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 immobilization can have serious skeletal consequences and may lead to increased fracture liability. The aim of the present preclinical study was, therefore, to assess whether two antiresorptive agents, risedronate (Ris) or alendronate (Aln), would be capable of preventing immobilization-induced loss of bone mass and strength in rats. The study was designed as a dose-response study, and the site-specific effects of immobilization and of treatment are described. Four-month-old virgin female Sprague-Dawley rats were divided into eight groups with 12 animals in each group: (1) immobilized (Imm) control; (2) normal 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 with an elastic bandage. The study period was 28 days. The effects of unilateral hind-limb immobilization and of treatment were determined by dual-energy X-ray absorptiometry (DEXA) measurements on tibiae and by biomechanical testing of femora at three different sites: diaphysis; femoral neck; and distal metaphysis. Bilateral measurements were performed (on the immobilized and nonimmobilized legs). Immobilization induced a significant loss of bone mineral density (BMD) at the proximal tibial metaphysis, but no change at the mid-diaphysis. Furthermore, immobilization induced a loss of bone strength at the two femoral metaphyses, but no change was seen in three-point bending of the diaphysis. Both risedronate and alendronate treatment showed a dose-dependent protection against the immobilization-induced loss of bone density and strength at the metaphyses. We conclude that, in rats, short-term hind-limb immobilization affects only the metaphyses and that no changes are seen in the diaphysis. Both risedronate and alendronate can prevent immobilization-induced bone loss at the metaphyses. The present study confirms the importance of examining several skeletal sites when testing the efficacy of therapeutic agents.