Vol. 286, Issue 1, 128-135, July 1998

Effects of Continuous Alendronate Treatment on Bone Mass and Mechanical Properties in Ovariectomized Rats: Comparison with Pamidronate and Etidronate in Growing Rats

Yoshiaki Azuma, Yasuhiro Oue, Hiroshi Kanatani, Tomohiro Ohta, Mamoru Kiyoki and Keiji Komoriya

Pharmacological Research Department, Teijin Institute for Bio-Medical Research, Tokyo, Japan

Alendronate is a potent inhibitor of bone resorption. To investigate the relationship between antiresorptive activity and bone-related side effects, we studied the effect of 2 months of daily alendronate (0.04, 0.2, 1.0 or 5.0 mg/kg/day) treatment on the strength of the femoral shaft and neck and on the bone mass of ovariectomized rats. The p.o. administration regimen began immediately after ovariectomy at 6 weeks of age, and the results were compared with pamidronate (0.2, 1.0 or 5.0 mg/kg/day) or etidronate (5.0, 25.0 or 125.0 mg/kg/day) treatment. In the femoral epiphysis and neck, a preventive effect of alendronate on loss of bone mineral density was observed at the dose of 1.0 mg/kg. The alendronate-treated group did not show significant alteration of the breaking load or the cross-sectional shape of the femoral midshaft. Similar results were obtained in the femoral neck strength and femoral neck geometry. In histomorphometric analysis of tibial metaphyses, alendronate inhibited the ratio of osteoid volume to tissue volume and the mineral apposition rate at a dose of 0.2 mg/kg compared with the ovariectomized control. In contrast, etidronate tended to increase osteoid volume/bone volume at 125 mg/kg. From these results, we conclude that p.o. alendronate-treatment prevented the decrease in bone mineral density and maintained the mechanical properties of bone after ovariectomy without impairing of bone mineralization in growing rats.