Comparable outcomes in fracture reduction and bone properties with RANKL inhibition and alendronate treatment in a mouse model of osteogenesis imperfecta.
Academic Article
Overview
abstract
UNLABELLED: We report a direct comparison of receptor activator of nuclear factor kappa B ligand (RANKL) inhibition (RANK-Fc) with bisphosphonate treatment (alendronate, ALN) from infancy through early adulthood in a mouse model of osteogenesis imperfecta. Both ALN and RANK-Fc decreased fracture incidence to the same degree with increases in metaphyseal bone volume via increased number of thinner trabeculae. INTRODUCTION: The potential therapeutic benefit of RANKL inhibitors in osteogenesis imperfecta (OI) is under investigation. We report a direct comparison of RANKL inhibition (RANK-Fc) with bisphosphonate treatment (ALN) from infancy through early adulthood in a model of OI, the oim/oim mouse. METHODS: Two-week-old oim/oim, oim/+, and wildtype (+/+) mice were treated with RANK-Fc 1.5 mg/kg twice per week, ALN 0.21 mg/kg/week or saline (n = 12-20 per group) for 12 weeks. RESULTS: ALN and RANK-Fc both decreased fracture incidence (9.0 ± 3.0 saline 4.4 ± 2.7 ALN, 4.3 ± 3.0 RANK-Fc fractures per mouse). Serum TRACP-5b activity decreased to 65% after 1 month in all treated mice, but increased sacrifice with RANK-Fc to 130-200% at sacrifice. Metaphyseal density was significantly increased with ALN in +/+ and oim/oim mice (p < 0.05) and tended to increase with RANK-Fc in +/+ mice. No changes in oim/oim femur biomechanical parameters occurred with treatment. Both ALN and RANK-Fc significantly increased trabecular number (3.73 ± 0.77 1/mm for oim/oim saline vs 7.93 ± 0.67 ALN and 7.34 ± 1.38 RANK-Fc) and decreased trabecular thickness (0.045 mm ± 0.003 for oim/oim saline vs 0.034 ± 0.003 ALN and 0.032 ± 0.002 RANK-Fc) and separation in all genotypes (0.28 ± 0.08 mm for oim/oim saline vs 0.12 ± 0.010 ALN and 13 ± 0.03 RANK-Fc)., with significant increase in bone volume fraction (BVF) with ALN, and a trend towards increased BVF in RANK-Fc. CONCLUSION: Treatment of oim/oim mice with either a bisphosphonate or a RANK-Fc causes similar decreases in fracture incidence with increases in metaphyseal bone volume via increased number of thinner trabeculae.
