Biomedical Engineering Reference
In-Depth Information
We propose a few guidelines regarding design and interpretation of experiments
to study the influence of aging on loading/unloading induced bone adaptation.
First, especially in the case of older human subjects or animals that undergo
normal age-related bone loss, intrinsic loading may prevent bone loss rather than
stimulating bone accrual. In these settings, to correctly identify the mechanism
responsible for maintenance of bone health one has to study the temporal changes
at a skeletal site of interest. Temporal changes can be studied either by inclusion of
both baseline and age-matched control groups or by longitudinal in vivo microCT
or by dynamic histomorphometry measurements. Comparison of bone structure
and strength with sedentary controls at the end of the training/loading period does
not provide insight into the mechanism (bone accrual versus prevention of bone
resorption) responsible for the observed differences. Second, consideration should
be given to selection of appropriate age of the animals. To address the issue of
aging-related changes in bone adaptation the animal ages should be selected so as
to represent different stages of the lifespan (Table
1
). As a rule, ages should be
considered relative to median survival age (the typical measure of longevity of
a species). Median lifespan for mice is approximately 24 months, for rats
30 months, and for humans 75 years. Of course these depend on gender, envi-
ronmental factors (e.g., diet) and genetic background (e.g., rat or mouse strain). As
noted above, many studies of ''aging'' do not include old animals! Studies com-
paring young to mature animals are relevant to bone accrual (peak bone mass),
whereas studies comparing mature to old animals are relevant to age-related bone
loss. Third, regarding the choice of loading modality in rodents there appears to be
a consensus toward use of either axial hindlimb (tibial) compression or forelimb
(ulnar) compression. Four- or three-point bending should be avoided due to
aforementioned issues of periosteal contact pressure. Tibial cantilever bending is a
valid model, but in our hands it is more difficult than tibial or ulnar compression.
An important distinction between axial compression versus cantilever bending is
that the former imposes loading in a direction similar to that for habitual loading,
whereas the latter imposes loading in a non-habitual direction. Either might be
suitable depending on the question being asked.
In summary, bone retains the ability to adapt in response to altered loading
environment at old age provided the induced strain level is sufficient. This
observation is supported by studies that have employed both intrinsic and extrinsic
loading modalities. However, the magnitude of the response of the aged skeleton may
be less than the young skeleton, and/or the threshold to trigger a response may be
greater. Given the relatively few studies that directly compare young, mature and old
animals, there remain many unanswered questions about aging and skeletal
mechanoresponsiveness and thus many opportunities to contribute answers.
Acknowledgments We thank Blaine Christiansen and Nilsson Holguin for their thoughtful
reviews of this chapter. We gratefully acknowledge support from the U.S. National Institutes of
Health NIH/NIAMS R01AR047867 and R21AR054371.
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