Biomedical Engineering Reference
In-Depth Information
1 Introduction
The interdependence of skeletal form and function has been the subject of much
scientific inquiry. Early observations on bone growth and adaptation in response to
functional loading were made by Roux in 1881, and formally described by Wolff
in 1890. 'Wolff's law' entails two important concepts regarding bone adaptation:
optimization of bone strength to weight, and remodeling of bone under the
influence of functional loading [
1
]. A proposal to put these observations regarding
bone adaptation into a quantitative framework was made by Carter [
2
], who noted
that cyclic strain history governs adaptation with different control mechanisms for
disuse versus overuse. Frost put forth a similar framework in the form of his
mechanostat hypothesis: bone adds mass if the habitual load increases above a
certain threshold and loses mass if the habitual load decreases below certain
threshold [
3
]. In the last few decades numerous experiments were carried out to
better understand how the different parameters of loading influence bone adapta-
tion. Some common ''rules'' have emerged from these experiments: the local strain
history is a key determinant of the tissue response; dynamic rather than static
strains drive bone adaptation; the dynamic strain magnitude required to initiate an
adaptive response decreases with increasing loading frequency; few loading cycles
are sufficient to trigger bone adaptation provided the strain magnitude is above an
adaptation threshold; bone reaches a new homeostasis state in response to altered
loading history and further loading at similar magnitude fails to invoke an addi-
tional response [
4
-
6
]. Although much progress has been made, most animal
studies have focused on external variables and have utilized young animals. We
have a very limited understanding of the influence of age, or other intrinsic
parameters, on loading-induced bone adaptation.
Skeletal physiology and/or bone mechano-responsiveness is potentially influ-
enced by a variety of systemic and local changes associated with aging. For
instance the number of osteocytes, the cell type proposed to be involved with bone
mechano-transduction, appears to decrease with aging [
7
-
9
]. The loss of muscle
mass and strength with age (sarcopenia) may also contribute to age-related bone
loss, either through common regulatory factors such as insulin-like growth factor 1
(IGF1) or simply because weaker muscles generate less skeletal loading [
10
,
11
].
Aging is also associated with changes in vascular function and blood flow that
could potentially influence shear stress or chemotransport dependent transduction
mechanisms. Moreover, levels of various systemic hormones and local cytokines
are influenced by aging. Considering such systemic and local factors, it is natural
to inquire if and how aging affects the ability of bone to adapt in response to its
mechanical environment.
The issue of how aging affects skeletal responses to mechanical stimuli
carries clinical implications. After peak bone mass is attained in young
adulthood/maturity (*30 years age), net deficits in bone turnover are observed
in both men and women that result in progressive loss of bone mass. The loss
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