scholarly journals Observational and genetic evidence highlight the association of human sleep behaviors with the incidence of fracture

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yu Qian ◽  
Jiangwei Xia ◽  
Ke-Qi Liu ◽  
Lin Xu ◽  
Shu-Yang Xie ◽  
...  

AbstractWe combined conventional evidence from longitudinal data in UK Biobank and genetic evidence from Mendelian randomization (MR) approach to infer the causality between sleep behaviors and fracture risk. We found that participants with insomnia showed 6.4% higher risk of fracture (hazard ratio [HR] = 1.064, 95% CI = 1.038–1.090, P = 7.84 × 10−7), falls and bone mineral density (BMD) mediated 24.6% and 10.6% of the intermediary effect; the MR analyses provided the consistent evidence. A U-shape relationship was observed between sleep duration and fracture risk (P < 0.001) with the lowest risk at sleeping 7–8 h per day. The excessive daytime sleepiness and “evening” chronotype were associated with fracture risk in observational study, but the association between chronotype and fracture did not show in MR analyses. We further generated a sleep risk score (SRS) with potential risk factors (i.e., insomnia, sleep duration, chronotype, and daytime sleepiness). We found that the risk of fracture increased with an increasing SRS (HR = 1.087, 95% CI = 1.065–1.111, P = 1.27 × 10−14). Moreover, 17.4% of the fracture cases would be removed if all participants exhibited a healthy sleep pattern. In conclusion, insomnia had a causal effect on fracture, falls had a larger intermediary effect than BMD in this association. Individuals with fracture risk could benefit from the intervention on unhealthy sleep pattern.

2021 ◽  
Author(s):  
Yu Qian ◽  
Xia Jiangwei ◽  
Ke-Qi Liu ◽  
Lin Xu ◽  
Shu-Yang Xie ◽  
...  

Abstract Here, we combined conventional evidence from longitudinal data in UK Biobank and genetic evidence from Mendelian randomization (MR) approach to infer the causality between sleep behaviors and fracture risk. We found that participants with insomnia showed a 7.0% higher risk of fracture (hazard ratio [HR] = 1.070, 95%CI = 1.045–1.096, P = 1.87×10− 8), falls and BMD mediated 26% and 10% of the intermediary effect, the MR analyses provided the consistent evidence. A U-shape relationship was observed between sleep duration and fracture risk (P < 0.001) with the lowest fracture risk at sleeping 7–8 hours per day. The excessive daytime sleepiness and “evening” chronotype were associated with fracture risk in observational study, but the association between chronotype and fracture did not show in MR analyses. We further generated a sleep risk score (SRS) with potential risk factors (i.e., insomnia, sleep duration, chronotype, and daytime sleepiness). We found that the risk of fracture increased with an increasing SRS (HR = 1.095, 95%CI = 1.073–1.118, P < 2×10− 16). Moreover, 19.4% of the fracture cases would be removed if participants exhibited a healthy sleep pattern. In conclusion, insomnia had a causal effect on fracture, falls had a larger intermediary effect than BMD in this association. Individuals with fracture risk could benefit from the intervention on unhealthy sleep pattern.


2021 ◽  
Author(s):  
Todd L Bredbenner

Increased risk of skeletal fractures due to bone mass loss is a major public health problem resulting in significant morbidity and mortality, particularly in the case of hip fractures. Current clinical methods based on two-dimensional measures of bone mineral density (areal BMD or aBMD) are often unable to identify individuals at risk of fracture. The underlying hypothesis of this study was that combinations of femur structural traits are different for those femurs that suffer a fragility fracture within the proximal region of the femur and those that sustain a fracture in either the subtrochanteric or midshaft region of the femur, resulting in an "atypical femur fracture". Accordingly, the objective of this study was to determine the effects of varying combinations of structural traits, material properties, and loading conditions on femur stress response and the location of stress response variation using a validated parametric finite element model. Statistical shape and trait modeling of the femur was used to describe variability in the structural organization of a set of femurs in an efficient manner and the resulting description of structural variability was exploited to investigate how different mechanisms of fracture might occur, whether in the proximal region or in the subtrochanteric and midshaft region. In combination with parameters describing loading condition and material property variation, variation in structural organization is associated with regional increases in maximum principal stress and the percentage of bone expected to damage, and these increases are likely associated with increased fracture risk. The results of this study indicate that there are multiple pathways and combinations of descriptor variation that may result in increased fracture risk and that these pathways can lead to fracture in any region of the femur under both overload conditions, such as with sideways fall loading, and stance loading, which due to the repetitive nature may lead to the accumulation of fatigue damage within the bone and further impair bone condition and increased susceptibility to fracture.


