Effects of age on genetic influence on bone loss over 17 years in women: the Healthy Ageing Twin Study (HATS).
Effects of age on genetic influence on bone loss over 17 years in women: the Healthy Ageing Twin Study (HATS).
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年龄对 17 岁以上女性骨质流失遗传影响的影响：健康老龄化双胞胎研究 (HATS)。
DOI：
10.1002/jbmr.1659
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Spector,TimothyD
中科院分区：
文献类型：
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作者：
Moayyeri,Alireza;Hammond,ChristopherJ;Hart,DeborahJ;Spector,TimothyD
在整个衰老过程中，骨质流失的速率通过多种复杂的机制发生变化。因此，遗传因素在骨质流失中的作用也可能发生类似的变化。在这项研究中，我们在一项大型的基于双胞胎的纵向研究中调查了年龄对骨质流失遗传成分的影响。在TwinsUK和健康衰老双胞胎研究（HATS）的17年随访中，对7056对双胞胎进行了15491次髋关节和腰椎双能X射线吸收仪（DXA）扫描。在这些受试者中，2716名年龄在50至35岁之间的女性双胞胎被纳入本分析，其中至少两次扫描间隔为11至4年（平均随访9.7年）。我们使用混合效应随机系数回归模型预测精确年龄为40、45、50、55、60、65、70、75和80岁的髋部和脊柱骨密度（BMD）值，调整基线年龄、体重、身高和激素替代治疗持续时间。然后，我们估计了这些年龄范围内骨密度测量变化的遗传性。在不同年龄段，髋部和脊柱横截面骨密度的遗传率估计较高（范围在69%至88%之间）。骨密度变化的遗传率较低，变化较多，髋部一般为0% ~ 40%，脊柱为0% ~ 70%；在40 - 45岁之间，遗传因素解释了全髋关节骨密度损失的39.9%（95%可信区间[CI]， 25%-53%）、股骨颈的46.4% （95% CI, 32%-58%）和腰椎的69.5% （95% CI, 59%-77%）。这些估计值随着年龄的增长而下降，并且在65岁之后，BMD的变化似乎没有遗传性。有证据表明脊柱横截面骨密度和纵向骨密度之间存在共同的遗传效应。尽管遗传因素似乎在早期绝经后妇女的骨质流失中起着重要作用，但随着年龄的增长，非遗传机制成为骨质流失的更重要决定因素。©2012美国骨与矿物研究学会。
The rate of bone loss varies across the aging period via multiple complex mechanisms. Therefore, the role of genetic factors on bone loss may also change similarly. In this study, we investigated the effect of age on the genetic component of bone loss in a large twin‐based longitudinal study. During 17 years of follow‐up in TwinsUK and Healthy Ageing Twin Study (HATS), 15,491 hip and lumbar spine dual‐energy X‐ray absorptiometry (DXA) scans were performed in 7056 twins. Out of these subjects, 2716 female twins aged >35 years with at least two scans separated for >4 years (mean follow‐up 9.7 years) were included in this analysis. We used a mixed‐effects random‐coefficients regression model to predict hip and spine bone mineral density (BMD) values for exact ages of 40, 45, 50, 55, 60, 65, 70, 75, and 80 years, with adjustment for baseline age, weight, height, and duration of hormone replacement therapy. We then estimated heritability of the changes in BMD measures between these age ranges. Heritability estimates for cross‐sectional hip and spine BMD were high (ranging between 69% and 88%) at different ages. Heritability of change of BMD was lower and more variable, generally ranging from 0% to 40% for hip and 0% to 70% for spine; between age 40 and 45 years genetic factors explained 39.9% (95% confidence interval [CI], 25%–53%) of variance of BMD loss for total hip, 46.4% (95% CI, 32%–58%) for femoral neck, and 69.5% (95% CI, 59%–77%) for lumbar spine. These estimates decreased with increasing age, and there appeared to be no heritability of BMD changes after the age of 65 years. There was some evidence at the spine for shared genetic effects between cross‐sectional and longitudinal BMD. Whereas genetic factors appear to have an important role in bone loss in early postmenopausal women, nongenetic mechanisms become more important determinants of bone loss with advanced age. © 2012 American Society for Bone and Mineral Research.