Osteogenesis imperfecta: Current and future treatments

Osteogenesis imperfecta (OI) is a heritable disease of bone due to mutations involving type I collagen synthesis. Current concerns in both children and adults involve the effectiveness of intravenous and orally administered bisphosphonates, which are generally considered the standard of care. However, questions remain in terms of fracture prevention rates in children and adults, as well as questions related to dosing schedules and the duration of bisphosphonate treatment. This paper reviews collagen synthesis in OI as related to potential treatment strategies. Potential pharmacological treatments for OI involve: RANK ligand inhibitors, cathepsin K and sclerostin inhibitors. Teriparatide is currently in clinical trials. Molecular strategies include the use of hammerhead ribozymes and siRNA methodology to silence the mutant COL1 allele. Fetal intrauterine mesenchymal cell transplantation has shown promising results despite limited trials. In the situation of quantitative collagen defects, genetic treatment would involve the addition of a COL1 functional allele into the mesenchymal stem cells of a patient. In dominant/negative COL1 mutations the strategy would be to silence the mutant allele (gene targeting). Stem cell therapy involving induced pleuripotent stem cells as a means of repopulating the marrow with functional osteoblasts producing normal type I collagen may offer great therapeutic potential.