Makovey Joanna, Nguyen Tuan V, Naganathan Vasi, Wark John D, Sambrook Philip N
Institute of Bone and Joint Research, Royal North Shore Hospital, University of Sydney, Sydney, Australia.
J Bone Miner Res. 2007 Nov;22(11):1773-80. doi: 10.1359/jbmr.070708.
This longitudinal twin study was designed to assess the heritability of bone loss in peri- and postmenopausal women. A sample of 724 female twins was studied. Baseline and repeat BMD measurements were performed. Results of genetic model-fitting analysis indicated genetic effects on bone loss account for approximately 40% of the between-individual variation in bone loss at the lumbar spine, forearm, and whole body.
BMD and bone loss are important predictors of fracture risk. Although the heritability of peak BMD is well documented, it is not clear whether bone loss is also under genetic regulation. This study was designed to assess the heritability of bone loss in peri- and postmenopausal women.
A sample of 724 female twins (177 monozygotic [MZ] and 185 dizygotic [DZ] pairs), 45-82 yr of age, was studied. Each individual had baseline BMD measurements at the lumbar spine, hip, forearm, and total body by DXA and at least one repeat measure, on average 4.9 yr later. Change in BMD (DeltaBMD) was expressed as percent of gain or loss per year. Intraclass correlation coefficients for DeltaBMD were calculated for MZ and DZ pairs. Genetic model-fitting analysis was conducted to partition the total variance of DeltaBMD into three components: genetic (G), common environment (C), and specific environment, including measurement error (E). The index of heritability was estimated as the ratio of genetic variance over total variance.
The mean annual DeltaBMD was -0.37 +/- 1.43% (SD) per year at the lumbar spine, -0.27 +/- 1.32% at the total hip, -0.77 +/- 1.66% at the total forearm, -0.36 +/- 1.56% at the femoral neck, and -0.16 +/- 0.81% at the whole body. Intraclass correlation coefficients were significantly higher in MZ than in DZ twins for all studied parameters, except at the hip sites. Results of genetic model-fitting analysis indicated that the indices of heritability for DeltaBMD were 0.38, 0.49, and 0.44 for the lumbar spine, total forearm, and whole body, respectively. However, the genetic effect on DeltaBMD at all hip sites was not significant.
These data suggest that, although genetic effects on bone loss with aging are less pronounced than on peak bone mass, they still account for approximately 40% of the between-individual variation in bone loss for the lumbar spine, total forearm, and whole body in peri- and postmenopausal women. These findings are relevant for studies aimed at identification of genes that are involved in the regulation of bone loss.
这项纵向双胞胎研究旨在评估绝经前后女性骨质流失的遗传度。对724名女性双胞胎样本进行了研究。进行了基线和重复骨密度测量。遗传模型拟合分析结果表明，遗传因素对骨质流失的影响约占腰椎、前臂和全身骨质流失个体间差异的40%。
骨密度和骨质流失是骨折风险的重要预测指标。虽然峰值骨密度的遗传度已有充分记录，但骨质流失是否也受遗传调控尚不清楚。本研究旨在评估绝经前后女性骨质流失的遗传度。
研究对象为724名年龄在45 - 82岁的女性双胞胎（177对同卵双胞胎[MZ]和185对异卵双胞胎[DZ]）。每位个体均通过双能X线吸收法（DXA）测量了腰椎、髋部、前臂和全身的基线骨密度，并至少进行了一次重复测量，平均在4.9年后。骨密度变化（DeltaBMD）以每年增减的百分比表示。计算了MZ和DZ双胞胎对DeltaBMD的组内相关系数。进行了遗传模型拟合分析，将DeltaBMD的总方差分为三个部分：遗传因素（G）、共同环境因素（C）和特定环境因素，包括测量误差（E）。遗传度指数估计为遗传方差与总方差之比。
腰椎处的平均年DeltaBMD为-0.37±1.43%（标准差），全髋为-0.27±1.32%，总前臂为-0.77±1.66%，股骨颈为-0.36±1.56%，全身为-0.16±0.81%。除髋部部位外，所有研究参数的MZ双胞胎组内相关系数均显著高于DZ双胞胎。遗传模型拟合分析结果表明，腰椎、总前臂和全身DeltaBMD的遗传度指数分别为0.38、0.49和0.44。然而，所有髋部部位DeltaBMD的遗传效应均不显著。
这些数据表明，尽管衰老对骨质流失的遗传效应不如对峰值骨量的效应明显，但它们仍占绝经前后女性腰椎、总前臂和全身骨质流失个体间差异的约40%。这些发现与旨在鉴定参与骨质流失调控的基因的研究相关。
