Effects of tiludronate on bone loss in the cancellous and cortical regions of Tibia in rats fed with a low calcium diet

CANCELLOUS AND CORTICAL REGIONS OF TIBIA IN RATS FED WITH A LOW CALCR]M DLET K. Aoki. t I-L Sere, t l'L Murakami, 2 M. Abe, 2 A. Barbier, 3 K. Ohya. t 'Department of Dental Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan. ~Pharmaceutieal Research Center Mciji Selka Kaisya Ltd., Yokohama, J'apan. SDepartment o f General Pharmacology, Sanofl Recherche, Montpdlier, France. Pj, trp_ osr of the study~ To evaluate how bisphosphonstes influenCe the process of bone resorption. In one experimental model for bone resorption induced by a low calcium diet in rats, bone resorption develops rapidly wi'hout affecting the growth rate. We examined the effects of disodium (4chlorophenyhhio) methylene bispbosphonate (tihidronate) in this model. Twenty 6-wnek old, male Wistar rats were assigned to 4 groups: group 1 was fed a control diet (0.5% calcium) and groups 2 to 4 were fed a low calcium diet (0.05% calcium). Phosphate content was 0.35% in both diets. All r~,ts were given subcutaneous injections for 6 days: groups 1 and 2 received vehicle alone, group 3 received 5 mgCkg/day tiludronate and group 4 had 10 mg/kg/day tiludronat=, Result: Serum levds of total and ionized calcium were normocalcemic in groups 1 and 2, but were hypocalcaemic in groups 3 and 4. Bone mineral density (BMD) in the tibia, measured by dual energy X-ray absorptiometry, decreased significandy is group 2 compared with group 1. Tiludronatr inhibited the decrease in BMD in the cancellous regions in groups 3 and 4, but did not appear to inhibit the decrease in the BMD of cortical regions. Conclusions: The regional variations in the decrease in BMD after treatment with tiludtonate might be caused by the differences in bone turnover o f cortical bone and o f trabocular bone. It seemed that the experimental period in this study was too short to observe the efficacy oftiludronate on cortical bone. Investigation should consider the regional differences in the response of bone to tiludronate during examination of the pharmacological actions of this drug.