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Bone Abstracts (2014) 3 PP37 | DOI: 10.1530/boneabs.3.PP37

Bone biomechanics and quality

Bone matrix mineralization after sclerostin antibody treatment in a mouse model of osteogenesis imperfecta

Andreas Roschger1, Paul Roschger1, Michaela Kneissel2 & Frank Rauch3

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1Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital Vienna, Vienna, Austria; 2Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland; 3Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.


Children with osteogenesis imperfecta (OI) still suffer from frequent fractures, despite bisphosphonate treatment. Thus new therapeutic approaches are needed. Sclerostin is a protein that is thought to inhibit bone formation. Treatment with sclerostin antibodies (SclAB) increases bone mass in animal models and in clinical trials and may be a rational therapy for OI as well.

Transgenic (TgOI) Col1a1Jrt/+ mice were generated being a model of OI type IV. 8 weeks old TgOI (n=8) and Wt (n=8) were analyzed after 4 weeks of SclAB treatment and compared to untreated animals (n=7, n=8). The bone mineralization density distribution (BMDD) of the cortical (Ct), metaphyseal spongiosa (MS) and epiphyseal spongiosa (ES) in the distal femur was measured by quantitative backscattered electron imaging. Additionally microCT parameters of the femurs were obtained.

TgOI mice exhibit increased bone matrix mineralization compared to Wt (most frequently occurring Ca concentration: Ct:+6.8% MS:+5.2% ES:+8.2%, P<0.001). The mineralization was also more homogenous in Ct. This fits previous findings in OI models. The percentage of lowly mineralized areas was increased in MS and ES most likely due to the decrease of bone volume (−86.3%, P<0.001).

Treatment with SclAB of Wt and TgOI mice overall led to shifts in the BMDD of the spongiosa towards higher and more homogenously mineralized bone. This is consistent with the observed decrease in percentage of lowly mineralized regions reflecting the increase in bone volume due to SclAB treatment. Two-way ANOVA tests revealed no interaction between genotype and treatment. After treatment, BV/TV of the Wt (+77.7%, P<0.001) and the TgOI (+65.9%, P=0.02) animals were elevated. Wt/SclAB and the TgOI/SclAB mice exhibit more bone volume and a similar increase in matrix mineralization compared to the corresponding untreated animals.

Therefore we conclude, that SclAB treatment has the similar effect on mineralization in TgOI and Wt mice.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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