CLODRONATE PREVENTS BONE LOSS IN AGED OVARIECTOMIZED RATS

The purpose of this study was to investigate the ability of clodronate to prevent ovariectomy (OVX)-induced osteopenia in aged rats. Fourtee n-month-old female Sprague-Dawley rats (n = 166) were randomized into six groups. One group was sacrificed at the start of the study, four g roups were ovariectomized, and one group was sham-operated (Sham). The OVX rats were given subcutaneously either vehicle (veh) or clodronate at doses of 3, 7, or 25 mg/kg once a week for 3 months, and the Sham rats were given the vehicle. At all dose levels clodronate inhibited t rabecular bone loss in the distal femur and in the fourth lumbar verte bral body (L4), and decreased bone resorption as evidenced by urinary deoxypyridinoline excretion. The lowest dose of clodronate preserved s erum osteocalcin and endosteal bone formation of secondary spongiosa i n L4 at the level of the Sham/veh group. The OVX-induced increase in p eriosteal bone formation of femoral diaphysis was unaffected by two sm aller doses of clodronate, but was decreased to the level of Sham rats after the highest dose, After 3 mg/kg clodronate, the percentage of f emoral cortical bone area and the mean relative cortical thickness wer e higher compared with the OVX/veh group. There was a good positive co rrelation between the maximum load in three-point bending of the tibia and tibial ash weight. Normal lamellar pattern of newly formed cancel lous and cortical bone was found after clodronate treatment, No signs of adverse accumulation of osteoid or any deleterious effect on mechan ical strength of long bones and lumbar vertebrae were found.