Author(s):  
Johan Quester ◽  
Maria Nethander ◽  
Anna Eriksson ◽  
Claes Ohlsson

Abstract Context A recent pooled analysis of four clinical trials demonstrated that treatment with dehydroepiandrosterone (DHEA) increases lumbar spine BMD (LS-BMD) in women. The causal effect of endogenous adrenal-derived DHEA-sulphate (DHEAS) on LS-BMD and fracture risk in women is unknown. Objective To determine whether circulating DHEAS is causally associated with LS-BMD and fracture risk in women. Methods A two-sample mendelian randomization study using genetic predictors of serum DHEAS derived from the largest available female-specific genome wide association study (GWAS) meta-analysis (n=8 565). Genetic associations with DXA-derived BMD (n=22 900) were obtained from female specific GWAS summary statistics available from the GEFOS consortium while individual-level data of 238 565 women of white ancestry from the UK Biobank were used for associations with fractures (11 564 forearm fractures, 2 604 hip fractures) and estimated heel BMD by ultrasound (eBMD). Results A 1 standard deviation (SD) genetically instrumented increase in log serum DHEAS levels was associated with a 0.21 SD increase in LS-BMD (P-value: 0.01) and a 0.08 SD increase in eBMD (P-value: &lt;0.001). Genetically predicted DHEAS decreased forearm fracture risk (odds ratio (OR): 0.70, 95% confidence interval (CI): 0.55-0.88 per SD increase in DHEAS) while no significant causal association with hip fractures was observed. Conclusions Genetically predicted serum DHEAS increases LS-BMD and decreases forearm fracture risk in women. Based on the results of the present study and previous RCTs of DHEA treatment, we propose that both endogenous adrenal-derived DHEA(S) and pharmacological DHEA treatment improve bone health in women.


2018 ◽  
Vol 50 (03) ◽  
pp. 242-249 ◽  
Author(s):  
Lu Zhang ◽  
Xiaomei Liu ◽  
Hongwei Li

AbstractThe aim of the study was to assess and define the association between parathyroidectomy (PTX) and long-term skeletal outcomes in primary hyperparathyroidism (PHPT) patients. PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were systematically searched up to June 31, 2017, without language restriction. Any study comparing skeletal outcomes [fracture risk or bone mineral density (BMD)] of PHPT patients after more than 12 months of PTX treatment versus non-PTX treatment was included. Pooled relative risks or odds ratios with 95% confidence intervals and weighted mean difference were calculated using random-effects models irrespective of statistical heterogeneity assessed by I2 statistic. Finally, 5 randomized controlled trials (RCTs, n=584) and 10 cohort studies (CSs, n=12202) were included. CSs suggest PTX treatment versus non-PTX treatment is significantly associated with 36% reduction in the risk of fracture, with no heterogeneity, and an increase in the lumbar spine change by 0.55 WMD, with no heterogeneity. RCTs indicate PTX treatment versus non-PTX treatment is significantly associated with BMD change of 0.97 WMD at the lumbar spine with substantial heterogeneity, and 1.23 WMD at the femoral neck with no heterogeneity. The existing CSs indicate PTX-treatment versus non-PTX-treatment might reduce the risk of fracture in PHPT patients. The existing RCTs do not provide sufficient or precise evidence that PTX-treatment affects the fracture risk of PHPT patients, but offer data that subsets of patients who could potentially benefit from PTX-treatment can be identified.


2003 ◽  
Vol 9 (1) ◽  
pp. 10-16 ◽  
Author(s):  
Rosemary A Hannon ◽  
Richard Eastell

Low bone mineral density is a strong risk factor for fractures in the older woman. Biochemical markers of bone turnover may predict fracture risk independently of bone mineral density. High levels of bone resorption markers are associated with increased risk of fracture in both retrospective and prospective studies, although the evidence for bone formation markers and fracture risk is equivocal. For example, the risk of fracture is increased up to two-fold in women with elevated levels of several markers of bone resorption. Prediction models have been developed to predict the 10–year risk of fracture using bone mineral density and biochemical markers of bone turnover and these could prove very useful in clinical practice.


