Bone Abstracts

Background: Osteogenesis imperfecta (OI) as a rare disease is characterized by reduced bone mass, increased fracture rate, bone deformities and skeletal pain.

Currently patients are treated with i.v. bisphosphonates regardless of the underlying mutation.

Recently the gene causing OI type VI was described (SERPINF-1, altered RANKL-pathway). This leads to a new understanding of the underlying pathophysiology and offered a new therapeutic approach.

OI type VI is not caused by a reduced synthesis of collagen in the osteoblasts but by an increased activity of osteoclasts leading to a higher proportion of bone resorption.

Objective: Suppression of bone resorption in children with OI type VI treated with the RANKL antibody denosumab?

Methods: This case serie includes four patients (male=4, median age 10.0 years) with confirmed mutation in SERPINF-1 and reduced response to bisphosphonates (measured by inadequate reductions of urinary deoxypyridinolin (DPD) level as parameter for osteoclastic suppression) who were treated with denosumab 1 mg/kg body weight s.c. every 12 weeks. DPD levels were determined under treatment as a marker of bone resorption. Bone mineral density (BMD (g/cm²)) was determined after a completed 1 year course of treatment by DEXA of the lumbar spine.

Results: Urinary DPD/creatinin dropped to the normal range after each injection (Table 1).

BMD of the lumbar spine increased during the first year of treatment more than during bisphosphonate treatment. Levels of serum calcium were stable under oral substitution (Table 1).

Conclusions: Denosumab was well tolerated and laboratory parameters and BMD measurement provided evidence that this treatment reversibly reduced bone resorption in OI VI. A prospective trial to evaluate efficacy and safety is needed for further proof of the effect of denosumab in patients with OI caused by mutations in COL1A1/COL1A2.