TY - JOUR
T1 - Murine model of oligotrophic tibial nonunion
AU - Hu, Calvin T.
AU - Offley, Sarah C.
AU - Yaseen, Zaneb
AU - O'Keefe, Regis J.
AU - Humphrey, Catherine A.
PY - 2011/8
Y1 - 2011/8
N2 - Objectives: This study aimed to use modified distraction osteogenesis techniques to develop a reliable mouse fracture nonunion model with an oligotrophic phenotype. Methods: Twenty-six 10- to 14-week-old C57BL/6 male mice underwent a proximal diaphyseal tibial osteotomy with a 2-mm bone resection. An external fixation device was applied to the tibia using cerclage wires. A total of 2.25 mm of distraction was applied over 3 days, resulting in an average distraction gap of 4.28 mm. Plain radiographs were taken at regular intervals until euthanasia at 7 (n = 9), 10 (n = 13), or 12 (n = 4) weeks. After euthanasia, all samples were fixed in formalin, scanned with microcomputed tomography, decalcified in formic acid, prepared in paraffin, and stained with Alcian blue/Mayer's hematoxylin. Results: In the distraction groups, five mice were prematurely euthanized as a result of wound complications stemming from loss of distal fixation. Of the remaining 21, two healed, resulting in a 90% nonunion rate. These nonunions radiographically resembled clinical nonunions with tapered, cone-like fracture ends and histologically demonstrated evidence of attempted healing as seen with cartilage capping. Additionally, the plain radiographic appearance of those nonunions from mice euthanized at 10 and 12 weeks did not change over the final 4 to 6 weeks. Conclusions: The use of 2-mm tibial resection osteotomy with 2-mm distraction provides a predictable model for fracture nonunion in mice with the oligotrophic phenotype closely resembling the clinical correlate. This model offers a promising means for characterization of the molecular events that occur during the development of fracture nonunion and for evaluation of noninvasive methods of nonunion rescue.
AB - Objectives: This study aimed to use modified distraction osteogenesis techniques to develop a reliable mouse fracture nonunion model with an oligotrophic phenotype. Methods: Twenty-six 10- to 14-week-old C57BL/6 male mice underwent a proximal diaphyseal tibial osteotomy with a 2-mm bone resection. An external fixation device was applied to the tibia using cerclage wires. A total of 2.25 mm of distraction was applied over 3 days, resulting in an average distraction gap of 4.28 mm. Plain radiographs were taken at regular intervals until euthanasia at 7 (n = 9), 10 (n = 13), or 12 (n = 4) weeks. After euthanasia, all samples were fixed in formalin, scanned with microcomputed tomography, decalcified in formic acid, prepared in paraffin, and stained with Alcian blue/Mayer's hematoxylin. Results: In the distraction groups, five mice were prematurely euthanized as a result of wound complications stemming from loss of distal fixation. Of the remaining 21, two healed, resulting in a 90% nonunion rate. These nonunions radiographically resembled clinical nonunions with tapered, cone-like fracture ends and histologically demonstrated evidence of attempted healing as seen with cartilage capping. Additionally, the plain radiographic appearance of those nonunions from mice euthanized at 10 and 12 weeks did not change over the final 4 to 6 weeks. Conclusions: The use of 2-mm tibial resection osteotomy with 2-mm distraction provides a predictable model for fracture nonunion in mice with the oligotrophic phenotype closely resembling the clinical correlate. This model offers a promising means for characterization of the molecular events that occur during the development of fracture nonunion and for evaluation of noninvasive methods of nonunion rescue.
KW - distraction osteogenesis
KW - endochondral ossification
KW - external fixation
KW - fracture
KW - mouse
KW - nonunion
KW - oligotrophic
KW - periosteum
UR - http://www.scopus.com/inward/record.url?scp=80051551646&partnerID=8YFLogxK
U2 - 10.1097/BOT.0b013e3182249fad
DO - 10.1097/BOT.0b013e3182249fad
M3 - Article
C2 - 21738067
AN - SCOPUS:80051551646
SN - 0890-5339
VL - 25
SP - 500
EP - 505
JO - Journal of orthopaedic trauma
JF - Journal of orthopaedic trauma
IS - 8
ER -