2020 ◽  
Author(s):  
Marina Xavier Carpena ◽  
Carolina Bonilla ◽  
Thais Martins ◽  
Julia P Genro ◽  
Luis Augusto Rohde ◽  
...  

Abstract Study Objectives: To evaluate the level of shared genetic components between attention-deficit/hyperactivity disorder (ADHD) and sleep phenotype, common pathways between them and a possible causal relationship between traits. Methods: We used summary statistics of the largest genome-wide association studies available for ADHD and sleep-related phenotypes including insomnia, napping, daytime dozing, snoring, ease getting up, daytime sleepiness, sleep duration and chronotype. We estimated the genomic correlation between ADHD and sleep-related traits using cross-trait LD-score regression and investigated potential common mechanisms using gene-based cross-trait metanalyses and functional enrichment analyses. The causal effect between the sleep related traits and ADHD was estimated with two sample Mendelian randomization (TSMR), using the Inverse Variance Weighted method as the main estimator. Results: Positive genomic correlation between insomnia, daytime napping, daytime dozing, snoring, daytime sleepiness, short and long sleep duration, and ADHD were observed. Insomnia, sleep duration, daytime sleepiness, and snoring shared genes with ADHD, which were involved in neurobiological functions and regulatory signaling pathways. The TSMR approach supported a causal effect of insomnia, daytime napping, and short sleep duration on ADHD, and of ADHD on long sleep duration and chronotype. Conclusion: Our findings suggest that the comorbidity between sleep phenotypes and ADHD may be mediated by common genetic factors with an important role on neuronal signaling pathways. In addition, it may also exist a causal effect of sleep disturbances and short sleep duration on ADHD, reinforcing the role of these sleep phenotypes as predictors or early markers of ADHD.


2013 ◽  
Author(s):  
Julie Pasco ◽  
Stephen Lane ◽  
Sharon Brennan ◽  
Elizabeth Timney ◽  
Gosia Bucki-Smith ◽  
...  

2020 ◽  
Vol 103 (11) ◽  
pp. 1131-1137

Background: When compared to people without type 2 diabetes mellitus (T2DM), people with T2DM have an increase in fracture risk despite having higher bone mineral density (BMD). Many studies in Caucasians demonstrated that trabecular bone score (TBS) is lower in people with T2DM than those without. The utility of TBS as a fracture risk assessment tool in Asians with T2DM is currently unclear. Objective: To compared lumbar spine (LS) BMD and TBS in Thais with or without T2DM and investigate the correlation between TBS and hemoglobin A1c (HbA1c) and diabetes duration in participants with T2DM. Materials and Methods: The present study was a cross-sectional study that included 97 participants with T2DM (37 men and 60 women) and 342 participants without T2DM (174 men and 168 women). LS-BMD and TBS were obtained. Results: Men and women with T2DM were older and had higher body mass index (BMI). Men with T2DM had significant higher LS-BMD (1.051±0.166 versus 0.972±0.125, p=0.009) and non-significant lower TBS (1.333±0.084 versus 1.365±0.096, p=0.055) than those without. Similarly, women with T2DM had significant higher LS-BMD (0.995±0.155 versus 0.949±0.124, p=0.021) and lower TBS (1.292±0.105 versus 1.382±0.096, p<0.001). After adjusting for age and BMI, T2DM predicted higher BMD in men (p<0.001), but not in women (p=0.143). T2DM was not associated with TBS after adjusting for age and BMI in both genders (p=0.403 and p=0.151 in men and women, respectively). TBS did not correlate with HbA1c in both genders. However, TBS was non-significantly associated with diabetes duration in women (p=0.073), but not in men (p=0.639). Conclusion: T2DM significantly predicted higher LS-BMD only in men and was not independently associated with TBS in both genders. These data highlighted that, in T2DM, there was some variation in the clinical usefulness of BMD and TBS in predicting osteoporotic fractures with regard to clinical characteristic of participants. Keywords: Bone mineral density, Type 2 diabetes mellitus, Trabecular bone score


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