de Vernejoul Marie-Christine
INSERM U606 and University Paris 7, Rheumatology Department, Hospital Lariboisière, Assistance Publique Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris, France.
Best Pract Res Clin Rheumatol. 2008 Mar;22(1):71-83. doi: 10.1016/j.berh.2007.12.011.
Sclerosing bone disorders are a diagnostic challenge. However, hereditary sclerosing disorders often have characteristic radiological features that allow their diagnosis. Osteocondensation can result from decreased bone resorption; malignant recessive osteopetroses have been related to mutations in several genes necessary for osteoclast function and also, more recently, to osteoclast differentiation (RANK-L). Albers-Schonberg disease or autosomal-dominant osteopetrosis type II has the characteristic 'sandwich vertebrae' and 'bone within bone' radiological features. It has been related to mutation in chloride channel 7, which is necessary for osteoclast acidification. Osteocondensation can also be related to increased bone formation. Camurati-Engelman dysplasia is a disabilitating disorder with leg pain and weakness, and thickening of the diaphysis of long bones on x ray. It is due to activating mutations in the gene encoding TGF-beta, a growth factor that increases bone formation. Other less common recessive or dominant sclerosing disorders, such as endosteal hyperostosis, sclerostosis, van Buchen disease and high bone mass syndrome, are due to mutations in two genes (LRP5 and SOST) of the Wnt pathway that induce increased osteoblast activity. Recent elucidation of the molecular mechanism responsible for several hereditary diseases with osteocondensation has improved our comprehension of bone remodelling. It has allowed the discovery of new targets for the treatment of postmenopausal osteoporosis, some of which are already being investigated in clinical trials. Molecular mechanism for some hereditary osteocondensation remains to be discovered.
骨硬化性疾病的诊断颇具挑战。然而，遗传性骨硬化性疾病通常具有特征性的放射学表现，有助于其诊断。骨密度增加可由骨吸收减少所致；恶性隐性骨硬化症与破骨细胞功能所需的多个基因突变有关，最近还与破骨细胞分化（核因子κB受体活化因子配体）有关。阿尔伯斯-尚伯格病或常染色体显性II型骨硬化症具有特征性的“夹心椎骨”和“骨中骨”放射学表现。它与氯离子通道7的突变有关，氯离子通道7是破骨细胞酸化所必需的。骨密度增加也可能与骨形成增加有关。卡穆拉蒂-恩格尔曼病是一种致残性疾病，表现为腿痛、乏力，X线显示长骨干骺端增厚。这是由于编码转化生长因子β的基因发生激活突变，转化生长因子β是一种增加骨形成的生长因子。其他不太常见的隐性或显性骨硬化性疾病，如骨内膜增生症、骨硬化症、范布肯病和高骨量综合征，是由于Wnt信号通路中的两个基因（低密度脂蛋白受体相关蛋白5和硬化蛋白）发生突变，导致成骨细胞活性增加。最近对几种导致骨密度增加的遗传性疾病的分子机制的阐明，增进了我们对骨重塑的理解。这使得发现了绝经后骨质疏松症治疗的新靶点，其中一些靶点已在临床试验中进行研究。一些遗传性骨密度增加的分子机制仍有待发现。
