Bone Abstracts

The oim/oim mouse resembles type III OI. Our study mimics clinical questions: is RANK-Fc as efficacious as ALN in reducing fracture number? Is RANK-Fc safe to administer to children? Is there any advantage to receiving RANK-Fc treatment post adolescence, following no treatment or ALN treatment from infancy through adolescence?

All animal work was done under an IACUC-approval. Mice – n=200, WT or oim/oim. Treatment spanned age 2–26 weeks. Five study arms (n=20/group/genotype): i) saline – 24 weeks ii) ALN – 24 weeks iii) RANK-Fc – 24 weeks iv) saline – 12 weeks then RANK-Fc for 12 weeks and v) ALN – 12 weeks then Rank-Fc for 12 weeks.

At transition, all treatments had reduced fracture number. From transition to sacrifice, oim/oim mice treated with saline averaged 0.9 new fractures. At sacrifice, all oim/oim treatment groups had reduced fracture number. The saline+RANK-Fc group averaged 0.3 new fractures since transition whereas RANK-Fc 24 weeks, ALN+RANK-Fc, and ALN 24 weeks had no new fractures. Delayed fracture remodeling was observed in treated and untreated oim/oim mice.

For oim/oim mice, all four treatments resulted in increased BV/TV% compared to saline 24 weeks.

Micro Ct: in oim/oim mice, treatment with RANK-Fc, ALN+RANK-Fc, and ALN 24 weeks increased cortical BVF compared to saline 24 weeks. In trabecular parameters changes in the WT mirrored those in the oim/oim, treatment with RANK-Fc 24 weeks, ALN+RANK-Fc, and ALN 24 weeks increased trabecular number and BVF and decreased trabecular spacing compared to saline 24 weeks, without changing trabecular thickness. In the oim/oim saline+RANK-Fc reduced trabecular separation compared to saline 24 weeks.

The conclusion is early intervention with antiresorptive agents at a young age is imperative for significant reductions in fracture incidence and sustained increased BVF into adulthood.