Osteogenesis imperfecta : current treatment options and future prospects.

Abstract

Osteogenesis imperfecta is a heritable condition characterized by abnormally brittle bones, with an approximate prevalence of 1/20 000 births. Fractures are the main cause of suffering and disability, but owing to the abundance and wide distribution of the defective type I collagen in the body, a variety of symptoms occur. Several types of osteogenesis imperfecta (I-VII) have been described that vary in severity. For many years, therapy consisted of rehabilitation and orthopedic surgery. Presently, pharmacologic therapies aimed at strengthening bone are available, which decrease the pain and fracture rate associated with this condition, and allow more appropriate rehabilitation programs that will hopefully result in a less marked failure to thrive in affected children. In particular, the bisphosphonates, especially pamidronate, have been used for several years. They have been successful in increasing bone mineral density (BMD) and improving bone resistance, leading to a decrease in the fracture rate. Various regimens have been proposed, but it is the therapeutic regimen first used by Glorieux and co-workers in Montreal that has been the most frequently applied.However, as yet there is no definite consensus regarding the indications for therapy, the osteogenesis imperfecta types that are of the greatest concern, the appropriate age at the outset of therapy, and the treatment duration, without yet speaking about the best bisphosphonate regimen for use. The authors have proposed some personal recommendations for the clinical use of bisphosphonates, based on their own experience with the management of patients with this condition; these include the indications for therapy, based on the clinical status, and the treatment duration. These recommendations will certainly not be unanimously endorsed, but they should help to stimulate discussion. Ameliorating BMD is an important step, but will not prevent all fractures because bisphosphonate therapy does not correct the underlying genetic defect. More recently, stem cell replacement therapy in the child or fetus has been proposed as a therapeutic option.All in all, it is possible that, in order to dramatically decrease the fracture rate, combined therapies aimed at both circumventing the consequences of the gene defect using stem cells and reinforcing bone strength with bisphosphonates will have to be considered. Much work is still necessary before recommending these techniques in clinical practice.