Co-treatment of PGE2 and risedronate is better than PGE2 alone in the long-term treatment of ovariectomized-induced osteopenic rats

We studied the effects of prostaglandin (PGE2) and risedronate (Ris) alone or in combination in 3.5-month-old intact and ovx-induced osteopenic rat skeletons to determine whether PGE2 plus Ris was more anabolic than PGE2 alone. Six mg PGE2/kg/d and 5μg Ris/kg/2x/wk alone or in combination were given to sham-ovx and ovx rats for 30 or 90 days beginning 60 days post operation. Secondary spongiosa of proximal tibial metaphyses (PTM) was studied. Ovariectomy (ovx) induced dramatic bone loss. Ris increased bone mass in sham-ovx rats and prevented further bone loss in ovx rats. PGE2 treatment for 30 days added extra bone in sham-ovx rats and no further increase after 90 days treatment. Thirty days of PGE2 alone treatment restored the bone mass in ovx rats to the level of sham-ovx rats, but the restored bone was partially lost by 90 days of treatment. Co-treatment for 30 days produced the same amount of bone mass in both sham-ovx and ovx rats as PGE2 alone did. However, unlike the PGE2 alone treated, co-treatment animals continued to form more bone for 90 days. The difference in tissue-level histomorphometry between co-treatment and PGE2 alone was that the former depressed the bone resorption and turnover. These findings indicated that the long-term administration of PGE2 alone cannot maintain or continue to add bone mass in ovx rats but that co-treatment of a PGE2 with an anti-resorptive or activation agent can resist the influence of the mechanostat induced bone loss as well as continue to add bone.