PROSTAGLANDIN E(2) INCREASES THE SKELETAL RESPONSE TO MECHANICAL LOADING

The study tested the influence of prostaglandin E(2) (PGE(2)) on the s keletal response to increased in vivo mechanical loading through a fou r-point bending device, One hundred and twenty Sprague-Dawley female r ats (6 months old, 354 +/- 34 g) were divided into 12 groups to accomm odate all possible combinations of doses of loads (25, 30, or 35 N) an d PGE(2) (0, 0.1, 0.3, or 1 mg/kg), Rats received subcutaneous injecti ons of PGE(2) daily and in vivo loading of the right tibia every Monda y, Wednesday, and Friday for four weeks, Histomorphometric analysis of the periosteal and endocortical surfaces following in vivo dual fluor ochrome labeling was performed on both the loaded region of the right tibial diaphysis and a similar region of the left tibial diaphysis, Wi thout PGE(2), the threshold for loading to stimulate bone formation wa s 30 N (peak strain 1360 mu epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the endocortical surface, Without lo ading, the minimum dose of PGE(2) to stimulate bone formation at all s urfaces 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 b one formation was observed at the endocortical surface, but a synergis tic effect was noted at the periosteal surface. No combined effect of ineffective doses of loading and PGE(2) was found. A synergistic effec t at peak strains of similar to 1625 mu epsilon on the periosteal surf ace could suggest either the involvement of locally produced growth fa ctors or autoregulation of endogenous synthesis of PGE(2) by exogenous ly administered PGE(2).