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Molecular and Cellular Pediatrics
Published in: Molecular and Cellular Pediatrics 1/2020

Open Access 01-12-2020 | Bisphosphonate | Mini review

Osteogenesis imperfecta—pathophysiology and therapeutic options

Authors: Julia Etich, Lennart Leßmeier, Mirko Rehberg, Helge Sill, Frank Zaucke, Christian Netzer, Oliver Semler

Published in: Molecular and Cellular Pediatrics | Issue 1/2020

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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.
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Metadata
Title
Osteogenesis imperfecta—pathophysiology and therapeutic options
Authors
Julia Etich
Lennart Leßmeier
Mirko Rehberg
Helge Sill
Frank Zaucke
Christian Netzer
Oliver Semler
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
Molecular and Cellular Pediatrics / Issue 1/2020
Electronic ISSN: 2194-7791
DOI
https://doi.org/10.1186/s40348-020-00101-9

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