Open AccessInduction of periosteal bone formation by intraosseous BMP-2 injection in a mouse model of osteogenesis imperfecta
Author(s) -
Tegan L. Cheng,
Laurence C. Cantrill,
Aaron Schindeler,
David Little
Publication year - 2019
Publication title -
journal of children's orthopaedics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.638
H-Index - 36
eISSN - 1863-2548
pISSN - 1863-2521
DOI - 10.1302/1863-2548.13.190119
Subject(s) - intramedullary rod , calcein , osteogenesis imperfecta , bone morphogenetic protein , medicine , saline , bone morphogenetic protein 2 , cortical bone , x ray microtomography , long bone , bone healing , anatomy , chemistry , radiology , biochemistry , membrane , gene , in vitro
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 Col1a2 G610C/+ (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.