Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Guangdong Mental Health Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
J Bone Miner Res. 2021 Nov;36(11):2184-2192. doi: 10.1002/jbmr.4406. Epub 2021 Jul 8.
Observational studies have suggested that sleep and circadian disturbances are potentially modifiable risk factors for low bone mineral density (BMD), but the causal relationship is unclear. This study aimed to (i) replicate the findings by examining observational association of sleep traits with low estimated BMD); (ii) examine whether these associations were causal by using Mendelian randomization (MR) analyses; and (iii) investigate potential modulation effects of sex and menopause. A total of 398,137 White British subjects (aged 39 to 73 years) with valid BMD estimated by quantitative ultrasound of the heel (eBMD) at baseline were included. Linear regression analyses and inverse-variance weighted method were used as main methods for observational and one-sample MR analyses, respectively, to investigate the associations between self-reported sleep traits (sleep duration, chronotype, daytime sleepiness, and insomnia) and low eBMD. Furthermore, sensitivity analyses were performed in subgroups based on sex and menopause in both observational and MR analyses. In observational analyses, short/long sleep, insomnia, and definite eveningness were associated with low eBMD (short sleep: β = -0.045, effect in standard deviation change of rank-based inverse normally transformed eBMD; long sleep: β = -0.028; sometimes insomnia: β = -0.012; usually insomnia: β = -0.021; definite eveningness: β = -0.047), whereas definite morningness was associated with decreased risk of low eBMD (β = 0.011). Subgroup analyses suggested associations of short/long sleep and definite eveningness with low eBMD among men, short sleep with low eBMD among premenopausal women, and short sleep, eveningness, and daytime sleepiness among postmenopausal women. In bidirectional MR analyses, there was no causal relationship between sleep traits and eBMD in either overall sample or subgroup analyses. In summary, although observational analysis showed a robust association of low eBMD with sleep duration, chronotype, and insomnia, there was no evidence of causal relationship as suggested by MR analysis. © 2021 American Society for Bone and Mineral Research (ASBMR).
观察性研究表明，睡眠和昼夜节律紊乱可能是骨密度（BMD）降低的可改变风险因素，但因果关系尚不清楚。本研究旨在：(i) 通过检查睡眠特征与低估计 BMD 的观察性关联来复制发现；(ii) 通过孟德尔随机化（MR）分析来检验这些关联是否存在因果关系；(iii) 研究性别和绝经的潜在调节作用。共纳入了 398137 名白种英国人（年龄 39 至 73 岁），他们在基线时通过足跟定量超声（eBMD）获得了有效的 BMD 估计值。线性回归分析和倒数方差加权法分别作为观察性和单样本 MR 分析的主要方法，用于研究自我报告的睡眠特征（睡眠时间、昼夜类型、白天嗜睡和失眠）与低 eBMD 之间的关联。此外，在观察性和 MR 分析中，均在性别和绝经亚组中进行了敏感性分析。在观察性分析中，短/长睡眠时间、失眠和明确的傍晚型与低 eBMD 相关（短睡眠时间：β=-0.045，在基于等级逆正态变换 eBMD 的标准偏差变化中的效应；长睡眠时间：β=-0.028；偶尔失眠：β=-0.012；经常失眠：β=-0.021；明确傍晚型：β=-0.047），而明确的早晨型与低 eBMD 的风险降低相关（β=0.011）。亚组分析表明，短/长睡眠时间和明确的傍晚型与男性的低 eBMD 相关，短睡眠时间与绝经前女性的低 eBMD 相关，以及短睡眠时间、傍晚型和白天嗜睡与绝经后女性的低 eBMD 相关。在双向 MR 分析中，在总体样本或亚组分析中，睡眠特征与 eBMD 之间均无因果关系。总之，尽管观察性分析显示低 eBMD 与睡眠时间、昼夜类型和失眠之间存在牢固的关联，但 MR 分析并未提示因果关系。
