High bone density due to a mutation in LDL-receptor-related protein 5.
High bone density due to a mutation in LDL-receptor-related protein 5.
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DOI：
10.1056/nejm200209193471216
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发表时间：
2002-09
期刊：
影响因子：
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通讯作者：
L. Hofbauer;B. Maisch;J. Schaefer
中科院分区：
文献类型：
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作者：
L. Hofbauer;B. Maisch;J. Schaefer
作者：Boyden et al. (May 16期）1描述了一个由于低密度脂蛋白（LDL）受体相关蛋白5（LRP 5）基因突变而具有高骨密度的家族。我们的研究小组先前报道了LRP 5突变的发现，该突变导致了一个远亲的高骨量常染色体显性遗传综合征。[2]我们发现另一个具有完全相同突变的家族被发现了，这既令人兴奋又令人瞩目。我们相信，Boyden等人描述的家族与我们家族之间的差异具有科学和临床意义，Boyden等人描述的高骨量表型似乎比我们家族更极端。在我们的亲属中，受影响成员髋关节和脊柱骨矿物质密度的z评分之和范围为4.57 - 12.28，而Boyden等人提供的数据计算的相同评分范围为8.99 - 14.60。与我们的研究相反，Boyden等人报告了骨钙素、转化生长因子b1和纤连蛋白水平的显著升高，其他生物标志物水平在正常范围内。如果骨形成持续，人们会期望其他重塑标志物，特别是再吸收，也会升高，除非骨矿物质密度的增加在整个生命中持续。在我们的研究中，我们发现高骨量和正常骨量的人之间的标记物水平没有显着差异。我们最初没有观察到不寻常的临床特征，例如Boyden等人描述的腭隆凸和方颌。初步随访显示，我们家族中的一名未受影响的成员和两名受影响的成员有小隆凸
To the Editor: Boyden et al.(May 16 issue) 1 describe a kindred with high bone density due to a mutation in the gene for low-density lipoprotein (LDL) receptor–related protein 5 (LRP5). Our group previously reported the finding of a mutation in LRP5 that causes an autosomal dominant syndrome of high bone mass in an extended kindred. 2 We found it both exciting and remarkable that another kindred with exactly the same mutation has been identified. We believe that the differences between the kindred described by Boyden et al. and our kindred are of scientific and clinical interest.The high-bone-mass phenotype described by Boyden et al. appears to be even more extreme than that in our kindred. The sum of the z scores for the bone mineral density of the hip and spine in affected members of our kindred ranged from 4.57 to 12.28, whereas the same scores calculated with the data provided by Boyden et al. ranged from 8.99 to 14.60. In contrast to our study, Boyden et al. report significant elevations in the levels of osteocalcin, transforming growth factor b1, and fibronectin, with the levels of other biologic markers in the normal range. If bone formation were continuing, one would expect other markers of remodeling, particularly resorption, to be elevated as well, unless the increases in bone mineral density continued throughout life. In our study, we found no significant differences in the levels of markers between people with high bone mass and those with normal bone mass. We initially observed no unusual clinical features such as the torus palatinus and square jaw described by Boyden et al. Preliminary follow-up revealed that one unaffected member and two affected members of our kindred had small torus