Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK.
J Bone Miner Res. 2012 Oct;27(10):2170-8. doi: 10.1002/jbmr.1659.
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.
骨丢失率在整个衰老期通过多种复杂机制而变化。因此，遗传因素对骨丢失的作用也可能类似地发生变化。在这项研究中，我们通过一项大型基于双胞胎的纵向研究调查了年龄对骨丢失遗传成分的影响。在 TwinsUK 和健康老龄化双胞胎研究（HATS）的 17 年随访期间，对 7056 对双胞胎进行了 15491 次髋部和腰椎双能 X 射线吸收法（DXA）扫描。在这些受试者中，2716 名年龄＞35 岁的女性双胞胎至少进行了两次扫描，且两次扫描之间的时间间隔＞4 年（平均随访 9.7 年），这些受试者被纳入本分析。我们使用混合效应随机系数回归模型来预测确切年龄为 40、45、50、55、60、65、70、75 和 80 岁时髋部和脊柱骨密度（BMD）值，调整了基线年龄、体重、身高和激素替代疗法的持续时间。然后，我们估计了这些年龄范围内 BMD 测量值变化的遗传度。不同年龄时，髋部和脊柱 BMD 的横断面遗传度均较高（范围为 69%至 88%）。BMD 变化的遗传度较低且更具变异性，髋部通常为 0%至 40%，脊柱为 0%至 70%；40 至 45 岁之间，遗传因素解释了全髋骨密度丢失的 39.9%（95%置信区间[CI]，25%-53%），股骨颈丢失的 46.4%（95% CI，32%-58%），腰椎丢失的 69.5%（95% CI，59%-77%）。这些估计值随着年龄的增加而降低，并且 65 岁以后似乎没有 BMD 变化的遗传度。脊柱部位存在横断面和纵向 BMD 之间遗传效应共享的一些证据。尽管遗传因素在绝经后早期妇女的骨丢失中具有重要作用，但随着年龄的增长，非遗传机制成为骨丢失的更重要决定因素。
