Intermittent on/off prostaglandin E2 and risedronate are equally anabolic as daily PGE2 alone treatment in cortical bone of ovariectomized rats.

In this study, we evaluated the rat cortical bone changes after a two-cycle, 60-day each (ON/OFF/ON/OFF) treatment with either prostaglandin E2 (OVX/c-PGE2) alone or in combination with risedronate (OVX/c-PGE2+Ris), in comparison with daily treatment with PGE2 for 240 days (OVX/PGE2-240d) in ovariectomized (OVX) rats. At the end of the study, we found that: (1) the overall effectiveness of the treatment on bone mass in the tibial shaft indicates the following ranking: OVX/PGE2-240d = OVX/c-PGE2+Ris > OVX/c-PGE2 > OVX/c-Ris > or = OVX = aging; (2) the same bone mass and architecture were produced in the OVX/PGE2-240d and the OVX/c-PGE2+Ris groups, but the histomorphometric profiles differed in that the former exhibited a higher bone turnover and index of resorption; (3) OVX/c-PGE2+Ris treatment prevented endocortical bone loss and minimized trabecular bone loss during the OFF periods; and (4) the OVX/c-PGE2 alone treatment resulted in the accumulation of less total bone than OVX/PGE2-240d and OVX/c-PGE2+Ris because it could not maintain most of the new subendocortical and marrow trabecular bone generated earlier. In summary, both continuous daily PGE2 and two cycles ON/OFF combined PGE2 and Ris treatments result in more bone mass than two cycles ON/OFF PGE2 alone and Ris alone in estrogen-deficient rats. This study showed that the anabolic effects of PGE2 can be induced and maintained either by continuous administration or by cyclical PGE2+Ris.