Treatment with risedronate or alendronate prevents hind-limb immobilization-induced loss of bone density and strength in adult female rats

Immobilization leads to rapid loss of bone mass and mechanical competence, and long-term immobilization or repeated periods of short-term immobilizati on can have serious skeletal consequences and may lead to increased fractur e liability. The aim of the present preclinical study was, therefore, to as sess whether two antiresorptive agents, risedronate (Ris) or alendronate (A ln), would be capable of preventing immobilization-induced loss of bone mas s and strength in rats. The study was designed as a dose-response study, an d the site-specific effects of immobilization and of treatment are describe d, Four-month-old virgin female Sprague-Dawley rats were divided into eight groups with 12 animals in each group: (1) immobilized (Imm) control; (2) n ormal control; (3) Imm + Ris 0.1 mg/kg body weight/day (b.w./day); (4) Imm + Ris 0.2 mg/kg b.w./day; (5) Imm + Ris 1.0 mg/kg b.w./day; (6) Imm + Aln 0 .2 mg/kg b.w./day; (7) Imm + Aln 1.0 mg/kg b.w./day; and (8) Imm + Aln 2.0 mg/kg b.w./day, In groups 1 and 3-8, the right hind leg was immobilized wit h an elastic bandage. The study period was 28 days. The effects of unilater al hind-limb immobilization and of treatment were determined by dual-energy X-ray absorptiometry (DEXA) measurements on tibiae and by biomechanical te sting of femora at three different sites: diaphysis; femoral neck; and dist al metaphysis, Bilateral measurements were performed ton the immobilized an d nonimmobilized legs), Immobilization induced a significant loss of bone m ineral density (BMD) at the proximal tibial metaphysis, but no change at th e middiaphysis. Furthermore, immobilization induced a loss of bone strength at the two femoral metaphyses, but no change was seen in three-point bendi ng of the diaphysis, Both risedronate and alendronate treatment showed a do se-dependent protection against the immobilization-induced loss of bone den sity and strength at the metaphyses. We conclude that, in rats, short-term hind-limb immobilization affects only the metaphyses and that no changes ar e seen in the diaphysis, Both risedronate and alendronate can prevent immob ilization-induced bone loss at the metaphyses. The present study confirms t he importance of examining several skeletal sites when testing the efficacy of therapeutic agents. (C) 2000 by Elsevier Science Inc. All rights reserv ed.