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Federal government websites often end in. The site casual relationship enderby secure. Previous observational studies on the casual relationship enderby between sleep casual relationship enderby and fracture have yielded contradictory results. The goal of this casual relationship enderby was to replicate the findings in a large longitudinal cohort and then conduct a Mendelian randomization MR analysis to infer the causality between sleep behaviors and casual relationship enderby risk.
We further inferred the causal relationship between self-reported sleep behaviors and hip fracture using the MR approach. However, no causal relationship was observed for other sleep traits. In conclusion, our findings suggest that short sleep duration has a potential detrimental effect on hip fracture.
Improving sleep patterns is of significance for developing hip fracture preventive strategies in the middle-aged and the elderly populations. Fracture is a major health risk for the elderly population due to its high mortality and high risk of disability [ 12 ].
Inthe estimated number of new osteoporotic fractures worldwide was 9. China is experiencing rapid population aging and facing great challenges from an increasing number of hip fractures [ 5 ]. As a result, identifying risk factors for hip fracture is critical for developing comprehensive preventive strategies and lowering the societal cost burden.
Hip fractures in the elderly result from multiple etiological factors, such as falls, physical activity, poor bone health, cognitive impairment, and lifestyle factors [ 678 casual relationship enderby. Extensive studies have shown that reduced bone mineral density BMD is the key determinant of the risk of hip fractures.
Falls are another direct cause of hip fractures in the elderly. Some other modifiable lifestyle factors, such as external body padding, also offer great promise in the prevention of hip fracture [ 9 ]. Disruptions in the physiology of sleep and circadian rhythmicity may have an effect in bone health and increase the risk of fracture [ 101112 ]. From experimental studies, mice lacking molecular casual relationship enderby genes e. Similarly, the expression of clock genes in human bone has endogenous circadian rhythmicity [ 17 ].
Sleep disturbance has also been linked to incidental fractures in epidemiologic studies. Interestingly, individuals with sleep disorders are more likely to consume caffeine or medications e. Other sleep behaviors, such as sleep duration, daytime napping, chronotype, sleep quality, insomnia, and snoring, have also been linked to bone mineral density BMD and fracture risk [ 11212223 ]. Even though some pathophysiological research has suggested that genetics, brain structure, cytokines, hormones, and increased food intake may play a role in the link between sleep disorder and hip fracture, the underlying mechanism is not fully understood [ 2425casual relationship enderby27 ].
Observational studies have suggested associations between sleep behaviors and fracture risk, but the findings have been inconsistent. Conversely, the Study of Osteoporotic Fractures SOF found that long sleep duration was associated with an increased risk of non-spine fractures in older postmenopausal women [ 29 ].
Several studies recently suggested a U-shaped relationship between sleep duration and fracture risk [ 3031 ]. Surprisingly, the role of sleep traits on bone health varies by fracture site and gender [ 3233 ]. For example, poorer sleep, such as shorter sleep duration, sleepiness, and snoring, were associated with vertebral fracture but not hip fracture in another longitudinal cohort study [ 33 ].
Such controversial findings may be in part due to differences casual relationship enderby the populations studied. In addition, it is also important to consider some other unmeasured variables for example, outdoor activity, morbidities, and depressionas well as the joint effects of sleep traits. Of note, such epidemiologic associations are vulnerable to reverse causation biases because fracture can influence sleep duration and quality. As a result, current observational studies have a limited ability to further disentangle the potential causal relationship between casual relationship enderby characteristics and fracture.
Mendelian randomization MR investigates causal effects of exposure sleep behaviors and outcome fracture using genetic variants as instrumental variables [ 34 ]. Because the genetic alleles are randomly casual relationship enderby, this method is less susceptible to unmeasured confounding [ 35 ]. Recent reports have identified several genetic variants that are robustly associated with sleep traits e. The public availability of genetic data allows us to investigate causal relationships between sleep traits and fracture in MR studies.
Previous observational studies have discovered that sleep habits influence the casual relationship enderby of fracture. However, it is unclear whether there is casual relationship enderby nonlinear relationship between sleep duration and fracture. The frequency of daytime naps increases with age; is there an association between this and hip fracture, particularly in the elderly?
Furthermore, what are the causal roles of self-reported daytime napping, chronotype, and other sleep phenotypes in fracture? With this in mind, we carried out an observational study to examine the effects of nighttime sleep casual relationship enderby, midday napping, and sleep quality on hip casual relationship enderby within a large Chinese middle-aged and older cohort.
Furthermore, we used genetic variants that are associated with sleep traits sleep duration, chronotype, daytime napping, and insomnia and fracture to infer their possible causal relationships in casual relationship enderby systematic MR study. This is an on-going, nation-wide representative longitudinal health survey of residents aged over 45 years and older casual relationship enderby villages or communities in districts of 28 participating provinces, with follow-up every two years.
The baseline survey of wave 1 included a total of 17, participants, and wave 3 included 20, participants. After consolidating the baseline files, 11, participants remained. Besides, 14 subjects were excluded due to lack of follow-up in The subjects that reported hip fracture at baseline and the subjects missing sleep duration and midday napping information in the baseline survey casual relationship enderby excluded from the longitudinal analysis.
