Bone mineral density in sclerosteosis;: Affected individuals and gene carriers
Bone mineral density in sclerosteosis;: Affected individuals and gene carriers
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DOI：
10.1210/jc.2005-1235
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发表时间：
2005-12-01
影响因子：
5.8
通讯作者：
Papapoulos, SE
中科院分区：
文献类型：
--
作者：
Gardner, JC;van Bezooijen, RL;Papapoulos, SE
背景资料：硬化症是一种常染色体隐性遗传的硬化性骨疾病，由于缺乏硬化素，一种由骨细胞分泌的抑制骨形成的蛋白质。在本研究中，我们评估的影响变量表达的遗传缺陷对骨密度（BMD）的患者和载体的决定基因。方法：我们研究了25个人（7例患者和18个表型正常杂合子）。采用双能X线骨密度仪测量腰椎、全髋关节和前臂远端的BMD，并拍摄颅骨侧位X线片。结果如下：患有硬化性骨质疏松症的个体在所有骨骼部位的BMD均显著增加（Z评分范围：腰椎，+ 7.73至+ 14.43;全髋，+ 7.84至+ 11.51;前臂，+ 4.44至+ 9.53）。在杂合子中，BMD在所有骨骼部位均高于年龄匹配的健康个体的平均值，并且具有广泛的正常和明显增加的值。颅骨X线片显示典型的骨质增生的变化，在受影响的个人和轻度或无变化的杂合子。结论：杂合子携带者的骨质疏松症的骨密度值始终高于平均值的健康受试者没有任何骨并发症中遇到的纯合子。这一发现表明，sclerostin的产生和/或活性可以在体内滴定，导致骨量的可变增加，而没有任何不必要的骨骼效应，这一假设对于骨质疏松症新疗法的开发具有明显的意义。
Background: Sclerosteosis is an autosomal recessive sclerosing bone disorder due to deficiency of sclerostin, a protein secreted by the osteocytes that inhibits bone formation. In the present study we assessed the effect of variable expression of the genetic defect on bone mineral density (BMD) in patients and carriers of the determinant gene.Methods: We studied 25 individuals (seven patients and 18 phenotypically normal heterozygotes). BMD was measured by dual x-ray absorptiometry at the lumbar spine, total hip, and distal forearm, and lateral radiographs of the skull were obtained. Results: Individuals with sclerosteosis had markedly increased BMD at all skeletal sites (Z-score ranges: lumbar spine, + 7.73 to + 14.43; total hip, + 7.84 to + 11.51; forearm, + 4.44 to + 9.53). In heterozygotes, BMD was above the mean value of healthy age-matched individuals at all skeletal sites and had a wide range of normal and clearly increased values. Skull radiographs showed the typical hyperostotic changes in affected individuals and mild or no changes in heterozygotes.Conclusions: Heterozygous carriers of sclerosteosis have BMD values consistently higher than the mean of healthy subjects without any of the bone complications encountered in homozygotes. This finding suggests that the production and/or activity of sclerostin can be titrated in vivo, leading to variable increases in bone mass without any unwanted skeletal effects, a hypothesis of obvious significance for the development of new therapeutics for osteoporosis.