RISEDRONATE PRETREATMENT DOES NOT HAMPER THE ANABOLIC EFFECTS OF PROSTAGLANDIN E(2) IN OVX RATS

Pretreatment of an anti-resorptive agent on the anabolic effects of prostaglandin E(2) (PGE(2)) was studied on the proximal tibia and tibial shaft of ovariectomy (ovx) rats. Two days after ovx, rats were treated with either risedronate (Ris, 5 mu g/kg twice weekly) or vehicle (V) for 60 days and then switched to 3 or 6 mg/kg/d PGE(2) for 21 or 90 days. Bone area of both proximal tibial metaphysis (PTM) and tibial shaft (TX) were measured. Pretreatment with Ris increased the bone mass in PTM but not in TX of ovx rats. In the PTM, PGE(2) produced the same percentage of new bone mass in both V- and Ris- pretreated ovx rats. The amount of new bone was almost the same after 3 weeks and 12 weeks of PGE(2) treatment. There was no difference in the anabolic effects of 3 and 6 mg PGE(2)/kg/d in V-pretreated rats; however, the effects in Ris-pretreated groups were greater with 6 mg PGE(2)/kg/d than with 3 mg PGE(2)/kg/d. In TX, only the 6mg PGE(2)/kg/d administration added new bone on endocortical surfaces of both V- or Ris-pretreatment rats which leads to thickening the minimal cortical width, decreasing the marrow cavity and increasing total bone area. Both doses of PGE(2) created new trabecular bone in the marrow cavity of tibial shaft in both vehicle- and Ris-pretreated ovx rats. These results suggest that Ris-pretreatment did not hamper the anabolic effects of PGE(2) on either PTM or TX in ovx rats.