Continuous infusion of PGE2 is catabolic with a negative bone balance on both cancellous and cortical bone in rats

X.Y. Tian (1), Q. Zhang (1), R. Zhao (1), R.B. Setterberg (1), Q.Q. Zeng (2), Y.F. Ma (2), W.S.S. Jee (1)

(1) Division of Radiobiology, University of Utah School of Medicine, Salt Lake City, UT, USA;
(2) Department of Endocrine, Musculoskeletal Research, Lilly Corporate Center, Indianapolis, IN, USA

Abstract
It is well documented that intermittent PGE2 treatment increases both trabecular and cortical bone mass. However, the effects of continuous PGE2 administration remain undocumented. The aim of the study was to investigate the effects of continuous prostaglandin E2 (PGE2) on different bone sites in skeletally mature rats. Six-month-old Sprague Dawley rats were treated with PGE2 at 1 or 3 mg/kg/d continuously via infusion pump for 21 days. Two other groups of rats received PGE2 at the same doses by intermittent (daily) subcutaneous injections and served as positive controls. Histomorphometry was performed on cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial shaft. As expected, intermittent PGE2 treatment increased both cancellous and cortical bone mass by stimulating bone formation at the cancellous, periosteal and endocortical bone surfaces. In contrast, continuous PGE2 treatment decreased cancellous bone mass with bone resorption exceeding bone formation. In addition, continuous PGE2 treatment increased endocortical and intracortical bone remodeling, inducing bone loss which was partially offset by stimulating periosteal expansion. We conclude that continuous PGE2 treatment induces overall catabolic effects on both cancellous and cortical bone envelopes, which differs from intermittent PGE2 treatment that is anabolic. Lastly, we speculate that superior bone mass may be achieved by co-treatment of continuous PGE2 in combination with an anti-catabolic agent.

Keywords: Prostaglandin E2, Bone Formation, Bone Resorption, Bone Balance