Ferrari S, Rizzoli R, Slosman D, Bonjour J P
Division of Bone Diseases, University Hospital, Geneva, Switzerland.
J Clin Endocrinol Metab. 1998 Feb;83(2):358-61. doi: 10.1210/jcem.83.2.4583.
Genetic factors are known to explain a major proportion of peak bone mineral mass variance. Whether the influence of these genetic factors is expressed before the pubertal bone mineral mass accrual and whether there is tracking of bone mineral mass during pubertal growth, however, are not clearly established. We prospectively investigated correlations for bone mineral content (BMC), density, and bone size between prepubertal daughters and their premenopausal mothers. Height, weight, lumbar spine (LS), femoral neck (FN) and mid-femoral diaphysis BMC, bone area (BA), areal bone mineral density (aBMD), and volumetric bone mineral apparent density (BMAD) were evaluated in 138 mothers (mean age +/- SD, 40.0 +/- 4.0 yr) and their daughters (8.1 +/- 0.7 yr), who were then remeasured at yearly intervals for 2 yr. Eight-year-old prepubertal daughters had reached 78% and 44% of their mothers' height and weight, respectively. At the various skeletal sites, they had reached 33-43% of their mothers' BMC, 47-69% of their BA, 59-78% of their aBMD, and 75-105% of their BMAD. All body size and bone traits (age-adjusted Z-scores) were significantly correlated between prepubertal daughters and their mothers (r: 0.22-0.36, P < 0.01), except midfemoral diaphysis BMAD. Heritability estimates (1/2 h2), after adjustment for body size and dietary calcium intake, showed that 18-37% of bone traits were directly determined by maternal descent. During the next 2 yr, growth was accompanied by a marked increase of BMC, aBMD, and BA, whereas BMAD changed very little. In contrast, during this period, there were only minor changes in body size or bone trait Z-scores (i.e. < 0.5 Z-scores), which were thus highly correlated between consecutive measurements (r: 0.75-0.92, P < 0.0001). Accordingly, mother-daughter correlations remained unchanged over that period. Although more than 60% of peak bone mineral mass is gained during puberty (mostly at the expense of an increase in bone size while volumetric bone density slightly changes), familial resemblance for most bone traits is already present between daughters and their mothers before puberty. In the girls, moreover, yearly measurements were highly correlated, suggesting tracking of bone traits during pubertal growth. These results indicate that genetic susceptibility to osteoporosis may already be detectable in early childhood.
已知遗传因素可解释骨矿物质峰值方差的很大一部分。然而,这些遗传因素的影响是否在青春期骨矿物质积累之前就已表现出来,以及青春期生长期间骨矿物质是否存在追踪现象,目前尚不清楚。我们前瞻性地研究了青春期前女儿与其绝经前母亲之间骨矿物质含量(BMC)、密度和骨大小的相关性。对138名母亲(平均年龄±标准差,40.0±4.0岁)及其女儿(8.1±0.7岁)的身高、体重、腰椎(LS)、股骨颈(FN)和股骨干中段的BMC、骨面积(BA)、骨面积密度(aBMD)和体积骨矿物质表观密度(BMAD)进行了评估,并在随后的2年中每年进行重新测量。8岁的青春期前女儿的身高和体重分别达到了母亲的78%和44%。在各个骨骼部位,她们的BMC达到了母亲的33 - 43%,BA达到了47 - 69%,aBMD达到了59 - 78%,BMAD达到了75 - 105%。除股骨干中段BMAD外,青春期前女儿与其母亲之间所有身体大小和骨特征(年龄校正Z分数)均显著相关(r:0.22 - 0.36,P < 0.01)。在调整身体大小和膳食钙摄入量后进行的遗传力估计(1/2 h2)表明,18 - 37%的骨特征由母系遗传直接决定。在接下来的2年中,生长伴随着BMC、aBMD和BA的显著增加,而BMAD变化很小。相比之下,在此期间身体大小或骨特征Z分数仅有微小变化(即< 0.5个Z分数),因此连续测量之间高度相关(r:0.75 - 0.92,P < 0.0001)。相应地,母女之间的相关性在此期间保持不变。尽管超过60%的骨矿物质峰值是在青春期获得的(主要是以骨大小增加为代价,而体积骨密度略有变化),但在青春期前,女儿与其母亲之间大多数骨特征的家族相似性就已经存在。此外,在女孩中,每年的测量结果高度相关,表明青春期生长期间骨特征存在追踪现象。这些结果表明,骨质疏松症的遗传易感性在儿童早期可能已经可以检测到。