THE EFFECTS OF CLODRONATE ON INCREASED BONE TURNOVER AND BONE LOSS DUE TO OVARIECTOMY IN RATS

The present study was carried out to investigate the ability of clodro nate to inhibit ovariectomy-induced bone loss and increased bone turno ver in rats, Estradiol was administered as a reference compound, Seven ty Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (Sha m) at the age of 90 days and divided into seven groups, Two Sham and t wo OVX groups received subcutaneously either the vehicle of clodronate or the vehicle of estradiol, Other OVX groups were given s.c. either disodium clodronate at two dose levels (5 mg/kg or 12.5 mg/kg twice a week) or 17 beta-estradiol (10 mu g/kg five times a week) for 8 weeks, Femur length, volume, dry weight, and ash weight were determined, and proximal ends of tibiae were used for bone histomorphometry, Markers of bone metabolism were measured from urine and serum, A significant l oss of 54% of trabecular bone area of proximal tibial metaphysis was f ound at 8 weeks after ovariectomy, Clodronate and estradiol inhibited (p < 0.001) this osteopenia, Both drugs prevented the decrease in ash weight! volume of the femur, The inhibitory effect of clodronate and e stradiol on bone resorption in OVX rats could be detected also in decr eased urinary excretion of hydroxyproline and lysylpyridinoline (p < 0 .001), Clodronate and estradiol decreased (p < 0.001) the ovariectomy- induced enhanced tibial endocortlcal mineral apposition rate (EI,MAR) on the lateral cortex to the level of the Sham group, In contrast, per iosteal MAR analyzed on the medial side of tibial cortical bone did no t change significantly in the OVX/Veh group, Estradiol decreased perio steal MAR to below the level in the Sham group (p < 0.01), These resul ts suggest that ovariectomy of growing rats resulted in tibial and fem oral osteopenia two months later, Clodronate as well as estradiol can suppress bone resorption and turnover in ovariectomized rats, inhibiti ng the development of osteopenia. Both clodronate doses (5 and 12.5 mg /kg) had beneficial effects in ovariectomized animals.