Abstract Introduction One quarter of osteoporotic fractures occur in men. TBS, a gray-level measurement derived from lumbar spine DXA image texture, is related to microarchitecture and fracture risk ...independently of BMD. Previous studies reported the ability of spine TBS to predict osteoporotic fractures in women. Our aim was to evaluate the ability of TBS to predict clinical osteoporotic fractures in men. Methods 3620 men aged ≥ 50 (mean 67.6 years) at the time of baseline DXA (femoral neck, spine) were identified from a database (Province of Manitoba, Canada). Health service records were assessed for the presence of non-traumatic osteoporotic fracture after BMD testing. Lumbar spine TBS was derived from spine DXA blinded to clinical parameters and outcomes. We used Cox proportional hazard regression to analyze time to first fracture adjusted for clinical risk factors (FRAX without BMD), osteoporosis treatment and BMD (hip or spine). Results Mean followup was 4.5 years. 183 (5.1%) men sustain major osteoporotic fractures (MOF), 91 (2.5%) clinical vertebral fractures (CVF), and 46 (1.3%) hip fractures (HF). Correlation between spine BMD and spine TBS was modest (r = 0.31), less than correlation between spine and hip BMD (r = 0.63). Significantly lower spine TBS were found in fracture versus non-fracture men for MOF (p < 0.001), HF (p < 0.001) and CVF (p = 0.003). Area under the receiver operating characteristic curve (AUC) for incident fracture discrimination with TBS was significantly better than chance (MOF AUC = 0.59, p < 0.001; HF AUC = 0.67, p < 0.001; CVF AUC = 0.57, p = 0.032). TBS predicted MOF and HF (but not CVF) in models adjusted for FRAX without BMD and osteoporosis treatment. TBS remained a predictor of HF (but not MOF) after further adjustment for hip BMD or spine BMD. Conclusion We observed that spine TBS predicted MOF and HF independently of the clinical FRAX score, HF independently of FRAX and BMD in men. Studies with more incident fractures are needed to confirm these findings.
We study an interacting system of N classical particles on a line at thermal equilibrium. The particles are confined by a harmonic trap and repel each other via pairwise interaction potential that ...behaves as a power law ∝∑i≠jN|xi−xj|−k (with k>−2) of their mutual distance. This is a generalization of the well-known cases of the one-component plasma (k=−1), Dyson's log gas (k→0+), and the Calogero-Moser model (k=2). Because of the competition between harmonic confinement and pairwise repulsion, the particles spread over a finite region of space for all k>−2. We compute exactly the average density profile for large N for all k>−2 and show that while it is independent of temperature for sufficiently low temperature, it has a rich and nontrivial dependence on k with distinct behavior for −2<k<1, k>1 and k=1.
Summary
In an observational study population of 62,413 individuals (6,455 10 % with diabetes), diabetes was independently associated with major osteoporotic fractures (MOFs) but did not significantly ...modify the effect of FRAX
TM
risk factors or prior fracture site. However, the presence of diabetes exerted a much stronger effect on hip fracture risk in younger versus older individuals.
Introduction
Diabetes mellitus increases fracture risk independent of risk factors that comprise the WHO FRAX
TM
tool. We explored whether diabetes modifies the effect of FRAX clinical risk factors on MOF and hip fracture risk.
Methods
Using a registry of clinical dual-energy X-ray absorptiometry (DXA) results for Manitoba, Canada, we identified women and men aged 40 years and older undergoing baseline DXA in 1996–2011. Health services data were used to identify diabetes diagnosis, FRAX risk factors and incident fractures using previously validated algorithms. Prior fracture was stratified as clinical vertebral, hip, humerus, forearm, pelvis and ‘other’. Cox proportional hazards models were used to test for statistical interactions of diabetes with FRAX clinical risk factors and prior fracture site.
Results
During a mean follow-up of 6 years, there were 4,218 MOF and 1,108 hip fractures. Diabetes was a significant independent risk factor for MOF adjusted for FRAX risk factors including bone mineral density (BMD) (adjusted hazard ratio aHR 1.32 95 % confidence interval (CI) 1.20–1.46). No significant interactions of FRAX risk factors or prior fracture site with diabetes were identified in analyses of MOF. For predicting hip fractures, age significantly modified the effect of diabetes (aHR age <60, 4.67 95 % CI 2.76–7.89, age 60–69, 2.68 1.77–4.04, age 70–79, 1.57 1.20–2.04, age >80, 1.42 1. 10–1.99;
p
interaction <0.001).
Conclusions
Diabetes is an independent risk factor for MOFs and does not significantly modify the effect of FRAX risk factors or prior fracture site. However, diabetes exerts a much stronger effect on hip fracture risk in younger than older individuals which needs to be considered in hip fracture prediction.
We reconsider the large N asymptotics of Harish-Chandra-Itzykson-Zuber integrals. We provide, using Dyson's Brownian motion and the method of instantons, an alternative, transparent derivation of the ...Matytsin formalism for the unitary case. Our method is easily generalized to the orthogonal and symplectic ensembles. We obtain an explicit solution of Matytsin's equations in the case of Wigner matrices, as well as a general expansion method in the dilute limit, when the spectrum of eigenvalues spreads over very wide regions.
