Remodeling of fracture callus in mice is consistent with mechanical loading and bone remodeling theory

Abstract

During the remodeling phase of fracture healing in mice, the callus gradually transforms into a double cortex, which thereafter merges into one cortex. In large animals, a double cortex normally does not form. We investigated whether these patterns of remodeling of the fracture callus in mice can be explained by mechanical loading. Morphologies of fractures after 21, 28, and 42 days of healing were determined from an in vivo mid-diaphyseal femoral osteotomy healing experiment in mice. Bone density distributions from microCT at 21 days were converted into adaptive finite element models. To assess the effect of loading mode on bone remodeling, a well-established remodeling algorithm was used to examine the effect of axial force or bending moment on bone structure. All simulations predicted that under axial loading, the callus remodeled to form a single cortex. When a bending moment was applied, dual concentric cortices developed in all simulations, corresponding well to the progression of remodeling observed experimentally and resulting in quantitatively comparable callus areas of woven and lamellar bone. Effects of biological differences between species or other reasons cannot be excluded, but this study demonstrates how a difference in loading mode could explain the differences between the remodeling phase in small rodents and larger mammals.

Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

“…In the longitudinal view, the edge of the callus was seen where the original bone bifurcates into two surfaces of bone. Another study by Isaksson et al (2008) investigated remodelling of fracture callus in mice. Their experimental model also demonstrated formation of a double cortex during remodelling phase of healing.…”

Impairment of the chondrogenic phase of endochondral ossification in vivo by inhibition of cyclooxygenase-2

“…Boundary conditions were applied to represent an axial compression test, an axial torsion test and bending tests in two orthogonal directions. Then, for each test the stiffness of the scanned region was determined (units: N/mm for the compression tests and Nmm/rad for the torsion/bending tests) (Isaksson et al, 2009;van Rietbergen et al, 1998).…”

Survival of the Less-fit: A Least Shrew (Mammalia, Soricidae, Cryptotis parvus) Survives a Separated Leg Fracture in the Wild

“…Surrounding nearly the entire diaphysis is a large, relatively thin-walled external callus, the bony margin of which represents a greatly enlarged external wall of a double cortex similar to that described by Isaksson et al (2009). The callus contains abundant trabecular bone, which probably provided structural support in the absence of bridging and healing of the diaphysis.…”

“…Experiments investigating fracture repair in laboratory mouse models indicate that fractures in small mammals can heal relatively rapidly (Manigrasso and O'Connor, 2004;Isaksson et al, 2009). External callus forms by 7 days and reaches peak volume 10-21 days postfracture.…”