A new paradigm has emerged for
osteogenesis imperfecta as a
collagen-related disorder. The more prevalent autosomal dominant forms of
osteogenesis imperfecta are caused by primary defects in
type I collagen, whereas autosomal recessive forms are caused by deficiency of
proteins which interact with
type I procollagen for post-translational modification and/or folding. Factors that contribute to the mechanism of dominant
osteogenesis imperfecta include intracellular stress, disruption of interactions between
collagen and noncollagenous
proteins, compromised matrix structure, abnormal cell-cell and cell-matrix interactions and tissue mineralization. Recessive
osteogenesis imperfecta is caused by deficiency of any of the three components of the
collagen prolyl 3-hydroxylation complex. Absence of 3-hydroxylation is associated with increased modification of the
collagen helix, consistent with delayed
collagen folding. Other causes of recessive
osteogenesis imperfecta include deficiency of the
collagen chaperones FKBP10 or
Serpin H1. Murine models are crucial to uncovering the common pathways in dominant and recessive
osteogenesis imperfecta bone dysplasia. Clinical management of
osteogenesis imperfecta is multidisciplinary, encompassing substantial progress in physical rehabilitation and
surgical procedures, management of hearing, dental and pulmonary abnormalities, as well as drugs, such as
bisphosphonates and recombinant
human growth hormone. Novel treatments using
cell therapy or new
drug regimens hold promise for the future.