikel (refereegranskat)abstract
- Background: Frailty captures the age-related declines in health leading to increased vulnerability, including falls which are commonplace in older women. The relationship between frailty and falls is complex, with one leading to the other in a vicious cycle. Aims: This study addresses the gap in understanding how patterns of frailty and falls propensity interact, particularly in those who have not yet entered the falls-frailty cycle. Methods: The Osteoporosis Risk Assessment cohort consists of 1044 community-dwelling women aged 75, with 10 years of follow-up. Investigations were performed and a frailty index constructed at baseline, 5 and 10 years. Falls were self-reported for each previous 12 months. Analysis was two-directional, firstly based on frailty status and second, based on falls status. Recurrent falls was the primary outcome. Results: Baseline frailty was a significant predictor of recurrent falls after 5 and 10 years [(OR 2.55 (1.62–3.99); 3.04 (1.63–5.67)]. Among women who had no history of falls at age 75, frailty was a stronger predictor of falls at 5 years [OR 3.06 (1.59–5.89)] than among women who had previously fallen. Discussion: Frailty is significantly associated with recurrent falls and most pronounced in those who are frail but have not yet fallen. Conclusions: This suggests that frailty should be an integral part of falls-risk assessment to improve identification of those at risk of becoming fallers.
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| 7. |
- Buchebner, David, et al.
(författare)
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Association Between Vitamin D, Frailty, and Progression of Frailty in Community-Dwelling Older Women
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:12, s. 6139-6147
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Vitamin D (25OHD) is involved in many physiological functions that decline with age, contributing to frailty and increased risk for negative health outcomes. Whether 25OHD is a long-term risk marker for frailty over a longer time and whether it is consistent with advancing age is unclear. OBJECTIVE: To investigate the association between 25OHD and frailty in older women followed for 10 years. DESIGN AND SETTING: Prospective, population-based, cohort study in Malmö, Sweden. PARTICIPANTS: Community-dwelling women, age 75 years (N = 1044) with reassessments at ages 80 (n = 715) and 85 (n = 382) years. METHODS: Frailty was quantified using a 10-variable frailty index. Women were categorized as 25OHD insufficient (<50 nmol/L) or sufficient (≥50 nmol/L). RESULTS: At ages 75 and 80 years, women with insufficient 25OHD were frailer than women with sufficient 25OHD (0.23 vs 0.18, P < 0.001; and 0.32 vs 0.25, P = 0.001, respectively). At age 80 years, 25OHD insufficiency was associated with subsequent frailty 5 years later (0.41 vs 0.32; P = 0.011). Accelerated progression of frailty was not associated with lower 25OHD levels, and 25OHD level >75 nmol/L was not additionally beneficial with regard to frailty. No association between 25OHD and frailty was observed at age 85 years. Within the frailty index, variables associated with 25OHD were related to muscle strength and function. CONCLUSION: In this study, 25OHD insufficiency was associated with increased frailty in all but the oldest old. This study supports the value of maintaining sufficient 25OHD levels for healthy aging.
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| 8. |
- Ebrahimi, Parvaneh, et al.
(författare)
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Epigenome-wide cross-tissue correlation of human bone and blood DNA methylation–can blood be used as a surrogate for bone?
- 2021
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 16:1, s. 92-105
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Tidskriftsartikel (refereegranskat)abstract
- Difficulty in obtaining bone tissue is an obstacle to studying epigenetics to understand gene–environment interactions, and their role in disease pathogenesis. Blood is an obvious alternative and in this proof of principle study, our aim was to systematically investigate whether blood is a viable surrogate for bone. We measured epigenome-wide DNA methylation at 850 K CpG sites in matched trabecular bone and peripheral blood collected from the same patients at the same time-point (n = 12 women; 66–85y), to investigate the between-tissue correspondence. What constituted a CpG site with corresponding methylation in both tissues was stringently defined. Only sites highly correlated (r2 > 0.74; FDR q-value <0.05) and at least 80% similarity in methylation level (Δβ <0.2) between paired samples were retained. In total, 28,549 CpG sites were similarly methylated in bone and blood. Between 33% and 49% of loci associated with bone phenotypes through GWAS were represented among these sites, and major pathways relevant to bone regulation were enriched. The results from this study indicate that blood can mirror the bone methylome and capture sites related to bone regulation. This study shows that in principal, peripheral blood is a feasible surrogate for bone tissue in DNA methylation investigations. As the first step, this will provide a platform for future studies in bone epigenetics, and possibly for larger-scale epidemiological studies.
