Universität zu Köln

Hoyer-Kuhn, Heike, Netzer, Christian, Koerber, Friederike, Schoenau, Eckhard and Semler, Oliver ORCID: 0000-0003-0029-7556 (2014). Two years' experience with denosumab for children with Osteogenesis imperfecta type VI. Orphanet J. Rare Dis., 9. LONDON: BMC. ISSN 1750-1172

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hoyer-Kuhn, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Netzer, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Koerber, Friederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoenau, Eckhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Semler, Oliver UNSPECIFIED orcid.org/0000-0003-0029-7556 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-428404
DOI:	10.1186/s13023-014-0145-1
Journal or Publication Title:	Orphanet J. Rare Dis.
Volume:	9
Date:	2014
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1750-1172
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GIANT-CELL TUMOR; POSTMENOPAUSAL WOMEN; ANTIBODY DENOSUMAB; MOTOR FUNCTION; BONE TURNOVER; PAMIDRONATE; MARKERS; RANKL Multiple languages Genetics & Heredity; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42840