Osteogenesis imperfecta: an update on clinical features and therapies.
Osteogenesis imperfecta: an update on clinical features and therapies.
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DOI：
10.1530/eje-20-0299
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发表时间：
2020-10
影响因子：
5.8
通讯作者：
Morello R
中科院分区：
文献类型：
--
作者：
Marom R;Rabenhorst BM;Morello R
成骨不全症（Osteogenesis imperfecta， OI）是一种以骨脆性和骨骼畸形为特征的遗传性骨骼发育不良。虽然大多数病例与编码I型胶原的基因COL1A1和COL1A2的致病变异有关，但高达25%的病例与胶原生物合成途径中起作用或参与成骨细胞分化和骨矿化的其他基因有关。临床上，成骨不全在特征和严重程度上是不同的。除了骨骼方面的发现，它还会影响多个系统，包括牙齿和颅面异常、肌肉无力、听力损失、呼吸和心血管并发症。建议采用多学科的护理方法，不仅要解决骨折，活动能力降低，生长和骨痛，还要解决其他骨骼外的表现。虽然双膦酸盐仍然是成骨不全的主要治疗方法，但人们正在探索新的策略，如硬化蛋白抑制抗体和TGF β抑制，以解决低骨密度和固有的骨脆弱性问题。动物模型研究扩大了对成骨不全的病理机制的理解，并且随着正在进行的临床试验，将允许为这些患者开发更好的治疗方法。
Osteogenesis imperfecta (OI) is an inherited skeletal dysplasia characterized by bone fragility and skeletal deformities. While the majority of cases are associated with pathogenic variants in COL1A1 and COL1A2, the genes encoding type I collagen, up to 25% of cases are associated with other genes that function within the collagen biosynthesis pathway or are involved in osteoblast differentiation and bone mineralization. Clinically, OI is heterogeneous in features and variable in severity. In addition to the skeletal findings, it can affect multiple systems including dental and craniofacial abnormalities, muscle weakness, hearing loss, respiratory and cardiovascular complications. A multi-disciplinary approach to care is recommended to address not only the fractures, reduced mobility, growth and bone pain but also other extra-skeletal manifestations. While bisphosphonates remain the mainstay of treatment in OI, new strategies are being explored, such as sclerostin inhibitory antibodies and TGF beta inhibition, to address not only the low bone mineral density but also the inherent bone fragility. Studies in animal models have expanded the understanding of pathomechanisms of OI and, along with ongoing clinical trials, will allow to develop better therapeutic approaches for these patients.