Intermittent treatment of prostaglandin E2 with risedronate is more anabolic than prostaglandin E2 alone in the proximal tibial metaphysis of ovariectomized rats

This study is designed to test how intermittent application of prostaglandin E2 (PGE2) and risedronate (Ris) alone or in combination acts on the cancellous bone mass in estrogen-deficient rats. Sprague-Dawley rats were ovariectomized (ovx) or sham-ovxʹd at 6 months of age. PGE2 (6mg/kg/d), Ris (5μg/kg/twice a week) or PGE2 plus Ris were given for 60 days to ovx rats immediately after operation and followed by 60 days without treatment. The drugs were then reapplied for another 60 days. Static histomorphometry was performed on the secondary spongiosa of proximal tibial metaphysis (PTM). Sixty days of ovx lost trabecular bone and number, Ris prevented ovx-induced bone loss. PGE2 added 48% extra cancellous bone, but the new bone was completely lost after 60 days of withdrawal. Another 60 days of PGE2 treatment only partially restored the trabecular bone, the bone mass was still -42% lower than that of sham-ovx controls. Co-treatment of PGE2 with Ris added the same amount of bone as PGE2 alone after the first 60 days treatment period, but differed from PGE2 alone in that the new bone lost less during the 60 days withdrawal period. Re-application of co-treatment for another 60 days added more extra bone. We concluded that intermittent co-treatment with anabolic and anti-resorptive agents is more effective than anabolic agent alone in long-term therapy of cancellous bone in estrogen-deficient rats.