Laboratory of Endocrinology and Metabolism, Department of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Department of Endocrinology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Curr Drug Targets. 2018;19(6):621-635. doi: 10.2174/1389450119666180122161503.
High bone mass (HBM) disorders are a group of clinically and genetically heterogeneous bone diseases characterized by increased bone density on radiographs, due to progressive bone overgrowth or impaired bone resorption, or both. Some HBM cases are secondary to other diseases, such as chronic hepatitis C virus infection. Despite the great advance in gene diagnostic technology, the majority of HBM individuals remain undiagnosed.
In this review, we will summarize the clinical, radiological and biochemical characteristics of HBM cases due to varying etiologies, since these features are helpful in the differential diagnosis of HBM.
Each subgroup of HBM cases shows distinctive clinical, radiological and biochemical characteristics. HBM, due to bone overgrowth, was designated as sclerosteosis, as a result of mutations located in genes critically involved in the Wnt/beta-catenin signal pathway. Mutations in genes encoding factors relevant to the differentiation and maturation of osteoclasts, or critical for the acidification and resorption of osteoclasts may lead to osteopetrosis. Hepatitis C associated osteosclerosis is characterized by a generalized increase in bone mass and markedly elevated serum levels of bone specific alkaline phosphatase.
The clarification of the etiologies of HBM may have a breakthrough role in understanding the molecular mechanisms involved in bone metabolism and may provide new pathways for the intervention of osteoporosis.
高骨量（HBM）疾病是一组临床和遗传上具有异质性的骨骼疾病，其特征为 X 光片上骨密度增加，这是由于进行性骨过度生长或骨吸收受损，或两者兼有。一些 HBM 病例是继发于其他疾病，如慢性丙型肝炎病毒感染。尽管基因诊断技术取得了巨大进步，但大多数 HBM 患者仍未得到诊断。
在这篇综述中，我们将总结不同病因所致 HBM 病例的临床、影像学和生化特征，因为这些特征有助于 HBM 的鉴别诊断。
HBM 的每个亚组都表现出独特的临床、影像学和生化特征。由于位于 Wnt/β-连环蛋白信号通路中关键基因的突变导致的骨过度生长，HBM 被指定为硬化性骨发育不全症。编码与破骨细胞分化和成熟相关的因子的基因突变，或对破骨细胞酸化和吸收至关重要的基因突变，可能导致骨质增生症。丙型肝炎相关性骨硬化症的特征是骨量普遍增加，骨特异性碱性磷酸酶血清水平显著升高。
阐明 HBM 的病因可能对理解骨代谢涉及的分子机制具有突破性作用，并为骨质疏松症的干预提供新途径。
