Skeletal Mechanoresponsiveness: Effects of Sex Hormones - Skeletal Aging and Osteoporosis: Biomechanics and Mechanobiology - page 220

bone loss in ORX mice [ 28 ]. In growing (2-months) mice, 17b-estradiol alone
completely prevented OVX- and ORX-induced cancellous bone loss in the femur
[ 28 , 54 ].
2.2 Hormone Deficiency and Direct Skeletal Loading
In contrast to exercise models of skeletal loading, the mechanical stimulus applied
to the skeleton is quantifiable and accurately controlled with direct (extrinsic)
loading methods. While a large number of studies have combined OVX with
exercise, only limited data are available for direct loading [ 14 , 41 ]. The response
of the tibia to direct skeletal loading by four-point bending of the diaphysis and by
axial compression of the whole hindlimb has been examined with sex hormone
deficient animals. The target strain range in the cortex with loading is gener-
ally *1200-1300 le, corresponding to locomotory strains measured across a
range of species [ 55 ].
Direct loading of the tibia inhibits bone loss with hormone deficiency. Tibial
four-point bending of adult (6-months) OVX and sham rats increased cortical area
through equivalent dynamic measures of bone formation [ 14 ]. Similar loads were
applied to OVX and sham rats (31.4 N), producing mean strains of *1300 le in
both groups. The cortical bone response to loading was not altered with OVX and
the absence of endogenous estrogen. Likewise, 6 weeks of cyclic tibial com-
pression, producing 1200 le at the tibial midshaft of mice, inhibited bone loss after
ORX and maintained absolute bone mass at age-matched sham control levels in
growing (2-months) mice [ 41 ]. ORX decreased cancellous bone volume fraction
and trabecular number, increased trabecular separation, and did not change tra-
becular thickness. Metaphyseal cancellous bone volume was greater with loading
than in contralateral nonloaded tibia, due to trabecular thickening with loading.
Loading was associated with greater mineral apposition rates and smaller percent
mineralizing surfaces. Cortical mass decline was less severe than cancellous bone
loss with ORX, but diaphyseal cortical properties were reduced compared to sham
surgery mice. In cortical bone, loading increased BMC and maximum moment of
inertia similarly in both sham and ORX mice. In vivo tibial compression increased
cancellous and cortical bone mass in osteopenic OVX adult female mice after
6 weeks of loading (unpublished data). In OVX mice, cancellous bone mass in
loaded limbs exhibited a bimodal distribution with time due to the competing
effects of loading and estrogen deficiency. Adult (6-months old) C57Bl/6 mice
were osteopenic, and estrogen deficiency did not further reduce cortical bone
mass. The ability of the skeleton to adapt to mechanical loading was unaltered with
OVX. As in exercise studies, the ability to form bone with direct skeletal
loading does not require endogenous estrogen and is similar in intact and hormone-
deficient mice.