Osteogenesis imperfecta (OI) is a monogenic bone fragility disorder that usually is caused by mutations in one of the two genes coding for collagen type I alpha chains, COL1A1 or COL1A2. Mutations in at least 18 other genes can also lead to an OI phenotype. As genetic testing is more widely used, mutations in these genes are also more frequently discovered in individuals who have a propensity for fractures, but who do not have other typical clinical characteristics of OI. Intravenous bisphosphonate therapy is still the most widely used drug treatment approach. Preclinical studies in OI mouse models have shown encouraging effects when the antiresorptive effect of a bisphosphonate was combined with bone anabolic therapy using a sclerostin antibody. Other novel experimental treatment approaches include inhibition of transforming growth factor beta signaling with a neutralizing antibody and the inhibition of myostatin and activin A by a soluble activin receptor 2B. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Keywords: COLLAGEN TYPE I; FRACTURES; MUSCLE; OSTEOBLAST; OSTEOGENESIS IMPERFECTA; SEQUENCING.