PREVENTION OF CORTICOSTEROID-INDUCED BONE LOSS WITH ALENDRONATE

The putitive bone-sparing effect of alendronate was tested in two anim al models of osteopenia: estrogen-deficient female rats and glucocorti coid-treated male rats. In the first study, 18 female Sprague-Dawley r ats, 4 months of age, were ovariectomized (OVX), and an additional 6 r ats were sham-operated. The OVX rats were treated with either vehicle, 17 beta-estradiol (E-2) (100 mu g/rat/week, sc), or alendronate (1 mg /kg/day, on alternate days, orally). In the second study, 24 8-month-o ld male Wistar rats were treated with either vehicle, methyl prednisol one (7 mg/kg once a week, sc), prednisolone plus testosterone (16 mg/k g once every 3 weeks, im), or prednisolone plus alendronate (20 mu g/k g twice a week, sc), Prior to treatment and at the end of the 6-week t reatment period, bone mineral density (BMD) of the lumbar spine was me asured by dual energy x-ray absorptiometry, and mean femur weights wer e calculated. The OVX rats had subnormal BMD (-3.91 +/- 1.0% vs contro l +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 E-2 (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 s ignificantly 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). Co ncomitant administration of testosterone (BMD 4.23 +/- 1.84%, P < 0.00 5; 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, ab olished the corticosteroid-induced bone loss. Bone histomorphometry sh owed a 34% loss of trabecular bone volume in glucocorticoid-treated ra ts (P < 0.05), which was prevented with both testosterone and alendron ate therapies, However, at the doses used in both models, alendronate was more efficacious than either E-2 or testosterone in increasing BMD and femur weight. In summary, this study demonstrated that alendronat e therapy is highly effective in counteracting the osteopenia of OVX a nd glucocorticoid therapy.