Prostaglandin E 2 enhances cortical bone mass and activates intracortical bone remodeling in intact and ovariectomized female rats

Abstract

To assess the efficacy of prostaglandin E 2 (PGE 2) in augmenting cortical bone mass, graded doses of PGE 2 were subcutaneously administered for 30 days to seven-month old sham-ovariectomized (SHAM) and ovariectomized (OVX) rats. Both groups were operated at three months of age. Histomorphometric analyses of double fluorescent labeled tibial shafts were performed on basal control, OVX, and SHAM rats treated with 0,0.3,1,3, and 6 mg PGE 2/kg/d for 30 days. Baseline aging data showed increased cortical tissue and cortical bone area and reduced bone formation parameters at the periosteal and endocortical bone envelopes between three and eight months of age. The tibial shafts of OVX rats compared to SHAM controls showed elevated periosteal mineral apposition rate and endocortical bone formation parameters. PGE 2 administration to OVX and SHAM rats increased cortical bone by the addition of new circumferential bone on the endocortical and periosteal surfaces, as well as woven cancellous bone in the marrow region. Stimulated osteoblastic recruitment and activity enhanced bone formation at all bone surfaces. The new bone was both lamellar and woven in nature. PGE 2 treatment also activated intracortical bone remodeling (not seen in untreated eight-month old rats), creating a porous cortex. Thus, PGE 2 administration activated cortical bone modeling in the formation mode (A→F), as well as intracortical bone remodeling (A→R→F). PGE 2 administration to OVX rats resulted in more intracortical bone remodeling, periosteal bone formation, and new cancellous bone production than observed in PGE 2 treated controls. The findings that PGE 2 administration to OVX and intact female rats increases cortical bone mass, coupled with observations that mouse, rat, dog, and man respond similarly to PGE 2, suggest that PGE 2 administration may be useful in the prevention and treatment of postmenopausal osteoporosis.