Induction of periosteal bone formation by intraosseous BMP-2 injection in a mouse model of osteogenesis imperfecta

Author:

Cheng T. L.12,Cantrill L. C.23,Schindeler A.12,Little D. G.12

Affiliation:

1. Orthopaedic Research and Biotechnology Unit, Children’s Hospital at Westmead, Sydney, NSW, Australia

2. Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia

3. Microscopy Services at Kids Research, The Children’s Hospital at Westmead, Sydney, NSW, Australia

Abstract

Purpose Surgical interventions are routinely performed on children with osteogenesis imperfecta (OI) to stabilize long bones, often post fracture. We speculated that a combination of intramedullary reaming and intraosseous injection of recombinant bone morphogenetic protein-2 (BMP-2) could enhance periosteal ossification and ultimately cortical thickness and strength. This approach was conceptually tested in a preclinical model of genetic bone fragility. Methods Six experimental groups were tested including no treatment, intramedullary reaming, and reaming with 5 µg BMP-2 injection performed in the tibiae of both wild type (WT) and Col1a2G610C/+ (OI, Amish mutation) mice. Bone formation was examined at a two-week time point in ex vivo specimens by micro-computed tomography (microCT) analysis and histomorphometry with a dynamic bone label. Results MicroCT data illustrated increases in tibial cortical thickness with intramedullary reaming alone (Saline) and reaming plus BMP-2 injection (BMP-2) compared to no intervention controls. In the OI mice, the periosteal bone increase was not statistically significant with Saline but there was an increase of +192% (p = 0.053) with BMP-2 injection. Dynamic histomorphometry on calcein label was used to quantify new woven bone formation; while BMP-2 induced greater bone formation than Saline, the anabolic response was blunted overall in the OI groups. Conclusions These data indicate that targeting the intramedullary compartment via reaming and intraosseous BMP-2 delivery can lead to gains in cortical bone parameters. It is suggested that the next step is to validate safety and functional improvements in a clinical OI setting.

Publisher

SAGE Publications

Subject

Orthopedics and Sports Medicine,Pediatrics, Perinatology and Child Health

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