CLODRONATE PREVENTS OSTEOPENIA AND LOSS OF TRABECULAR CONNECTIVITY INESTROGEN-DEFICIENT RATS

Daily oral clodronate treatment was evaluated in Sprague-Dawley rats f or its ability to inhibit estrogen-deficiency-induced changes in femor al neck, femoral diaphysis, and lumbar vertebrae (LA-LS). Six-month-ol d ovariectomized (OVX) rats were administered by gavage a vehicle (Veh ) or clodronate (100 or 500 mg/kg/day). Sham-operated (SHAM) control r ats received the vehicle (n = 15/group). Treatment,vas started on the day of operation and continued for 3 months. Trabecular bone volume (B V/TV) and structural variables (trabecular number, Tb.N; thickness, Tb .Th; separation, Tb.Sp; and trabecular bone pattern factor, Tb.Pf) wer e assessed on secondary spongiosa of the right femoral neck Furthermor e, cantilever bending test of the left femoral neck and compression te st of ZA, ash weight of L5, and morphometric studies of femoral diaphy sis were carried out, and serum and urinary markers of bone turnover w ere determined. The OVX/Veh group had higher levels of serum osteocalc in and alkaline phosphatase and higher urinary excretion of deoxypyrid inoline/creatinine than the SHAM/Veh group at 3 months postsurgery, an d clodronate reduced these changes. BV/TV of femoral neck, bone mass o f L5, and the maximum loads of the femoral neck and LA were lower afte r OVX than SHAM operation. Although clodronate prevented trabecular bo ne loss in the femoral neck and preserved Tb.Pf at the SHAM control le vel, it failed to preserve the mechanical strength at the femoral neck However, in lumbar vertebrae, clodronate prevented the loss of bone m ass and mechanical properties. Furthermore, there was a good positive correlation between maximum load of L4 and the ash weight of L5 (n = 5 8, r = 0.69, p < 0.001). In the femoral neck (n = 55), Tb.Pf correlate d negatively with BV/TV and Tb.N (r = -0.59 and r = -0.55; p < 0.001, respectively) and positively with Tb.Sp (r 0.61, p < 0.001). Zn femora l mid-diaphysis, there were no significant changes in cortical bone ge ometry in any of the groups. We conclude that orally administered clod ronate suppresses the enhanced bone turnover in adult OVX rats and pre serves trabecular bone volume and connectivity in the femoral neck In the axial skeleton, clodronate has a beneficial effect on lumbar verte bral bone mass and strength.