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Sökning: WFRF:(McGuigan Fiona)

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  • Albagha, Omar M E, et al. (författare)
  • Linkage disequilibrium between polymorphisms in the human TNFRSF1B gene and their association with bone mass in perimenopausal women
  • 2002
  • Ingår i: Human Molecular Genetics. - Oxford University Press. - 0964-6906. ; 11:19, s. 95-2289
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis is a multifactorial disease with a strong genetic component characterized by reduced bone density and increased fracture risk. A candidate locus for regulation of hip bone mineral density (BMD) has been identified on chromosome 1p36 by linkage analysis. One of the positional and functional candidate genes located within this region is the tumour necrosis factor receptor superfamily member 1B (TNFRSF1B). In order to investigate whether allelic variation in TNFRSF1B contributes to regulation of bone mass, we studied several polymorphisms of this gene in a population based cohort study of 1240 perimenopausal women from the UK. We studied a T676G change in exon 6 (196: Met-Arg) and three SNPs (G593A, T598G, and T620C) in the 3'UTR of the gene. The 3'UTR SNPs were in strong linkage disequilibrium (LD) with each other (P<0.00001), and the exon 6 SNP was in LD with G593A and T598G (P<0.00001). We found no association between T676G alleles and BMD at the spine or hip. However, haplotype analysis showed that subjects homozygous for the A593-T598-C620 haplotype (n=85) had femoral neck BMD values 5.7% lower than those who did not carry the haplotype (n=1155; P<0.00008) and this remained significant after correcting for confounding factors and multiple testing (P<0.0009). Regression analysis showed that the ATC haplotype accounted for 1.2% of the population variance in hip BMD and was the second strongest predictor after body weight. In summary, our work supports the view that allelic variation in the 3'UTR of TNFRSF1B gene contributes to the genetic regulation of bone mass, with effects that are specific for femoral neck BMD.
  • Bartosch, Patrik S., et al. (författare)
  • Frailty and prediction of recurrent falls over 10 years in a community cohort of 75-year-old women
  • ????
  • Ingår i: Aging clinical and experimental research. - Kurtis. - 1594-0667.
  • 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.
  • Berglundh, Sofia, et al. (författare)
  • C-reactive protein, bone loss, fracture, and mortality in elderly women: a longitudinal study in the OPRA cohort.
  • 2015
  • Ingår i: Osteoporosis International. - Springer. - 1433-2965. ; 26:2, s. 727-735
  • Tidskriftsartikel (refereegranskat)abstract
    • This longitudinal study investigates the association between C-reactive protein (CRP), osteoporosis, fractures, and mortality in 1044 elderly women. CRP was not an indicator for low bone mineral density (BMD), bone loss, or fracture in elderly women; however, women with elevated CRP levels over a prolonged period lost more bone over the 10-year follow-up, although fracture risk was not increased.
  • Buchebner, David, et al. (författare)
  • Association Between Hypovitaminosis D in Elderly Women and Long- and Short-Term Mortality-Results from the Osteoporotic Prospective Risk Assessment Cohort
  • 2016
  • Ingår i: Journal of the American Geriatrics Society. - Wiley-Blackwell. - 0002-8614. ; 64:5, s. 7-990
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the association between low vitamin D levels (<50 nmol/L) and 10-year mortality in women aged 75 and older.DESIGN: Prospective with 15 years of follow-up.SETTING: Malmö, Sweden.PARTICIPANTS: Population-based cohort of 75-year-old women (N = 1,044).MEASUREMENTS: Serum 25-hydroxyvitamin D (25(OH)D) levels at age 75 (n = 1,011), 80 (n = 642), and 85 (n = 348) were categorized as low (<50 nmol/L), intermediate (50-75 nmol/L) and high (>75 nmol/L) at all ages. Hazard ratios (HRs) for all-cause mortality between ages 75 and 90 were calculated according to 25(OH)D category.RESULTS: Between ages 80 and 90, all-cause mortality (HR = 1.8, 95% confidence interval (CI) = 1.3-2.4, P < .001; adjusted for comorbidities (aHR) = 1.9, 95% CI = 1.4-2.6, P < .001) was significantly higher in women with low 25(OH)D levels than in those with high levels. Osteoporosis had the greatest effect on mortality, but even after excluding women with osteoporotic fracture during the risk of dying associated with low 25(OH)D remained greater (HR = 1.8, 95% CI = 1.2-2.7, P = .002; aHR = 1.7, 95% CI = 1.2-2.5, P = .006).CONCLUSION: In this observational study of women aged 75 and older, 25(OH)D levels of less than 50 nmol/L were associated with greater all-cause mortality for up to 10 years. This difference was at least partially independent of comorbidities and fracture, indicating that low 25(OH)D not only is an indicator of impaired health, but also plays a role in disease outcome.
  • Buchebner, David, et al. (författare)
  • Association Between Vitamin D, Frailty, and Progression of Frailty in Community-Dwelling Older Women
  • 2019
  • Ingår i: The Journal of clinical endocrinology and metabolism. - Oxford University Press. - 1945-7197. ; 104:12, s. 6139-6147
  • 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.
  • Buchebner, David, et al. (författare)
  • Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality
  • 2017
  • Ingår i: Endocrine Pathology. - Humana Press. - 2472-1972. ; 1:6, s. 615-624
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear.Objective: To describe normal PTH profiles over time and the association with mortality.Design and Participants: There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years).Main Outcome Measures: PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality.Results: At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082).Conclusions: Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old.
  • Callréus, Mattias, et al. (författare)
  • Adverse Effects of Smoking on Peak Bone Mass May Be Attenuated by Higher Body Mass Index in Young Female Smokers.
