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Models of tibial fracture healing in normal and Nf1-deficient mice.

Schindeler, Aaron and Morse, Alyson and Harry, Lorraine and Godfrey, Craig and Mikulec, Kathy and McDonald, Michelle and Gasser, Juerg Andreas and Little, David G (2008) Models of tibial fracture healing in normal and Nf1-deficient mice. Journal of Orthopaedic Research : official publication of the Orthopaedic Research Society, 26 (8). pp. 1053-1060. ISSN 1554-527X

Abstract

Delayed union and nonunion are common complications associated with tibial fractures, particularly in the distal tibia. Existing mouse tibial fracture models are typically closed and middiaphyseal, and thus poorly recapitulate the prevailing conditions following surgery on a human open distal tibial fracture. This report describes our development of two open tibial fracture models in the mouse, where the bone is broken either in the tibial midshaft (mid-diaphysis) or in the distal tibia. Fractures in the distal tibial model showed delayed repair compared to fractures in the tibial midshaft. These tibial fracture models were applied to both wild-type and Nf1-deficient (Nf1+/-) mice. Bone repair has been reported to be exceptionally problematic in human NF1 patients, and these patients can also spontaneously develop tibial nonunions (known as congenital pseudarthrosis of the tibia), which are recalcitrant to even vigorous intervention. pQCT analysis confirmed no fundamental differences in cortical or cancellous bone in Nf1-deficient mouse tibiae compared to wild-type mice. Although no difference in bone healing was seen in the tibial midshaft fracture model, the healing of distal tibial fractures was found to be impaired in Nf1+/- mice. The histological features associated with nonunited Nf1+/- fractures were variable, but included delayed cartilage removal, disproportionate fibrous invasion, insufficient new bone anabolism, and excessive catabolism. These findings imply that the pathology of tibial pseudarthrosis in human NF1 is complex and likely to be multifactorial.

Item Type: Article
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Additional Information: archiving not allowed on institutional repository
Keywords: fracture healing; neurofibromatosis type I; NF1; congenital pseudarthrosis of the tibia; CPT
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Date Deposited: 14 Dec 2009 13:53
Last Modified: 31 Jan 2013 01:06
URI: https://oak.novartis.com/id/eprint/813

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