Bone Abstracts

Introduction: Osteogenesis imperfecta (OI) is characterized by low bone mass, skeletal fragility and, frequently, short stature. We previously showed in oim/oim mice that sclerostin inhibition increased bone mass, mineral content and strength. Here, we compared the body length and the sizes of long bones, head and vertebrae between oim/oim and wildtype mice and analyzed the effect of sclerostin antibody (Scl-Ab) on these parameters.

Materials and methods: Five-week-old oim/oim and wild-type mice received s.c. injections of either Scl-Ab VI (25 mg/kg) or vehicle (PBS) twice a week for 10 weeks. Body length and bone growth were evaluated on DXA scans collected at 5 and 15 weeks of age by measuring the snout-sacrum length. After termination at 15 weeks, the length of humerus and tibia and the craniofacial dimensions of the head were measured on radiographs. The heights of vertebrae L5, L6 and sacrum were measured on sagittal pQCT slices.

Results: All mice had a significant increase in body length during the experiment, but Scl-Ab-treated oim/oim mice remained significantly shorter than the vehicle-treated animals. Humerus and tibia length was similar in all the groups, without influence of Scl-Ab-treatment. Similar results were obtained in the craniofacial dimensions. In the spine, the sacrum (S1–S3) was significantly shorter in vehicle-treated oim/oim than in vehicle-treated controls (−20%). Individual vertebrae of oim/oim mice showed a non-significant increase in their height with Scl-Ab treatment.

Conclusions: In oim/oim mice, short stature could be due to global vertebral shortening. The absence of an effect of sclerostin antibody on stature could be related to its administration after the rapid growth phase. Future studies will investigate earlier phases of growth.

Declaration of interest: M Ominsky is an employee of Amgen, Inc.