PROSTAGLANDIN E(2) (PGE(2)) AND RISEDRONATE WAS SUPERIOR TO PGE(2) ALONE IN MAINTAINING NEWLY ADDED BONE IN THE CORTICAL BONE SITE AFTER WITHDRAWAL IN OLDER INTACT RATS
Yf. Ma et al., PROSTAGLANDIN E(2) (PGE(2)) AND RISEDRONATE WAS SUPERIOR TO PGE(2) ALONE IN MAINTAINING NEWLY ADDED BONE IN THE CORTICAL BONE SITE AFTER WITHDRAWAL IN OLDER INTACT RATS, Journal of bone and mineral research, 12(2), 1997, pp. 267-275
The objects of this study were (1) to determine the effects of risedro
nate (Ris) and prostaglandin E(2) (PGE(2)) alone and in combination, o
n tibial diaphyses of older intact female rats; and (2) to observe the
fate of any extra bone if formed after withdrawal of the treatment. N
ine-month-old female Sprague-Dawley rats were treated with 6 mg of PGE
(2)/kg/day, 1 or 5 mu g of Ris/kg twice a week, or 6 mg of PGE(2)/kg/d
ay plus 1 or 5 mu g of Ris/kg twice a week for the first 60 days and f
ollowed by vehicle injections for another 60 days, Cross-sections of d
ouble fluorescent labeled, undecalcified tibial diaphyses proximal to
the tibiofibular junction were processed for histomorphometry. We foun
d that: (1) neither the 1 mu g nor the 5 mu g of Ris treatment in the
60-day on/60-day off group showed any histomorphometric differences fr
om age-related controls; (2) while the 60 days of PGE(2) treatment add
ed extra cortical bone (6%) on the tibial shaft (due to stimulation of
periosteal, endocortical, and marrow trabecular bone formation), the
new endocortical and most of the new marrow trabecular bone were lost
when treatment was withdrawn; however, the new periosteal bone remaine
d; (3) PGE(2) with Ris added the same amount of new bone to tibial dia
physis as did PGE(2) alone and upon withdrawal, new marrow trabecular
bone was lost but new periosteal and endocortical bones were preserved
in PGE(2) + 1 mu g of Ris on/off group, In contrast, all the new bone
was maintained in the PGE(2) + 5 mu g of Ris on/off group; (4) PGE(2)
+ Ris cotreatment failed to block the increase in cortical bone poros
ity induced by PGE(2); and (5) in the PGE(2) alone and PGE(2) + 1 mu g
of Ris on/off groups bone turnover was higher than that in the PGE(2)
+ 5 mu g of Ris on/off group, These results indicate that on/off trea
tment with PGE(2) and Ris is superior to PGE(2) alone in that it forms
the same amount of new bone during treatment, but preserves more cort
ical bone during withdrawal. Depression of bone resorption and turnove
r were the tissue mechanisms responsible for this protection.