Biomedical Engineering Reference
In-Depth Information
An alternative approach to the use of chronologically aged animals is the use of
mice that have an early aging (senescence) phenotype. Several such models relevant
to bone have been described. We utilized the P6 strain of the senescence accelerated
mouse (SAMP6), which has features reminiscent of age-related osteopenia. For
example, as early as 4 months age SAMP6 mice have enlarged periosteal and en-
docortical diameters, reduced trabecular bone volume, reduced endosteal bone
formation rate, reduced marrow osteogenesis, and reduced resistance to fracture
(fracture energy) compared to SAMR1 control mice [
47
-
50
]. Nevertheless, when
loaded by in vivo tibial three-point bending (1000-2000 le, 60 cycles/day, 2 weeks)
endocortical bone formation was activated by a similar amount in both SAMP6
(senescent) and SAMR1 (control) mice. We concluded that there was ''little evi-
dence of diminished responsiveness to loading in the SAMP6 skeleton'' [
51
]. The
use of the SAMP6 mouse is not a substitute for studies of chronologically aged
animals, and we no longer advocate use of this model [
52
]. Nonetheless, the results of
our loading study support the view that responses to loading are not necessarily
compromised by a relatively low level of baseline bone formation or pre-existing
osteopenia, conditions that occur with aging.
4.3 Tibial Cantilever Bending
Gross et. al developed a cantilever bending model that applies a transverse load to
the distal end of the tibia while the proximal end at the knee joint is clamped [
22
].
The strain at the mid-diaphysis is modulated by controlling the magnitude of the
applied load. A strength of the model is that it does not involve direct contact
between the loading surface and the bone surface of interest (in contrast to four-
point tibial bending). One limitation is that the applied load is not transmitted
through the metaphyseal region and hence the modality does not lend itself to
study trabecular bone adaptation. The loading direction is different from that
associated with normal physiological activities, which might be viewed as a
strength or limitation.
Srinivasan et al. [
53
] applied cantilever tibial bending to old (22 month) mice
and concluded that it was possible to induce an anabolic bone response, but that old
mice were less responsive than young (4 month) mice. (The results of the young
mice are mentioned in the Discussion only, and appear to have been obtained in a
separate, previous experiment by the same authors.) The rate of periosteal bone
formation induced in old mice by ''low-magnitude'' rest-inserted loading (1200 le,
50 cycles/day, 10 s rest interval between load cycles) was nearly 2.5-fold less than
that induced by a similar protocol in young mice. In addition, old mice did not
demonstrate a further increase in bone formation rate when loading magnitude was
doubled (2400 le), contrary to findings in young animals. The authors suggested
that a deficit in the number of available osteoblasts that can be activated might be
the reason for the inability of old mice to respond to higher loads.
Search WWH ::
Custom Search