Vol. 284, Issue 1, 312-316, 1998

The Effect of Orally Administered Clodronate on Bone Mineral Density and Bone Geometry in Ovariectomized Rats

T. Österman, L. Laurén, P. Kuurtamo, R. Hannuniemi, P. Isaksson, K. Kippo, Z. Peng, H. K. Väänänen and R. Sellman

Biomedical Research Center (T.O., L.L., P.K., R.H., P.I., K.K., R.S.), Leiras Oy, Turku, Finland; Department of Anatomy and Biocenter (Z.P.), University of Oulu, Finland and Department of Medical Cell Biology (K.V.), University of Uppsala, Sweden

The effects of clodronate administered p.o. on bone mineral density (BMD), bone geometry and strength of bone were investigated in 6-month-old ovariectomized rats. Sixty Sprague-Dawley rats were randomized into four groups. Three groups were ovariectomized (OVX) and one group was sham-operated (SHAM). The OVX groups were given p.o. either clodronate (100 mg/kg/d or 500 mg/kg/d) or a vehicle. The SHAM group received the vehicle. Treatments started on the day of OVX and continued for 3 months. BMD of proximal tibial metaphysis was measured by computed tomography in vivo 1 day before OVX and 6 and 12 weeks after OVX. At the end of the study, left tibiae and femora were removed for ex vivo BMD and bone geometry measurement. A three-point bending test of the tibial shaft was carried out, and ash weights of femur and tibia were determined. OVX induced a marked decrease in total and trabecular BMD over time at the proximal tibial metaphysis. This bone loss was prevented by clodronate. Clodronate also prevented the decrease in BMD and change in bone geometry at distal and proximal femur, as well as the decrease in total ash weight of femur and tibia. OVX did not cause any marked changes in cortical BMD or bone geometry at the level of mid-diaphysis of tibia or femur over a 3-month period. Neither were there any changes between groups in bending strength in the tibial diaphysis. However, a positive correlation (n = 58, r = 0.51, P < .001) was found between bending strength and calculated density-weighted polar moment of resistance of tibial diaphysis. We conclude that clodronate administered p.o. in adult rats prevents changes due to estrogen deficiency in BMD and bone geometry.