Osteogenesis Imperfecta: Current Pharmacologic Management and Future Perspectives

Background: Osteogenesis Imperfecta (OI) is a rare hereditary disease characterized by quantitative and qualitative defects in the synthesis of collagen I. Even though new types have been described (XVIII), 85% of the cases can be classified into the traditional types I-IV.

Objectives: To review the literature regarding the current OI management.

Methods: A search in PubMed and Google Scholar databases was performed regarding current strategies and possible future perspectives on the OI management.

Results: Altered bone architecture in OI patients increases bone fragility and therefore leads to fractures. Biphosphonates (BP) are the cornerstone in the OI management. BP increase body mineral density (BMD), cortical thickness and bone mass but their influence in reducing fracture incidence is not established. Anti-RANKL monoclonal antibodies have been introduced mostly in cases resistant to BP, but the quality of reports is poor. Hypercalcemia, hypercalciuria and rebound-effect are common side effects. Results from anti-sclerostin antibodies (Setrusumab), in an open label phase 2a study on adults with OI, have demonstrated an increase in BMD. The use of transforming growth factor β in mouse models has shown anabolic and anti-catabolic effects. Another possible future treatment is fetal multipotent mesechymal cell (MSC) transplantation in severe cases. Two reports are available of prenatal transplantation of MSC with postnatal dosing, leading to an improved clinical course. Fetal MSC transplantation is still experimental and about to be tested in the International multicenter phase I/II clinical trial BOOSTB4.

Conclusion: The OI management has improved. The genomic and proteomic grounds are better understood but issues as to how we can effectively improve the mechanical properties of the bone in order to reduce fracture incidence, still exist. Whether new pharmacologic, genetic or cellular interventions will provide a definitive answer remains to be seen.