The Effect of Aging on Skeletal Mechanoresponsiveness: Animal Studies - Skeletal Aging and Osteoporosis: Biomechanics and Mechanobiology - page 207

4.6 Summary: Bone Responses to Extrinsic
Mechanical Loading
We found only seven animal studies of extrinsic mechanical loading that directly
compared different ages, and only four of these included a true old age group
(Table 3 ). Of these four, three reported a negative influence of age and one a
neutral-to-positive influence. We note that three of the four studies did report an
anabolic response in old animals, indicating that it was possible to elicit a
mechanoresponse, although perhaps diminished. Taken together, the limited
available data indicate that with aging there is a decline—but not a loss—in
skeletal mechanoresponsiveness to extrinsic loading.
5 Skeletal Unloading
Whereas increased skeletal loading can stimulate bone formation and increase
bone mass, diminished skeletal loading can stimulate bone resorption and lead to
decreased bone mass, sometimes called disuse osteopenia. Astronauts, paraplegic
and quadriplegic patients, and trained athletes after de-training all demonstrate
significant bone loss as a result of reduction in the skeleton's functional demands.
Unloading related bone loss is more pronounced in skeletal sites that experience
higher habitual loads and/or sites that are closer to the ground, perhaps because of
fluid pressure effects [ 6 ]. Also trabecular bone shows much more rapid loss
compared to cortical bone. A better understanding of unloading related bone loss
would help us to develop therapies to minimize such bone loss during extended
period of bed rest and paralysis.
The animal models used to study disuse or unloading related bone adaptation
can be broadly classified as invasive or non-invasive. Invasive models include:
nerve resection, tenotomy and bone isolation. Both neurectomy and tenotomy
create disuse by disabling muscle-induced loading. Bone isolation involves
bypassing a part of bone as far as loading is concerned. Non-invasive models
include hindlimb suspension, limb casting/taping, space flight and botulinum toxin
induced muscle paralysis. The non-invasive disuse models, with the exception of
botulinum toxin induced muscle paralysis, do not inhibit muscle induced loading
of the bone and therefore do not interfere with physiological phenomenon asso-
ciated with low-level muscle activity.
Few studies have examined how aging influences unloading related bone loss.
Uhthoff et al. [ 66 ] reported the effects of 60 weeks of cast immobilizations in the
forelimb of young adult (1-3 year) and old (7-8 years) dogs. Bone loss was
greater in trabecular compared to cortical bone, and at distal (metacarpals) com-
pared to proximal (humerus) sites. This pattern was similar in adult and old dogs,
and the magnitude of bone loss was similar in the two age groups although the
young adult dogs lost bone by reduced periosteal expansion whereas older dogs