Objectives:
Our objective was to describe changes in glucocorticoid-induced osteoporosis (GIOP) preventive care from 1998–2008 including rates and correlates of bone mineral density (BMD) testing and ...osteoporosis treatment in new long-term glucocorticoid initiations.
Methods:
A population-based study of adults aged 20 yr or older in Manitoba, Canada, was conducted using linked healthcare databases. Subjects with new long-term (≥90 d) systemic glucocorticoid initiations were identified within each fiscal year. High-quality GIOP preventive care was defined by the composite of BMD testing or osteoporosis treatment within 6 months of starting glucocorticoids. For each initiation, we identified sociodemographic and clinical characteristics, prednisone dose equivalents, and prescriber specialty. Multivariable Poisson regression models were used to calculate adjusted incidence rate ratios (aIRR).
Results:
We studied 17,736 new long-term glucocorticoid initiations; one third were at least 10 mg prednisone daily, and most (64%) were prescribed by general practitioners. Overall, 6-month rates of BMD testing were 6%, osteoporosis treatment 22%, and the composite of testing or treatment 25%. From 1998–2008, there were modest increases in BMD testing (from 4 to 6%), osteoporosis treatment (from 15 to 24%), and testing or treatment from 17 to 27%; aIRR = 1.51; 95% confidence interval (CI) = 1.40–1.63. High-quality GIOP preventive care varied significantly by age (16% for those <50 yr vs. 27% for those ≥70 yr; aIRR = 0.57; 95% CI = 0.52–0.63), sex (13% for men vs. 34% for women; aIRR = 0.40; 95% CI = 0.37–0.43), and prescriber (23% general practice vs. 44% rheumatology; aIRR = 0.56; 95% CI = 0.52–0.60).
Conclusions:
Quality of GIOP preventive care has improved but remains suboptimal with only one quarter of those starting long-term glucocorticoids receiving BMD testing or osteoporosis treatment. Interventions to improve GIOP prevention, especially targeting younger patients, men, and nonspecialists, are needed.
Summary
In this large registry-based study, women with diabetes had marginally greater bone mineral density (BMD) loss at the femoral neck but not at other measurement sites, whereas obesity was not ...associated with greater BMD loss. Our data do not support the hypothesis that rapid BMD loss explains the increased fracture risk associated with type 2 diabetes and obesity observed in prior studies.
Introduction
Type 2 diabetes and obesity are associated with higher bone mineral density (BMD) which may be less protective against fracture than previously assumed. Inconsistent data suggest that rapid BMD loss may be a contributing factor.
Methods
We examined the rate of BMD loss in women with diabetes and/or obesity in a population-based BMD registry for Manitoba, Canada. We identified 4960 women aged ≥ 40 years undergoing baseline and follow-up BMD assessments (mean interval 4.3 years) without confounding medication use or large weight fluctuation. We calculated annualized rate of BMD change for the lumbar spine, total hip, and femoral neck in relation to diagnosed diabetes and body mass index (BMI) category.
Results
Baseline age-adjusted BMD was greater in women with diabetes and for increasing BMI category (all
P
< 0.001). In women with diabetes, unadjusted BMD loss was less at the lumbar spine (
P
= 0.017), non-significantly greater at the femoral neck (
P
= 0.085), and similar at the total hip (
P
= 0.488). When adjusted for age and BMI, diabetes was associated with slightly greater femoral neck BMD loss (− 0.0018 g/cm
2
/year,
P
= 0.012) but not at the lumbar spine or total hip. There was a strong linear effect of increasing BMI on attenuated BMI loss at the lumbar spine with negligible effects on hip BMD.
Conclusions
Diabetes was associated with slightly greater BMD loss at the femoral neck but not at other measurement sites. BMD loss at the lumbar spine was reduced in overweight and obese women but BMI did not significantly affect hip BMD loss.
Summary
This is the first study to directly compare the original and recently updated versions of the trabecular bone score (TBS) algorithm. We confirmed improved performance of the new algorithm, ...especially among men.
Introduction
Lumbar spine trabecular bone score (TBS) predicts major osteoporotic fractures (MOFs) and hip fractures (HFs) independent of bone density. The original TBS algorithm (version 1; TBS-v1) was optimized for women of average body size. Limitations were identified when used in men or extremes of body mass index (BMI). The current study evaluates an updated TBS algorithm (version 2; TBS-v2) modified to address these issues.
Methods
From a registry with all DXA results for Manitoba, Canada, we identified 47,736 women and 4348 men age ≥ 40 with baseline spine DXA (GE Prodigy, 1999–2011). Spine TBS was measured using both TBS-v1 and TBS-v2 algorithms. Risk stratification for incident fractures identified from population-based data was assessed from area under the receiver operating characteristic curve (AUROC).
