Modeling anabolic and antiresorptive therapies for fracture healing in a mouse model of osteogenesis imperfecta
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Updated: Aug 8, 2026
A Minimally Invasive Model to Analyze Endochondral Fracture Healing in Mice Under Standardized Biomechanical Conditions
Published on: March 22, 2018
Alexandra K O'Donohue1,2, Aiken Dao1,2, Justin D Bobyn1
1Bioengineering & Molecular Medicine Laboratory, The Children's Hospital at Westmead and the Westmead Institute for Medical Research, Sydney, New South Wales, Australia.
Abstract:
Osteogenesis imperfecta (OI) is a genetic bone fragility disorder that features frequent fractures. Bone healing outcomes are contingent on a proper balance between bone formation and resorption, and drugs such as bone morphogenetic proteins (BMPs) and bisphosphonates (BPs) have shown to have utility in modulating fracture repair. While BPs are used for OI to increase BMD and reduce pain and fracture rates, there is little evidence for using BMPs as local agents for fracture healing (alone or with BPs). In this study, we examined wild-type and OI mice (Col1a2+/G610C ) in a murine tibial open fracture model with (i) surgery only/no treatment, (ii) local BMP-2 (10 µg), or (iii) local BMP-2 and postoperative zoledronic acid (ZA; 0.1 mg/kg total dose). Microcomputed tomography reconstructions of healing fractures indicated BMP-2 was less effective in an OI setting, however, BMP-2 +ZA led to considerable increases in bone volume (+193% WT, p < 0.001; +154% OI, p < 0.001) and polar moment of inertia (+125% WT, p < 0.01; +248% OI, p < 0.05). Tissue histology revealed a thinning of the neocortex of the callus in BMP-2 treated OI bone, but considerable retention of woven bone in the healing callus with BMP + ZA specimens. These data suggest a cautious approach may be warranted with the sole application of BMP-2 in an OI surgical setting as a bone graft substitute. However, this may be overcome by off-label BP administration.
Insights
Combining bone morphogenetic proteins-2 (BMP-2) with zoledronic acid (ZA) improved fracture healing in osteogenesis imperfecta (OI) mice. Sole BMP-2 application was less effective, suggesting caution for OI fracture repair.
Area of Science:
- Orthopedics
- Genetics
- Biomaterials
Background:
- Osteogenesis imperfecta (OI) is a genetic disorder causing bone fragility and frequent fractures.
- Effective fracture healing requires balancing bone formation and resorption.
- Bone morphogenetic proteins (BMPs) and bisphosphonates (BPs) can modulate fracture repair, but BMPs' role in OI fracture healing is understudied.
Purpose of the Study:
- To investigate the efficacy of local bone morphogenetic protein-2 (BMP-2) alone and in combination with zoledronic acid (ZA) for enhancing fracture healing in a murine model of osteogenesis imperfecta (OI).
Main Methods:
- A murine tibial open fracture model was used with wild-type and OI mice (Col1a2+/G610C).
- Treatment groups included surgery only, local BMP-2 (10 µg), and local BMP-2 with postoperative zoledronic acid (ZA; 0.1 mg/kg).
- Microcomputed tomography and tissue histology were employed to assess bone healing outcomes.
Main Results:
- Local BMP-2 was less effective in promoting fracture healing in the OI model compared to wild-type.
- The combination of BMP-2 and ZA significantly increased bone volume and polar moment of inertia in both wild-type and OI mice.
- Histology showed thinning of the neocortex with BMP-2 alone in OI, while BMP-2 + ZA retained woven bone in the healing callus.
Conclusions:
- Sole application of BMP-2 as a bone graft substitute may require a cautious approach in OI surgical settings.
- Combining BMP-2 with zoledronic acid demonstrates potential for improving fracture healing in OI.
- Off-label bisphosphonate administration may overcome limitations of BMP-2 monotherapy in OI fracture repair.
