Effect of Pre- and Post-Surgery Treatment with Risedronate on Trabecular Bone Loss in Ovariectomized Rats

摘要

The purposes of the present study were to differentiate the effects of pre-surgery treatment with risedronate and post-surgery treatment with a reduced dosing frequency of risedronate on trabecular bone loss in ovariectomized rats and to determine whether post-surgery treatment with a reduced dosing frequency of risedronate would have a beneficial effect on trabecular bone loss after pre-surgery treatment with risedronate by means of bone histomorphometric analysis. The short-term experiment (6 weeks) was performed on fifty, 4-month-old, female Sprague-Dawley rats randomized into five groups (n=10 in each group). Forty rats were treated with vehicle or risedronate for 4 weeks before ovariectomy (OVX), and then treated with either vehicle or risedronate for 2 weeks following OVX (the Vehicle-OVX-Vehicle [OVX control], Vehicle-OVX-Risedronate [post-OVX treatment with risedronate], Risedronate-OVX-Vehicle [pre-OVX treatment with risedronate], and Risedronate-OVX-Risedronate [continuous treatment with risedronate] groups). The remaining 10 rats were treated with vehicle for 6 weeks, with a sham operation performed 4 weeks after the start of the experiment (the Vehicle-Sham-Vehicle [Sham control] group). During the 4 weeks prior to surgery, risedronate was administered five times a week subcutaneously at a dose of 2.5 μg /kg body weight, and during the 2 weeks after surgery, the dosing frequency was reduced to twice a week. The long-term experiment (10 weeks) had the same design as the short-term one, except that the post-OVX treatment was 6 weeks. In the short-term experiment, both pre- and post-OVX treatments with risedronate prevented trabecular bone loss of the proximal tibial metaphysis 2 weeks after OVX. In long-term experiment, however, pre- and post-OVX treatments with risedronate attenuated trabecular bone loss until 6 weeks after OVX, with pre-OVX treatment having a less pronounced effect than post-OVX treatment. In the short- and long-term experiments, pre-and post-OVX treatments had an additive effect on trabecular bone mass. The present study has shown the efficacy of pre-OVX treatment with risedronate or post-OVX treatment with a low dosing frequency of risedronate for preventing trabecular bone loss early after OVX. Post-OVX treatment with a low dosing frequency of risedronate was beneficial for attenuating trabecular bone loss late after OVX. Treatment with risedronate before OVX had an additive effect on trabecular bone mass with the treatment after OVX, suggesting that treatment with a low dosing frequency of risedronate might be acceptable for reducing OVX-induced trabecular bone loss after treatment with risedronate prior to OVX.