Modeling anabolic and antiresorptive therapies for fracture healing in a mouse model of osteogenesis imperfecta

• DOI: 10.1002/jor.25414
• Publication Date: 2022-07-09T00:04:06Z
• Authors: Alexandra K. O'Do...; Aiken Dao; Justin D. Bobyn; Craig F. Munns; David G. Little; Aaron Schindeler
• Keywords: Zoledronic Acid; Callus

Osteogenesis imperfecta (OI) is a genetic bone fragility disorder that features frequent fractures. Bone healing outcomes are contingent on proper balance between formation and resorption, drugs such as morphogenetic proteins (BMPs) bisphosphonates (BPs) have shown to utility in modulating fracture repair. While BPs used for OI increase BMD reduce pain rates, there little evidence using BMPs local agents (alone or with BPs). In this study, we examined wild-type mice (Col1a2+/G610C ) murine tibial open model (i) surgery only/no treatment, (ii) BMP-2 (10 µg), (iii) postoperative zoledronic acid (ZA; 0.1 mg/kg total dose). Microcomputed tomography reconstructions of fractures indicated was less effective an setting, however, +ZA led considerable increases volume (+193% WT, p < 0.001; +154% OI, 0.001) polar moment inertia (+125% 0.01; +248% 0.05). Tissue histology revealed thinning the neocortex callus treated bone, but retention woven BMP + ZA specimens. These data suggest cautious approach may be warranted sole application surgical setting graft substitute. However, overcome by off-label BP administration.