Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab

TRANSLATIONAL THERAPY IN PATIENTS WITH OSTEOGENESIS IMPERFECTA - A PILOT TRIAL ON TREATMENT WITH THE RANKL-ANTIBODY DENOSUMAB

Pilot study to assess the efficacy of a therapy with the RANKL-antibody denosumab in children 5-10 years of age with mutation in COL1A1 or COL1A2 leading to Osteogenesis imperfecta. Efficacy will be assessed by DXA measurements at the lumbar spine of the areal bone mineral density (BMD) which is the most frequently used parameter in trials investigating osteoporosis.

The hypothesis of the study is:

Osteoclastic activity which is increased in OI could be reduced by inhibition of osteoclast maturation. Denosumab inhibits maturation of the osteoclasts by inhibiting RANKL. BMD could be increased during a 36 week treatment course with denosumab measured after 48 weeks.

Inclusion Criteria

• Male or female subjects between 5 years and 10 years of age with molecular proven Osteogenesis imperfecta (COL1A1/A2 mutation)
• Subjects must have been treated for a minimum of 2 years with bisphosphonates prior to study entry

Exclusion Criteria:

• Hypocalcemia (<1.03 mmol/l ionized Calcium)
• Subjects with reduced renal function (estimated GFR (Schwartz formula) <30ml/min/1.73m2)
• Any other abnormal finding such as physical examination or laboratory evaluation, in the opinion of the investigator that is indicative of a disease that would compromise the safety of the patient when getting denosumab s.c.