Comparison of bone loss induced in female rats by hindlimb unloading, ovariectomy, or both

Clinical and experimental evidence supports a link between the effects of mechanical loading and those of estrogens on bone. The objective of this study was to compare bone loss induced in female rats by hindlimb unloading, ovariectomy, or both.

Thirty-six female Wistar rats aged 12 weeks were randomized to bilateral surgical ovariectomy without tail suspension (OV) or with tail suspension for 30 days (OV-TS) or to sham surgery without tail suspension (control group, C) or with tail suspension for 30 days (TS). Bone mineral density (BMD) of the distal femoral metaphysis was measured in g/cm2 by dual X-ray absorptiometry in all 12 animals on days 0, 7, 14, and 30.

On D14 and D30, BMD (mean+/-S.D.) was significantly lower in the OV, TS, and OV-TS groups than in the control group (D14: 0.239+/-0.014, 0.243+/-0.016, and 0.227+/-0.018, respectively, vs. 0.258+/-0.005 in the controls; P<0.05; and D30: 0.241+/-0.011, 0.227+/-0.015, and 0.200+/-0.018, respectively, vs. 0.279+/-0.009 in the controls; P<0.001). On D30, the percentage BMD change versus baseline (mean+/-S.D.) differed significantly between the combination (OV-TS) group (-14.26+/-8.14) and the single-intervention groups (OV: +0.99+/-6.44, P<0.001; and TS: -6.36+/-4.56, P<0.05). As early as D7, bone loss was significantly greater in the combination (OV + TS) group than in the OV group (-1.79%+/-7.17 vs. +4.29%+/-9.55; P<0.05).

In female rats, the rate and severity of bone loss were greater when estrogen deprivation was combined with mechanical unloading than when either intervention was used alone. Mechanical unloading induced a greater degree of bone loss than did estrogen deprivation. In this model of high-rate bone loss, mechanical unloading may predominate over estrogen deprivation in the genesis of bone loss.