  • 2013
  • Ingår i: Calcified Tissue International. - Springer. - 1432-0827. ; 93:6, s. 517-525
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking is associated with postmenopausal bone loss and fracture, but the effect of smoking on bone in younger women is unclear. Peak bone mass is an important determinant for fracture risk; therefore, our aim was to evaluate the association between smoking and bone mass in 25-year-old women, specifically the influence of daily cigarette consumption and total exposure, duration, age at starting smoking, and time since smoking cessation on bone density and fracture risk. Smoking and bone mineral density (BMD) data were available for 1,054 women from the PEAK-25 cohort. Analyses comparing current smokers with women who never smoked were performed using number of cigarettes per day, pack-years, smoking duration, age smoking started, and, for former smokers, age at quitting. BMD did not differ between never, former, and current smokers; and the relative fracture risk in smokers was not significant (relative risk [RR] = 1.2, 95 % confidence interval 0.8-1.9). Among current smokers, BMD decreased with a dose response as cigarette consumption increased (femoral neck p = 0.037). BMD was not significantly lower in young women who had smoked for long duration or started smoking early (p = 0.07-0.64); long duration and early start were associated with higher body mass index (BMI; p = 0.038). Lower BMD persisted up to 24 months after smoking cessation (p = 0.027-0.050), becoming comparable to never-smokers after 24 months. Hip BMD was negatively associated with smoking and dose-dependent on cigarette consumption. Smoking duration was not associated with BMD, although young women with a long smoking history had higher BMI, which might attenuate the adverse effects from smoking.
  • Callréus, Mattias, et al. (författare)
  • Birth weight is more important for peak bone mineral content than for bone density: the PEAK-25 study of 1,061 young adult women.
  • 2013
  • Ingår i: Osteoporosis International. - Springer. - 1433-2965. ; 24:4, s. 1347-1355
  • Tidskriftsartikel (refereegranskat)abstract
    • Lower birth weight has a negative association with adult BMC and body composition in young adult Swedish women. INTRODUCTION: The aim of this study was to evaluate the influence of birth weight on peak bone mass and body composition in a cohort of 25-year-old women. METHODS: One thousand sixty-one women participated in this cross-sectional population-based study using dual energy X-ray absorptiometry (DXA) to assess bone mineral content (BMC), bone mineral density (BMD), and body composition (total body (TB), femoral neck (FN), total hip (TH), lumbar spine L1-L4 (LS), and lean and fat mass). Birth weight data was available for 1,047 women and was categorized into tertiles of low (≤3,180 g), intermediate (3,181-3,620 g), and high (≥3,621 g) birth weight. RESULTS: Significant correlations were observed between birth weight and TB-BMC (r = 0.159, p < 0.001), FN-BMC (r = 0.096, p < 0.001), TH-BMC (r = 0.102, p = 0.001), LS-BMC (r = 0.095, p = 0.002), and lean mass (r = 0.215, p < 0.001). No correlation was observed between birth weight and BMD. The estimated magnitude of effect was equivalent to a 0.3-0.5 SD difference in BMC for every 1 kg difference in birth weight (151 g (TB); 0.22 g (FN); 1.5 g (TH), 2.5 kg TB lean mass). The strongest correlations between birth weight and BMC occurred in women with lowest birth weights, although excluding women who weighed <2,500 g at birth, and the correlation remained significant although slightly weaker. CONCLUSIONS: Women with lower birth weight have lower BMC and less lean and fat mass at the age of 25, independent of current body weight. Lower birth weight has a greater negative influence on bone mass than the positive influence of higher birth weight.
  • Callréus, Mattias, et al. (författare)
  • Country-Specific Young Adult Dual-Energy X-Ray Absorptiometry Reference Data Are Warranted for T-Score Calculations in Women: Data From the Peak-25 Cohort.
  • 2014
  • Ingår i: Journal of Clinical Densitometry. - Elsevier. - 1094-6950. ; 17:1, s. 129-135
  • Tidskriftsartikel (refereegranskat)abstract
    • The aims of this study were to provide normative data for dual-energy X-ray absorptiometry (DXA) in 25-yr-old women and evaluate whether young adult Swedish women have bone mineral density (BMD) comparable with DXA manufacturer reference values and other equivalent populations. BMD at all sites was measured in the population-based Peak-25 cohort (n = 1061 women; age, 25.5 ± 0.2yr). BMD values were standardized (sBMD) and compared against the Third National Health and Nutrition Examination Survey (NHANES III) and other cohorts. Based on the DXA manufacturer-supplied reference values, Z-scores were 0.54 ± 0.98 (femoral neck [FN]), 0.47 ± 0.96 (total hip [TH]), and 0.32 ± 1.03 (lumbar spine [LS]). In comparison with other studies, sBMD was higher in the Peak-25 cohort (FN, 1.5%-8.3%; TH, 3.9%-9.2%; and LS, 2.4%-6.5%) with the exception of trochanter-sBMD which was 2.5% lower compared with NHANES III. The concordance in identifying those in the lowest or highest quartile of BMD was highest between hip measurements (low, 71%-78% and high, 70%-84%), corresponding discordance of 0%-1%. At this age, the correlation between DXA sites was strong (r = 0.62-0.94). BMD in Swedish young adult women is generally higher than has been reported in other equivalently aged European and North American cohorts and suggests that the high fracture incidence in Sweden is not explained by lower peak bone mass. The use of nonregional-specific DXA reference data could contribute to misdiagnosed osteoporosis in elderly women.
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