Two years’ experience with denosumab for children with Osteogenesis imperfecta type VI

Orphanet Journal of Rare Diseases

Oliver Semler²  Eckhard Schoenau²  Friederike Koerber¹  Christian Netzer³  Heike Hoyer-Kuhn² 

[1] Institute for Radiology, University of Cologne, Cologne, Germany;Children¿s Hospital, University of Cologne, Kerpenerstr. 62, Cologne, D-50931, Germany;Institute of Human Genetics, University of Cologne, Cologne, Germany

关键词: Bone mineral density;    Denosumab;    RANKL Antibody;    SERPINF1;    Osteogenesis imperfecta VI;   

Others  :  1149697
DOI  :  10.1186/s13023-014-0145-1

 received in 2014-06-12, accepted in 2014-09-08,  发布年份 2014

【 摘 要 】

Background

Osteogenesis imperfecta (OI) is a hereditary disease causing reduced bone mass, increased fracture rate, long bone deformities and vertebral compressions. Additional non skeletal findings are caused by impaired collagen function and include hyperlaxity of joints and blue sclera. Most OI cases are caused by dominant mutations in COL1A1/2 affecting bone formation. During the last years, recessive forms of OI have been identified, mostly affecting posttranslational modification of collagen. In 2011, mutations in SERPINF1 were identified as the molecular cause of OI type VI, and thereby a novel pathophysiology of the disease was elucidated. The subgroup of patients with OI type VI are affected by an increased bone resorption, leading to the same symptoms as observed in patients with an impaired bone formation. Severely affected children are currently treated with intravenous bisphosphonates regardless of the underlying mutation and pathophysiology. Patients with OI type VI are known to have a poor response to such a bisphosphonate treatment.

Method

Deciphering the genetic cause of OI type VI in our 4 patients (three children and one adolescent) led to an immediate translational approach in the form of a treatment with the monoclonal RANKL antibody Denosumab (1 mg/kg body weight every 12 weeks).

Results

Short-term biochemical response to this treatment was reported previously. We now present the results after 2 years of treatment and demonstrate a long term benefit as well as an increase of bone mineral density, a normalization of vertebral shape, an increase of mobility, and a reduced fracture rate.

Conclusion

This report presents the first two-year data of denosumab treatment in patients with Osteogenesis imperfecta type VI and in Osteogenesis imperfecta in general as an effective and apparently safe treatment option.

【 授权许可】

   
2014 Hoyer-Kuhn et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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