Biomedical Engineering Reference
In-Depth Information
4.4 Axial Tibial Compression
Axial compression of the hindlimb was developed separately by Fritton et al. [
54
]
and de Souza et al. [
55
] as a non-invasive method to stimulate bone formation in
the mouse tibia. The hindlimb of the animal is secured between supports at the
knee and foot; controlled compressive load is applied through these supports, in
the direction of the long axis of the tibia. Since the supports do not contact the
periosteal surface of the bone, adaptation of the entire length of the tibia including
cortical bone at the diaphysis and trabecular bone at the proximal metaphysis can
be studied. Strain gage and finite element analysis methods have been used to
characterize force-strain relationships and strain distributions at the mid-diaphysis
[
55
,
56
]. Owing to the natural curvature of the tibia, a combined compression-
bending loading state is generated in the mid-diaphysis. This results in compres-
sive strains near the postero-lateral apex of the tibial cross-section with tensile
strains on the antero-medial flat. However, characterization of strain distribution
in trabecular region of metaphysis under applied loading remains a challenge.
Currently, this is one on the most popular extrinsic models used to study bone
adaptation.
We compared the response of mature (7 months) and old (22 months) male,
BALB/c mice to axial tibial compression, with a focus on cortical bone [
57
].
BALB/c mice represent an intermediate bone mass strain. Legs were loaded at one
of three force levels (range 900-1900 le endocortical, 1400-3100 le periosteal;
60 rest-inserted cycles/day, 5 days). Mice from both age groups showed a strong
anabolic response at the mid-diaphysis. At the endocortical surface, aged mice had
a significantly greater response to loading than mature mice while responses at
the periosteal surface did not differ between age groups (Fig.
2
). We concluded
that aging does not limit the short-term anabolic response of cortical bone to
mechanical stimulation in this animal model.
In a follow-up study, we examined female, BALB/c mice ranging in age from
young to middle-aged (2, 4, 7, 12 months) [
58
]. Using analysis of serum and bone
mRNA in mice not subjected to loading, we noted an age-related decline in
markers of bone formation, corresponding with the transition from growth to
skeletal maturity. We then performed axial tibial compression (*1300 le
endocortical, *2400 le periosteal; 60 rest-inserted cycles/day, 3 days/week) and
evaluated changes in gene expression by qRT-PCR after 1 week of loading. Bone
formation related genes [e.g., type 1 collagen (Col1a1), osteocalcin (Bglap)] were
upregulated in an age-dependent manner; younger mice did not show evidence of
an increase whereas the expression in the loaded tibias of older mice increased to
levels seen in young mice. Finally, we performed 6 weeks of loading in another set
of young to middle-aged mice and followed changes in bone structure by in vivo
microCT. Loaded tibias in each age group had significantly greater cortical bone
volume (BV) than contralateral control tibias, due to relative periosteal expansion.
The loading-induced increase in BV was greatest in 4-month old mice, suggesting
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