Prostaglandin E(2) increases the skeletal response to mechanical loading

The study tested the influence of prostaglandin E(2) (PGE(2)) on the skeletal response to increased in vivo mechanical loading through a four-point bending device, One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/- 34 g) were divided into 12 groups to accommodate all possible combinations of doses of loads (25, 30, or 35 N) and PGE(2) (0, 0.1, 0.3, or 1 mg/kg), Rats received subcutaneous injections of PGE(2) daily and in vivo loading of the right tibia every Monday, Wednesday, and Friday for four weeks, Histomorphometric analysis of the periosteal and endocortical surfaces following in vivo dual fluorochrome labeling was performed on both the loaded region of the right tibial diaphysis and a similar region of the left tibial diaphysis, Without PGE(2), the threshold for loading to stimulate bone formation was 30 N (peak strain 1360 mu epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the endocortical surface, Without loading, the minimum dose of PGE(2) to stimulate bone formation at all surfaces was 1 mg/kg/day. When 1 mg/kg/day PGE(2) was combined with the minimum effective load, an additive effect of PGE(2) and loading on bone formation was observed at the endocortical surface, but a synergistic effect was noted at the periosteal surface. No combined effect of ineffective doses of loading and PGE(2) was found. A synergistic effect at peak strains of similar to 1625 mu epsilon on the periosteal surface could suggest either the involvement of locally produced growth factors or autoregulation of endogenous synthesis of PGE(2) by exogenously administered PGE(2).