Prostaglandin E2 administration prevents bone loss induced by orchidectomy in rats

Abstract
The objects of this study were to investigate whether prostaglandin E2 (PGE2) can prevent orchidectomy (ORX)‐induced cancellous bone loss in growing male rats, and to determine the differential effects of PGE2 on sham‐operated (sham) and ORX male rats. Fourteen‐week‐old Sprague‐Dawley male rats were divided into groups of basal, vehicle‐treated sham, PGE2‐treated sham, vehicle‐treated ORX, and PGE2‐treated ORX rats for either 3 or 9 weeks. PGE2 was given at 6 mg/kg body weight daily by subcutaneous injection. Static and dynamic cancellous bone histomorphometry were performed on double‐fluorescent labeled undecalcified proximal tibial metaphyseal sections. No effect was observed by ORX on body weight or longitudinal bone growth rate when compared with sham‐operated controls. However, androgen deficiency caused significant increases in percent eroded perimeter, mineral apposition rate, and bone turnover (bone‐volume‐referent‐bone formation rate), which resulted in a significant decrease in trabecular bone number, increase in trabecular separation, and a nonsignificant decrease in trabecular bone area by 3 weeks of ORX. After 9 weeks of ORX, trabecular bone area and number were significantly decreased, and trabecular separation, percent eroded perimeter, and the index of bone turnover (bone‐volume‐referent‐bone formation rate) remained significantly increased while the index of bone formation (tissue‐volume‐referent‐bone formation rate) was nonsignificantly decreased when compared with sham controls. When 6 mg PGE2kg/day was given for 3 and 9 weeks, similar anabolic effects were observed in sham and ORX rats. PGE2 caused significant decreases in body weight and longitudinal bone growth rate and significant increases in trabecular bone area, thickness, labeling perimeter, mineral apposition rate, and tissue‐volume‐referent‐bone formation rate in both sham and ORX rats when compared with their respective controls. In sham‐operated rats, PGE2 had no effect on percent eroded perimeter after 3 weeks of treatment, whereas after 9 weeks PGE2 caused a significant increase in this index. PGE2 partially inhibited the increase in percent eroded perimeter induced by ORX at week 3, but had no effect on this parameter at week 9 as compared with ORX controls. In summary, the new findings from current study indicated that PGE2 can prevent bone loss induced by ORX and the anabolic skeletal effect of PGE2 independent of the presence of androgen and longitudinal growth and occurs mainly on the pre‐existing bone surface.
Funding Information
  • National Institutes of Health ((AR-38346))
  • Department of Energy (DE-AC02-76EV00119, DE-FG02-89ER60764)