Treatment of osteogenesis imperfecta: who, why, what?

Osteogenesis imperfecta (OI) is a heritable disorder characterized by bone fragility and reduced bone mass. It may present with a wide range of severity. About 85% of the cases are linked to mutations in one of the two genes encoding type I collagen. In other cases of OI, there are mutations in the expression of a cartilage-related protein or of 3-prolyl-hydroxylase. Increased bone turnover rate, due to the repair activity triggered to replace weak tissue, is the rule. Often, disuse bone loss further compounds the decrease in bone mass. These findings justify the use of bisphosphonates to reduce osteoclast-mediated bone resorption, and so tilt the remodeling balance towards an increase in bone mass.

Cyclical intravenous pamidronate administration reduces bone pain, and increases bone mass and density. No negative effects on growth or fracture repair have been observed. There is an increase in size of vertebral bodies and thickening of cortical bone, which translates into decreased fracture incidence and improved ambulation. However, the long-term consequences of low bone turnover in children with OI are unknown at the present time. Innovative surgery and specific occupational and physiotherapy programs are integral parts of the treatment protocol. This approach will prevail until gene-based therapies become clinically applicable.