Finally, a total of 10, adults were included in the following analysis Figure 1. This study was performed in line with the principles of the Declaration of Helsinki. All subjects enrolled signed informed consent.
Information on sleep duration and daytime nap duration was recorded using a self-reported questionnaire. BMI was calculated as weight in kilograms divided by height in meters squared. The sleep-related phenotypes used in this study were sleep duration, daytime napping, chronotype, casual relationship enderby insomnia. To establish a causal effect of sleep-related traits on hip fracture, the MR method needs to satisfy the following three assumptions: i the genetic variant Instrumental variable is robustly associated with hip fracture Exposure ; ii the genetic variant does not share common causes potential confounding factors with hip fracture Outcome ; and iii the genetic variant affects hip fracture Outcome exclusively through its effect on sleep-related traits Exposure.
Five main methods are used to estimate causal effects: the random effects inverse-variance weighted IVW method was utilized in the main MR analyses. And MR-Egger regression, the weighted median, simple casual relationship enderby, and weighted mode were performed as complementary analyses. The different methods can provide valid evidence under different conditions.
We utilized the IVW method as the primary analysis for its efficiency to estimate the causal effect. The weighted median was used as an auxiliary method when the heterogeneity was significant, and the MR-Egger regression method was casual relationship enderby to assess the pleiotropy by intercept test. Several sensitivity analyses casual relationship enderby used to check and correct for the causal estimates.
Heterogeneity between SNPs included in each analysis was first tested using the Cochran Q test, and if heterogeneity existed, then random effects IVW was used. A combined sensitivity analysis casual relationship enderby then performed to verify the robustness of our results. A leave-one-out analysis was performed to evaluate the stability of these genetic variants on sleep-related traits.
Logistic regression was applied to analyze the association of sleep duration and midday napping with hip fracture. Potential covariates included in the multivariable adjusted model were age, gender, smoke, drink status, BMI, hypertension, dyslipidemia, diabetes, or high blood sugar. For the joint analysis, a total of 30 categories were defined by combining six categories of sleep duration casual relationship enderby five categories of nap duration.
Then, a logistic regression was carried out on each of the 30 categories and the outcome to obtain the relationship with the outcome. We assessed potential nonlinear trends of incident hip fracture risk by restricted cubic spline regression. Statistical analyses were conducted using Casual relationship enderby 9.
Table 1 shows the demographic characteristics of participants by nighttime sleep and midday napping duration. A total of 10, participants who were in the inception cohort in were included in this study.
Among them, 8. The average length of nighttime sleep duration and midday napping time were 6. During 4 years of follow-up, a total of incidental hip fracture cases were observed. After adjusting for covariates, the results remain consistent Table 2. Restricted cubic spline regression analysis was further used to model the association between nighttime sleep duration and hip fracture. Remarks: Values in bold in the casual relationship enderby are meaningful results; ref: indicates the reference group.
Furthermore, we examined the association of midday napping with hip fracture risk. This suggested that baseline midday napping time had no effect on the risk casual relationship enderby hip fracture.
Besides, upon conducting a stratified analysis using selected covariates e. Furthermore, we assessed the joint effect of nighttime sleep duration and midday napping time on fracture risk. Forest plot of logistic regression analysis of sleep duration and risk of hip fracture, stratified by baseline information. Forest plot of logistic regression analysis of midday napping and risk of hip fracture stratified by baseline information.
However, there is no statistical association between difficulty falling asleep or waking casual relationship enderby and hip fracture. Among four sleep phenotypic studies we conducted e. The scatter plot and funnel plot are shown in Supplementary Figures S1 and S2.
In addition, we removed three SNPs with casual relationship enderby allele frequency palindromes. As a result, estimates for 26 SNPs were included in the analysis of sleep duration and hip fracture.
Casual relationship enderby, the leave-one-out sensitivity analysis confirmed the stability casual relationship enderby the causal inference Supplementary Figure S3. However, we failed to observe a causal casual relationship enderby of daytime napping, chronotype, and insomnia with fracture.
Casual relationship enderby plot of Mendelian randomization for the relationship between sleep duration and casual relationship enderby fracture risk.
MR-Egger regression, the weighted median, simple casual relationship enderby, and weighted mode were performed as complementary analyses.
In this study, we replicated previous observational findings by examining the association of self-reported sleep duration, midday napping, and sleep quality with hip fracture in a large Chinese middle-aged and elderly cohort [ 3043 ]. Our results suggested that participants who self-reported short sleep duration and poor sleep quality casual relationship enderby. Moreover, a U-shaped relationship was observed between sleep duration and fracture risk.
Furthermore, we found a joint effect of sleep duration and midday napping on the risk of hip fracture. In the two-sample MR analysis, the results suggested that genetically determined self-reported sleep duration was potentially negatively associated with the risk of hip fracture.
However, no evidence of a causal relationship between casual relationship enderby sleep traits, such as chronotype, daytime napping, and insomnia, and fracture was found in the MR analysis.
Of the sleep characteristics, previous observational studies investigated the association of self-reported sleep duration with fracture but reported conflicting results.