Abstract
Introduction: Osteogenesis imperfecta (OI) is a heritable disease characterized by bone fragility. A wide range of clinical severity and heterogeneity of the molecular defects is reported. Mutations in 14 genes have so far been identified as responsible for OI with either dominant or recessive transmission. OI forms are mainly caused by defects in collagen type I amount, synthesis, structure, post-translation modifications, intracellular trafficking or extracellular processing or in osteoblasts maturation. No definitive cure is available for OI, but the recent discovery of new causative genes have contributed to increased understanding of bone biology allowing the identification of novel therapeutic targets.
Areas covered: This paper reviews classical dominant OI caused by mutation in the genes coding the α chains of type I collagen, as well as the pathophysiology of the more recently discovered, mainly recessive, OI forms. Current surgical and pharmacological treatments as well as novel therapeutic approaches are addressed. A literature search was performed on PubMed, and the most relevant references are cited.
Expert opinion: A critical view on current and novel therapies is given, with particular emphasis on those that target bone cell activity and differentiation, genetic correction of mutant alleles and cellular therapy.
Acknowledgment
Work supported by Fondazione Cariplo grant #2013-0612, Telethon grant #GGP13098 and from the European Community’s Seventh Framework Programme under grant agreement #602300 (SYBIL).
Declaration of interest
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Notes
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