Effects of continuous or cyclic administration of pamidronate on the skeleton in intact and oophorectomized young rats.

Abstract

Bisphosphonates are potent inhibitors of bone resorption, and are therefore used for the treatment of various bone diseases including osteoporosis. We examined whether cyclic therapy with bisphosphonates in oophorectomized osteoporotic rats had any advantage over continuous treatment. We therefore treated intact and oophorectomized young female rats for 8 weeks with 1 and 5 mg/kg/day of pamidronate. The 8-week treatment was given continuously for 6 days/week or intermittently, i.e. 6 days of pamidronate (APD) and 3 weeks off, for 2 cycles. We found an increase in tibial wet and ash weight and in the mineral content in oophorectomized rats treated continuously or intermittently with APD in comparison to nontreated oophorectomized animals. Histomorphometric analysis showed an increase in the volume of metaphyseal cartilage and bone. No changes were found in the volume of epiphyseal or diaphyseal bone. Pamidronate had very little effect on the bone of intact rats. Pamidronate seems to be more effective in inhibiting bone resorption in bone that undergoes rapid turnover (i.e. in oophorectomized animals) when compared to bone with low turnover (intact rats). Although the results 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 rats continuously treated.