Osteogenesis imperfecta: pathogenesis, classification, and treatment

Osteogenesis imperfecta (OI) is a congenital skeletal disorder characterized by varying degrees of bone fragility and deformities. Extraskeletal manifestations, such as blue sclera, dentinogenesis imperfecta, growth disturbance, hearing impairment, and muscle weakness, occasionally accompany OI. Many genes have been identified as causative of OI, such as the type I collagen gene and genes involved in the folding, processing, and crosslinking of type I collagen molecules, osteoblast differentiation, and bone mineralization. According to the discovery of the causative gene of OI, nosology and classifications have also been revised and the “dyadic approach” based nomenclature according to the severity and each causative gene of OI was recently adopted. Intravenous or oral bisphosphonates have been administered to treat bone fragility in children with OI and a reduction in the frequency of bone fractures has been reported. However, despite the increase of bone mineral density, evidence of bone fracture prevention is limited. Recently, excessive transforming growth factor β signaling pathway and excessive endoplasmic reticulum stress have been reported as the pathogenesis of OI, and treatment strategies based on these pathogeneses have been developed. This review summarizes the molecular basis, transition of nosology and classification, status of bisphosphonate therapy, and development of treatment strategies.