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Bone Abstracts (2013) 2 OC19 | DOI: 10.1530/boneabs.2.OC19

ICCBH2013 Oral Communications Miscellaneous (6 abstracts)

New therapeutic approach in OI VI: suppression of bone resorption using the RANKL antibody denosumab

Heike Hoyer-Kuhn 1,* , Oliver Semler 1 , Christian Netzer 2 , Jörg Dötsch 1 & Eckhard Schönau 1


1Department of Pediatric and Adolescent Medicine, University of Cologne, Cologne, Germany; 2Institute of Human Genetics, University of Cologne, Cologne, Germany. *Winner of New Investigator Award


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).

Table 1 Changes of calcium and DPD levels during the first treatment cycle.
Calcium (mmol/l) (2.20–2.65)DPD/Crea (nM/mM)
Days after denosumab injectionPat 1Pat 2Pat 3Pat 4Pat 1Pat 2Pat 3Pat 4
Day 12.342.242.212.3570.833.366.941.5
Day 22.222.162.132.2658.928.781.745.2
Day 72.342.102.2423.225.126.319.7
Day 142.271.992.3623.713.426.020.4
Day 292.262.2125.222.725.116.8

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.

Volume 2

6th International Conference on Children's Bone Health

Rotterdam, The Netherlands
22 Jun 2013 - 25 Jun 2013

ICCBH 

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