Osteogenesis imperfecta at the beginning of bone and joint decade

Osteogenesis imperfecta (OI), or brittle bone disease, is a heritable disor der characterized by increased bone fragility. Four different types of the disease are commonly distinguished, ranging from a mild condition (type I) to a lethal one (type II). Types [I] and IV are the severe forms surviving the neonatal period. In most cases, there is a reduction in the production of normal type I collagen or the synthesis of abnormal collagen as a result of mutations in the type I collagen genes. These "classic" forms of OI are described in this review. There are instances, however, where alterations in bone matrix components, other than type I collagen, are the basic abnorm alities of the OI. Recently, three such discrete types have been identified by histomorphometric evaluation (types V and VI) and linkage analysis (Rhi zomelic OI). They provide evidence for the as yet poorly understood complex ity of the phenotype-genotype correlation in OI. We also discus bisphosphon ates treatment as well as fracture management and surgical correction of de formities observed in the patients with OI. However, ultimately, strengthen ing bone in OI will involve steps to correct the underlying genetic mutatio ns that are responsible for this disorder. Thus, we also describe different genetic therapeutic approaches that have been tested either on OI cells or on available OI murine models.