EFFECTS OF CONTINUOUS OR CYCLIC ADMINISTRATION OF PAMIDRONATE ON THE SKELETON IN INTACT AND OOPHORECTOMIZED YOUNG-RATS

Bisphosphonates are potent inhibitors of bone resorption, and are ther efore used for the treatment of various bone diseases including osteop orosis. We examined whether cyclic therapy with bisphosphonates in oop horectomized osteoporotic rats had any advantage over continuous treat ment. We therefore treated intact and oophorectomized young female rat s for 8 weeks with 1 and 5 mg/kg/day of pamidronate. The 8-week treatm ent was given continuously for 6 days/week or intermittently. i.e. 6 d ays of pamidronate (APD) and 3 weeks off, for 2 cycles. We found an in crease in tibial wet and ash weight and in the mineral content in ooph orectomized rats treated continuously or intermittently with APD in co mparison to nontreated oophorectomized animals. Histomorphometric anal ysis showed an increase in the volume of metaphyseal cartilage and bon e. No changes were found in the volume of epiphyseal or diaphyseal bon e. Pamidronate had very little effect on the bone of intact rats. Pami dronate seems to be more effective in inhibiting bone resorption in bo ne that undergoes rapid turnover (i.e. in oophorectomized animals) whe n compared to bone with low turnover (intact rats). Although the resul ts of cyclic treatment were similar to those of continuous treatment, we have to remember that cyclic therapy may be more advantageous since animals receiving cyclic therapy received only 25% of the dose of rat s continuously treated.