Partial loss of anabolic effect of prostaglandin E2 on bone after its withdrawal in rats

The object of this study was to determine the fate of PGE2-induced new bone mass after withdrawal of PGE2 administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3, and 6 mg PGE2/kg/d for 60 days and then withdrawn for 60 and 120 days. Histomorphometric analyses were performed on double fluorescent labeled undecalcified proximal tibial bone specimens. After 60 days of PGE2 treatment, a new steady state of increased trabecular bone area (+67% and +81% with 3 and 6 mg PGE2/kg/d) from woven bone and stimulated lamellar bone formation, elevated bone turnover, and shortened remodeling periods were achieved compared to age-matched controls. In contrast, after 60 and 120 days withdrawal of PGE2, a new steady state characterized by less trabecular bone area (+40% to +60% of controls with 3 and 6 mg/kg/d doses), normal lamellar bone formation, no woven bone formation from controls, and eroded surface greater than those seen in controls and previously in 60-day PGE2 treated rats. The decrease in new bone mass after withdrawal of PGE2 was due to a further elevation of bone resorption above that induced by the PGE2 treatment and a reduction in PGE2 stimulated bone formation activities. Although there is more trabecular bone than in controls after 120 days' withdrawal of PGE2, we postulate that the skeletal adaptation to mechanical usage will eventually reduce the bone mass to control levels. Thus, it is conservative to conclude that the anabolic effect of PGE2 was dependent upon continuous daily administration of PGE2 in these older rats.