Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestr. 59, 22529, Hamburg, Germany.
Institute of Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Calcif Tissue Int. 2018 Jan;102(1):41-52. doi: 10.1007/s00223-017-0332-x. Epub 2017 Oct 10.
The main hallmark of high bone mass (HBM) disorders is increased bone mineral density, potentially visible in conventional radiographs and quantifiable by other radiographic methods. While one of the most common forms of HBM is CLCN7-related autosomal dominant osteopetrosis type II (ADO II), there is no consensus on diagnostic thresholds. We therefore wanted to assess whether CLCN7-osteopetrosis patients differ from benign HBM cases in terms of (1) bone mineral density, (2) bone structure, and (3) microarchitectural abnormalities. 16 patients meeting the criteria of HBM (DXA T/Z-score ≥ 2.5 at all sites) were included in this retrospective study. Osteologic assessment using dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum analyses was performed. The presence of CLCN7 and/or other HBM gene mutations affecting bone mass were tested using a custom designed bone panel. While a DXA threshold for ADO II could be implemented (DXA Z-score ≥ + 6.0), the differences in bone microarchitecture were of lesser extent compared to the benign HBM group. All adult patients with ADO II suffered from elevated fracture rates independent from Z-score. In HR-pQCT, structural alterations, such as bone islets were found only inconsistently. In cases of HBM, a DXA Z-score ≥ 6 may be indicative for an inheritable HBM disorder, such as ADO II. Microarchitectural bone alterations might represent local microfracture repair or accumulation of cartilage remnants due to impaired osteoclast function, but seem not to be correlated with fracture risk.
高骨量（HBM）疾病的主要特征是骨矿物质密度增加，在常规 X 光片上可见，也可以通过其他 X 光方法进行量化。虽然最常见的 HBM 形式之一是 CLCN7 相关常染色体显性遗传性骨硬化症 II 型（ADO II），但目前还没有关于诊断阈值的共识。因此，我们想评估 CLCN7-骨硬化症患者在以下方面是否与良性 HBM 病例不同：（1）骨矿物质密度，（2）骨结构，和（3）微观结构异常。这项回顾性研究纳入了符合 HBM 标准（所有部位的 DXA T/Z 评分≥2.5）的 16 名患者。使用双能 X 射线吸收法（DXA）、高分辨率外周定量计算机断层扫描（HR-pQCT）和血清分析进行骨骼评估。使用定制的骨面板测试是否存在影响骨量的 CLCN7 和/或其他 HBM 基因突变。虽然可以实施 ADO II 的 DXA 阈值（DXA Z 评分≥+6.0），但与良性 HBM 组相比，骨微观结构的差异程度较小。所有患有 ADO II 的成年患者均发生骨折，与 Z 评分无关。在 HR-pQCT 中，仅发现骨岛等结构改变不一致。在 HBM 病例中，DXA Z 评分≥6 可能提示存在遗传性 HBM 疾病，如 ADO II。微观结构骨改变可能代表局部微骨折修复或由于破骨细胞功能受损而软骨残余物的积累，但似乎与骨折风险无关。
