Biomedical Engineering Reference
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lost bone primarily by endosteal resorption. In slight contradiction, the same
authors reported that ''older dogs appear to lose less bone than young adult dogs
during the same period of immobilization'' [
67
]. Perrien et al. subjected young
(6 month) and old (32 month) male rats to 2 weeks of hindlimb unloading to study
changes at the proximal tibia [
68
]. Trabecular bone volume was significantly
decreased by unloading in young rats; old rats had markedly less trabecular bone
than young rats but this was not diminished further by unloading. On the other
hand, cortical bone mineral density was decreased and cortical porosity increased
by unloading in old but not young rats. Thus, unloading had negative effects on the
skeleton of young and old rats, although it primarily affected trabecular bone in
young animals and cortical bone in old animals.
6 Discussion
Our understanding of skeletal mechano-biology has come a long way from the early
observations by Roux and Wolff, largely due to animal studies that have identified
the loading parameters that most influence adaptation. However, the general rules
regarding bone adaptation are predominantly based on the observations in young
animals, and are predominantly based on cortical outcomes. It is not clear how
aging influences the dependence of bone adaptation on various loading parameters
such as strain magnitude, strain rate, loading frequency, etc. For example,
Srinivasan et al. [
53
] reported that old mice did not exhibit the dose response to
increased strain magnitude that young mice did, whereas we found that old mice did
exhibit a dose response [
57
]. Development of treatment strategies that rely on
modifying the mechanical environment of skeletal tissues for a favorable outcome
will require a better understanding of the interactions between mechanical loading
and the many biological factors that change with aging.
Improved understanding of the cellular/molecular level biophysical and bio-
chemical events involved with the sensing, transduction and response of bone cells
to mechanical stimuli, and data on how aging influences these events would
greatly facilitate the development of aforementioned therapies. For instance it has
been suggested that a deficit in the number of osteoblasts (the effector cell)
accounts for age-related loss of mechano-responsiveness. However, it is not known
if the sensing and transduction mechanisms are active and performing to their full
potential. It might be futile to focus our efforts on developing therapies to over-
come the age-related osteoblast deficit if the sensing and transduction mechanisms
(most likely related to osteocytes) are impaired. It should also be noted that aging
is often accompanied by various pathologies with potential to influence mechan-
ical loading/unloading related bone adaptation, such as diabetes and hypertension.
Studies to explore how such pathologies and aging together influence bone
mechano-responsiveness will prove to be quite challenging and it will likely take
years to understand such interactions.
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