New perspectives on osteogenesis imperfecta
- 14 June 2011
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Endocrinology
- Vol. 7 (9), 540-557
- https://doi.org/10.1038/nrendo.2011.81
Abstract
Osteogenesis imperfecta, or 'brittle bone disease', is a clinically heterogeneous heritable connective tissue disorder, the causative defects of which are directly related to type I collagen. Human cases and murine models of osteogenesis imperfecta are providing insight into common pathways in dominant and recessive osteogenesis imperfecta, leading to the re-evaluation of its definition, classification and therapeutic approaches. A new paradigm has emerged for osteogenesis imperfecta as a collagen-related disorder. The more prevalent autosomal dominant forms of osteogenesis imperfecta are caused by primary defects in type I collagen, whereas autosomal recessive forms are caused by deficiency of proteins which interact with type I procollagen for post-translational modification and/or folding. Factors that contribute to the mechanism of dominant osteogenesis imperfecta include intracellular stress, disruption of interactions between collagen and noncollagenous proteins, compromised matrix structure, abnormal cell–cell and cell–matrix interactions and tissue mineralization. Recessive osteogenesis imperfecta is caused by deficiency of any of the three components of the collagen prolyl 3-hydroxylation complex. Absence of 3-hydroxylation is associated with increased modification of the collagen helix, consistent with delayed collagen folding. Other causes of recessive osteogenesis imperfecta include deficiency of the collagen chaperones FKBP10 or Serpin H1. Murine models are crucial to uncovering the common pathways in dominant and recessive osteogenesis imperfecta bone dysplasia. Clinical management of osteogenesis imperfecta is multidisciplinary, encompassing substantial progress in physical rehabilitation and surgical procedures, management of hearing, dental and pulmonary abnormalities, as well as drugs, such as bisphosphonates and recombinant human growth hormone. Novel treatments using cell therapy or new drug regimens hold promise for the future.Keywords
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