Bone Abstracts

Osteogenesis imperfecta is a rare disease leading to multiple fractures, skeletal deformities and scoliosis due to a reduced bone mass. Pathological fractures caused by inadequate traumata are the most severe symptom. More than 85% of patients are affected by mutations in COL1A1/A2 impairing quantity and quality of collagen. At present no approved drugs for OI treatment in childhood are available. A single centre prospective pilot study was performed to assess safety and efficacy of an antiresorptive therapy with the RANKL-antibody denosumab in children 5–10 years with OI caused by mutations in COL1A1/A2.

10 children (male n=7, mean age of 7.48 years) with genetically confirmed OI (COL1A1: seven patients) were included. All children were treated at least 2 years with neridronate before trial entry. Denosumab was applicated after a washout phase of at least 6 months every 3 months with 1 mg/kg body weight s.c. for 1 year. Weight adjusted vitamin D and calcium substitution was given 4 weeks after each application. Primary efficacy endpoint was change of areal bone mineral density at the lumbar spine assessed by GE lunar iDXA. Mobility was evaluated by gross motor function measurement (GMFM-88) and 1-min walking test if applicable. Bone metabolism markers were evaluated in serum and urine before and between applications for safety monitoring.

8 out of 10 children completed the trial yet (database closure February 2015). After 40 applications of denosumab no severe side effects were observed. A slight hypocalcemia without clinical relevance was seen in all children within the first days after application.

DXA assessment showed a mean increase of lumbar spine Z-scores of +0.9 SD (n=8) and total body less head Z-scores of +0.6. Mobility improved in all children (mean percent change of: GMFM-88=3.1% (n=8); 1-min walking distance=20.1% (n=6)).

Based on our preliminary results denosumab is effective to reduce bone resorption and increase bone mineral density in children with classical OI. Denosumab seems to be safe in the short-term application at least if a close monitoring/substitution of calcium is guaranteed. Finally, long-term observation and a higher sample size are essential to assess risk–benefit ratio more detailed.

Disclosure: The authors declared no competing interests.