The original guiding principle underlying skeletal
adaptation as a result of physical exercise is referred to as
Wolff’s Law, which states that bone accommodates to the
forces applied to it by altering its amount and distribution
of mass to withstand future loads of similar nature
(see also Chapters 1 and 19) [57]. While several theories
have been proposed to explain how bones respond to
changes in loading, Frost’s mechanostat theory proposes
that bones have a set-point or threshold level for
adaptation called the minimum effective strain (MES) [58]
(Fig. 29.2). Under normal physiological loading conditions
where strain does not exceed a given threshold, no
adaptive response occurs and bone mass and strength
is maintained. In contrast, if strains exceed an upper
threshold or set-point (∼1500–2500 microstrain (μE)),
new bone formation is initiated to provide resistance
to further deformation and reduce the strains to within
the optimal physiological range. Conversely, when customary
loading strain is reduced, as occurs during bed
rest or a microgravity environment, there is a rapid and
dramatic loss in bone. While it has been suggested that
the MES set-points are genetically controlled, Figure
29.2 also shows that estrogen deficiency can alter the
response to loading reducing the amount of new bone
formation. Furthermore, it has been suggested that the
MES becomes less sensitive during old age