Osteogenesis imperfecta-pathophysiology and therapeutic options.

IF 2.4 Q1 PEDIATRICS
Julia Etich, Lennart Leßmeier, Mirko Rehberg, Helge Sill, Frank Zaucke, Christian Netzer, Oliver Semler
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引用次数: 34

Abstract

Osteogenesis imperfecta (OI) is a rare congenital disease with a wide spectrum of severity characterized by skeletal deformity and increased bone fragility as well as additional, variable extraskeletal symptoms. Here, we present an overview of the genetic heterogeneity and pathophysiological background of OI as well as OI-related bone fragility disorders and highlight current therapeutic options.The most common form of OI is caused by mutations in the two collagen type I genes. Stop mutations usually lead to reduced collagen amount resulting in a mild phenotype, while missense mutations mainly provoke structural alterations in the collagen protein and entail a more severe phenotype. Numerous other causal genes have been identified during the last decade that are involved in collagen biosynthesis, modification and secretion, the differentiation and function of osteoblasts, and the maintenance of bone homeostasis.Management of patients with OI involves medical treatment by bisphosphonates as the most promising therapy to inhibit bone resorption and thereby facilitate bone formation. Surgical treatment ensures pain reduction and healing without an increase of deformities. Timely remobilization and regular strengthening of the muscles by physiotherapy are crucial to improve mobility, prevent muscle wasting and avoid bone resorption caused by immobilization. Identification of the pathomechanism for SERPINF1 mutations led to the development of a tailored mechanism-based therapy using denosumab, and unraveling further pathomechanisms will likely open new avenues for innovative treatment approaches.

Abstract Image

成骨不全:病理生理学和治疗选择。
成骨不全症(OI)是一种罕见的先天性疾病,其严重程度广泛,以骨骼畸形和骨脆性增加以及其他可变的骨骼外症状为特征。在这里,我们概述了成骨不全以及成骨不全相关的骨脆性疾病的遗传异质性和病理生理背景,并强调了当前的治疗选择。最常见的成骨不全是由两种I型胶原基因的突变引起的。停止突变通常导致胶原蛋白数量减少,导致轻度表型,而错义突变主要引起胶原蛋白的结构改变,导致更严重的表型。在过去的十年中,已经发现了许多其他的致病基因,这些基因涉及胶原蛋白的生物合成、修饰和分泌、成骨细胞的分化和功能以及骨稳态的维持。对成骨不全患者的治疗包括使用双膦酸盐作为最有希望的抑制骨吸收从而促进骨形成的治疗方法。手术治疗确保疼痛减轻和愈合,而不会增加畸形。通过物理治疗及时活动和定期加强肌肉是提高活动能力,防止肌肉萎缩和避免固定引起的骨吸收的关键。serinf1突变的病理机制的确定导致了使用denosumab的量身定制的基于机制的治疗的发展,揭示进一步的病理机制可能会为创新的治疗方法开辟新的途径。
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CiteScore
2.20
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