The effect of ovariectomy combined with hindlimb unloading and reloading on the long bones of mature Sprague-Dawley rats

Abstract

To determine the effect of loss of ovarian function and mechanical loading (ie, inactivity) alone or in combination on bone mass and strength. Mature (aged 6 mo) rats were ovariectomized to induce loss of ovarian function and bone. Hindlimb unloading (HLU) was used to determine the effect of mechanical unloading and reloading on bone mass and strength. Bone mass of the femur and tibia was determined using dual-energy x-ray absorptiometry. Femoral and tibial bone strength was determined by a three-point bending test and by a torsion test. Ovariectomy (OVX) alone decreased total bone mineral density (BMD) in the femur (-5.5%, P=0.03) and tibia (-7.3%, P=0.01) compared with that for sham-operated animals. HLU alone for 4 weeks had no significant effect on bone. Together OVX/HLU accentuated BMD loss in the femur (-10.5%, P<0.01) compared with that for sham-operated animals. The femur was more sensitive than the tibia to the combination of OVX/HLU, indicated by the reduction (-5.3%, P<0.05) of total BMD below that achieved by OVX alone. Torsion tests showed that OVX/HLU but not OVX or HLU alone reduced bone strength. There was a correlation between lower femoral total BMD (r2=0.65, P<0.001) and reduced torque strength. Bone loss did not continue during the 2 weeks of reloading. OVX accompanied by mechanical unloading results in more rapid and severe bone loss than either OVX or unloading alone and therefore is associated with a greater likelihood of osteoporosis.