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Review
. 2019 Feb 20;3(8):e10174.
doi: 10.1002/jbm4.10174. eCollection 2019 Aug.

Osteogenesis Imperfecta: New Perspectives From Clinical and Translational Research

Josephine T Tauer  1 , Marie-Eve Robinson  1 , Frank Rauch  1
Affiliations
Review

Osteogenesis Imperfecta: New Perspectives From Clinical and Translational Research

Josephine T Tauer et al. JBMR Plus. .

Abstract

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.

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Figures

Figure 1
Figure 1
Lower extremity radiographs. (A) A 21‐month‐old boy with osteogenesis imperfecta (OI) type I caused by a frameshift mutation in COL1A1. (B) A 3‐year‐old girl with OI type III caused by a glycine substitution in COL1A2. Note the severe bowing of both femurs and tibias, and healing fracture of the distal right femur. (C) A 3‐year‐old boy with OI type IV caused by a valine deletion in COL1A2. Note the deformities of both femurs and tibias, and healing fracture of the left fibula. (D) A 19‐month‐old boy with OI type V caused by a IFITM5 mutation. Note the hyperplastic callus formation of the left femoral shaft and radiodense metaphyseal bands adjacent to the growth plate.
Figure 2
Figure 2
Lateral view of a diaphyseal femur fracture in a 21‐month‐old boy with osteogenesis imperfecta type IV, without previous deformities of the femur and in the absence of prior bisphosphonates treatment.
Figure 3
Figure 3
Lateral spine radiograph of a girl with osteogenesis imperfecta type IV showing reshaping of vertebral bodies during bisphosphonate treatment. (A) Age 2 years. (B) Age 15 years.
See this image and copyright information in PMC

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