Results
With the TBS-v1 algorithm, average TBS for men was significantly lower than for women (
p
< 0.001) and showed significant inverse correlations with BMI (Pearson
r−
0.40 in men, −0.18 in women both
p
< 0.001). With the TBS-v2 algorithm, average values for men were slightly greater than for women (
p
< 0.001) and there were no significant correlations with BMI (Pearson
r
0.01 in men, −0.01 in women both
p
> 0.1). During mean follow-up of 5 years in men, there were 214 incident MOFs and 47 HFs; during 6 years mean follow-up in women, there were 2895 incident MOFs and 694 HFs. Improvements in fracture prediction were seen with TBS-v2 in both men (change in AUROC for MOFs +0.021
p
= 0.17, HFs +0.046
p
= 0.04) and women (change in AUROC for MOFs +0.012
p
< 0.001, HFs +0.020
p
< 0.001).
Conclusion
The updated TBS algorithm is less affected by BMI, gives higher mean results for men than women consistent with their lower fracture risk, and improves fracture prediction in both men and women.
Using data from genome-wide molecular markers, genomic selection procedures have proved useful for estimating breeding values and phenotypic prediction. The link between an individual genotype and ...phenotype has been modelled using a number of parametric methods to estimate individual breeding value. It has been observed that parametric methods perform satisfactorily only when the system under study has additive genetic architecture. To capture non-additive (dominance and epistasis) effects, nonparametric approaches have also been developed; however, they typically fall short of capturing additive effects. The idea behind this study is to select the most appropriate model from each parametric and nonparametric category and build an integrated model that can incorporate the best features of both models. It was observed from the results of the current study that GBLUP performed admirably under additive architecture, while SVM's performance in non-additive architecture was found to be encouraging. A robust model for genomic prediction has been developed in light of these findings, which can handle both additive and epistatic effects simultaneously by minimizing their error variance. The developed integrated model has been assessed using standard evaluation measures like predictive ability and error variance.
Summary
Although systemic glucocorticoids are commonly used, it is difficult to obtain accurate exposure history. In 50,000 patients, we confirmed that glucocorticoids were associated with reductions ...in bone mineral density (BMD) and increases in fracture and documented that recent and prolonged durations of exposure were particularly associated with adverse events—dose information did not improve risk prediction.
Introduction
Systemic glucocorticoid use, defined as ever having taken supra-physiologic doses for 90-days or more, is a risk factor for low BMD and fractures. This definition does not distinguish recent (vs remote) exposure.
Methods
Within a population-based clinical BMD registry in Manitoba, Canada, we identified all adults over age 40 years tested between 1998 and 2007 and then undertook a cohort study. We identified all oral glucocorticoid dispensations from 1995 to 2009 and stratified exposure by timing (“recent” if within 12 months vs “remote”) and duration (short <90 days vs prolonged ≥90 days). Osteoporosis-related risk factors and treatments and major fractures were obtained using administrative health data.
Results
A total of 12,818 of 52,070 (25 %) subjects had used glucocorticoids prior to BMD testing; the most common exposure was remote short (
n
= 6453) vs recent prolonged (
n
= 2896) vs recent short (
n
= 2644) vs remote prolonged (
n
= 825). Compared to 39,252 never-users, only recent prolonged glucocorticoid use was significantly associated with femoral neck T-score (ANCOVA-adjusted difference −0.13, 95 % CI −0.16 to −0.10,
p
< 0.001). There were 2,842 major (566 hip) fractures over median 5-year follow-up. Compared with never-users, only recent prolonged glucocorticoid use was significantly associated with BMD-independent increases in risk of incident major fracture (5.4 vs 7.7 %, adjusted HR 1.25, 95 % CI 1.07–1.45,
p
= 0.004) and hip fracture (1.1 vs 1.8 %, adjusted HR 1.61, 95 % CI 1.18–2.20,
p
= 0.003).
Conclusions
Recent and prolonged glucocorticoid use (but neither remote nor recent short courses) was independently associated with reduced BMD and increased risk of fractures. These findings should permit clinicians to identify a high-risk group of patients that might benefit from osteoporosis prevention.
Abstract
We predict that cyanoacetylene (HC
3
N) is produced photochemically in the atmosphere of GJ 1132 b in abundances detectable by the James Webb Space Telescope (JWST), assuming that the ...atmosphere is hydrogen dominated and rich in molecular nitrogen (N
2
), methane (CH
4
), and hydrogen cyanide (HCN), as described by Swain et al. First, we construct line lists and cross sections for HC
3
N. Then we apply these cross sections and the model atmosphere of Swain et al. to a radiative transfer model in order to simulate the transmission spectrum of GJ 1132 b as it would be seen by JWST, accounting for the uncertainty in the retrieved abundances. We predict that cyanoacetylene features at various wavelengths, with a clear lone feature at 4.5
μ
m, observable by JWST after one transit. This feature persists within the 1
σ
uncertainty of the retrieved abundances of HCN and CH
4
. The signal is detectable for stratospheric temperatures ≲600 K and moderate stratospheric mixing (10
6
cm
2
s
−1
≲
K
zz
≲ 10
8
cm
2
s
−1
). Our results also indicate that HC
3
N is an important source of opacity that future retrieval models should consider.
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