| 1. |
- Cawthon, Peggy M, et al.
(författare)
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What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without? A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium.
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 76:10, s. e321-e327
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Tidskriftsartikel (refereegranskat)abstract
- Cut-points to define slow walking speed have largely been derived from expert opinion.Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not.Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants.Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.
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| 2. |
- Eriksson, Joel, et al.
(författare)
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Limited Clinical Utility of a Genetic Risk Score for the Prediction of Fracture Risk in Elderly Subjects
- 2015
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 30:1, s. 184-194
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Tidskriftsartikel (refereegranskat)abstract
- It is important to identify the patients at highest risk of fractures. A recent large-scale meta-analysis identified 63 autosomal single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD), of which 16 were also associated with fracture risk. Based on these findings, two genetic risk scores (GRS63 and GRS16) were developed. Our aim was to determine the clinical usefulness of these GRSs for the prediction of BMD, BMD change, and fracture risk in elderly subjects. We studied two male (Osteoporotic Fractures in Men Study [MrOS] US, MrOS Sweden) and one female (Study of Osteoporotic Fractures [SOF]) large prospective cohorts of older subjects, looking at BMD, BMD change, and radiographically and/or medically confirmed incident fractures (8067 subjects, 2185 incident nonvertebral or vertebral fractures). GRS63 was associated with BMD (3% of the variation explained) but not with BMD change. Both GRS63 and GRS16 were associated with fractures. After BMD adjustment, the effect sizes for these associations were substantially reduced. Similar results were found using an unweighted GRS63 and an unweighted GRS16 compared with those found using the corresponding weighted risk scores. Only minor improvements in C-statistics (AUC) for fractures were found when the GRSs were added to a base model (age, weight, and height), and no significant improvements in C-statistics were found when they were added to a model further adjusted for BMD. Net reclassification improvements with the addition of the GRSs to a base model were modest and substantially attenuated in BMD-adjusted models. GRS63 is associated with BMD, but not BMD change, suggesting that the genetic determinants of BMD differ from those of BMD change. When BMD is known, the clinical utility of the two GRSs for fracture prediction is limited in elderly subjects. (c) 2014 American Society for Bone and Mineral Research.
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| 3. |
- Harvey, Nicholas C., et al.
(författare)
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Measures of Physical Performance and Muscle Strength as Predictors of Fracture Risk Independent of FRAX, Falls, and aBMD : A Meta-Analysis Of The Osteoporotic Fractures In Men (MrOS) Study
- 2018
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 33:12, s. 2150-2157
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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/height(2)), 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/height(2) (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/height(2) 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/height(2) 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/height(2) was substantially reduced by inclusion of aBMD requires further study, these findings support the consideration of physical performance in fracture risk assessment.
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| 4. |
- Marriott, Ross J, et al.
(författare)
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Factors Associated With Circulating Sex Hormones in Men : Individual Participant Data Meta-analyses.
- 2023
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Ingår i: Annals of internal medicine. - 1539-3704. ; 176:9, s. 1221-1234
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Forskningsöversikt (refereegranskat)abstract
- Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements.To clarify factors associated with variations in sex hormone concentrations.Systematic literature searches (to July 2019).Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry.Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted.Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years.Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data.Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer.Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).
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| 5. |
- 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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