The putitive bone-sparing effect of
alendronate was tested in two animal models of
osteopenia:
estrogen-deficient female rats and
glucocorticoid-treated male rats. In the first study, 18 female Sprague-Dawley rats, 4 months of age, were ovariectomized (OVX), and an additional 6 rats were
sham-operated. The OVX rats were treated with either vehicle, 17beta-estradiol (E2) (100 microg/rat/week, s.c.), or
alendronate (1 mg/kg/day, on alternate days, orally). In the second study, 24 8-month-old male Wistar rats were treated with either vehicle, methyl
prednisolone (7 mg/kg once a week, s.c.),
prednisolone plus
testosterone (16 mg/kg once every 3 weeks, i.m.), or
prednisolone plus
alendronate (20 microg/kg twice a week, s.c.). Prior to treatment and at the end of the 6-week treatment period, bone mineral density (BMD) of the lumbar spine was measured by dual energy x-ray absorptiometry, and mean femur weights were calculated. The OVX rats had subnormal BMD (-3.91 +/- 1.0% vs control +5.19 +/- 3.92%, P < 0.05) and femur weights (720 +/- 6 mg vs %; 746 +/- 11 mg, P < 0.05). OVX-induced bone loss was completely abolished by the administration of E2 (7.01 +/- 2.32%, P < 0.005; 748 +/- 6 mg, P < 0.01), or
alendronate (24.2 +/- 2.73%, P < 0.0001; 779 +/- 11 mg, P < 0.001). In the second study in older male rats,
glucocorticoids significantly decreased BMD (-9.70 +/- 3.44% vs -1.10 +/- 1.75%, P < 0.05), and femur weight (1070 +/- 14 mg vs 1180 +/- 24 mg, P < 0.01). Concomitant administration of
testosterone (BMD 4.23 +/- 1.84%, P < 0.005; femur weight 1260 +/- 56 mg, P < 0.02), or
alendronate (BMD 8.18 +/- 1.36%, P < 0.001; femur weight 1360 +/- 50 mg) with
prednisolone, abolished the
corticosteroid-induced bone loss. Bone histomorphometry showed a 34% loss of trabecular bone volume in
glucocorticoid-treated rats (P < 0.05), which was prevented with both
testosterone and
alendronate therapies. However, at the doses used in both models,
alendronate was more efficacious than either E2 or
testosterone in increasing BMD and femur weight. In summary, this study demonstrated that
alendronate therapy is highly effective in counteracting the
osteopenia of OVX and
glucocorticoid therapy.