Management of Endocrine Disease: Osteogenesis imperfecta: an update on clinical features and therapies

Abstract

<jats:p>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.</jats:p>

Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

“…Osteogenesis imperfecta is a generalized connective tissue disorder with a wide spectrum of mutations and phenotype manifestations. No definitive therapy currently exists for this disease [ 11 ] and the comprehension of cellular and biochemical mechanisms that determine OI molecular aberrances is crucial in the attempt to improve its clinical management and innovative and more effective therapies development. En route for this ambitious goal, we attempted to ameliorate the understanding of OI affected molecular pathways and of their possible influence on the outcome of the disorder by identifying protein differences occurring among lethal OI type II and non-lethal OI type III patients, which carry glycine substitution at different positions along the α chains of collagen type I.…”

Hospital admissions of patients with osteogenesis imperfecta in the English NHS

“…The management of OI is mainly supportive and focuses on treating the symptoms of the disease. Nevertheless, new treatment strategies are currently under study, including denosumab, teriparatide, sclerostin antibodies, and TGFβ inhibitory antibodies [ 29 ]. Novel therapies may improve the treatment of OI and reduce the need for and duration of hospital admissions.…”

Current Overview of Osteogenesis Imperfecta

“…With an increase in the discovery of the number of gene mutations responsible for causing OI, the classification of OI subtypes has expanded up to OI type XX to date [ 13 , 14 , 15 ]. However, even within the same genetic mutations, various phenotypes are observed; therefore, it is difficult to correlate the molecular genetic classification with the Sillence classification [ 1 ].…”