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| 9. |
- Egund, Lisa, et al.
(författare)
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High Luteinizing Hormone and Lower Levels of Sex Hormones in Younger Men With Distal Radius Fracture
- 2020
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Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the sex steroid hormone profile in younger men with distal radius fracture (DRF) to elucidate if this could explain the low bone density and osteoporosis previously observed. In a case–control study, 73 men with DRF (mean age 38 ± 9 years; range, 20–51) was compared with 194 age-matched, population controls. Performed assays: total testosterone (TT), calculated free testosterone (cFT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and total estradiol (E2). BMD hip and spine were measured. Fracture cases had lower cFT (298 versus 329 pmol/L; p = 0.008), but not TT, compared with controls. FSH and SHBG were not statistically different. LH was almost 30% higher (5.7 versus 4.5 IU/L; p < 0.001) and a lower E2 was observed (80.0 versus 87.1; p = 0.098). Men with DRF had a lower E2/SHBG ratio compared with controls (2.3 versus 2.9; p = 0.013). A higher proportion of the fracture group had low TT (<10.5 nmol/L; 21% versus 11%; p = 0.052), low cFT (<220 pmol/L; 18% versus 8%; p = 0.017), and low E2 (<73 pmol/L; 48% versus 35%; p = 0.044). Odds ratio (OR) for fracture when having low cFT was 2.3 (95% CI, 1.02–5.49; p = 0.044); with low E2, the OR was 1.7 (95% CI, 0.96–2.96). In this study in young men with DRF exploring sex hormone levels, we find that sex hormone profiles may be disturbed with a lower E2/SHBG ratio, lower cFT, and higher LH. Estrogen is also a strong determinant of bone mass in men; hence, low levels of E2 may be contributing to the observed lower BMD and these differences may be relevant to fracture risk.
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| 10. |
- Egund, Lisa, et al.
(författare)
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Patient-related outcome, fracture displacement and bone mineral density following distal radius fracture in young and older men
- 2020
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Distal radius fractures can adversely affect wrist function; for men with this fracture, the role played by fracture severity, age and osteoporosis on fracture outcome has not been sufficiently studied. Objective: To describe patient-reported outcome and the association with bone integrity, fracture severity and future fracture risk among young and older men with distal radius fracture. Methods: This prospective study includes 133 men with acute distal radius fracture, mean age 54 (range 21–88), who were followed for 12 months. They were categorized as younger (< 65) and older (65+). Main outcome was DASH (Disability of the Arm, Shoulder and Hand) at 12 months; DASH > 15 was defined as poor outcome. Fractures were classified and radiographic displacement identified at initial presentation and follow-up. BMD was measured and FRAX 10-year probability of fracture calculated. Results: Disability was higher in older men (DASHmedian 10 vs 2; p = 0.002); a clinically meaningful difference (ΔDASH = 10, p = 0.017) remained after adjustment for displacement, fracture classification and treatment method. Almost 50% of older men vs 14% in younger had poor outcome, p < 0.001. Bone mineral density did not independently predict outcome. Older men with a displaced fracture at initial presentation had greater disability (DASHmedian, IQR 45, 14;73) and risk of fracture (FRAXmajor osteoporotic 14, 8;21). Conclusion: Men over the age of 65 with a distal radius fracture are more likely to have post-fracture disability regardless of radiographic appearance. Fracture displacement, indicating impaired bone strength, is also more common and associated with an increased risk of fracture within 10-years. Secondary fracture prevention should therefore be considered in men presenting with distal radius fracture.
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