TRANSIENT EFFECTS OF SUBCUTANEOUSLY ADMINISTERED PROSTAGLANDIN-E2 ON CANCELLOUS AND CORTICAL BONE IN YOUNG-ADULT DOGS

The transient effects of prostaglandin E2 (PGE2) on cancellous and cortical bone in iliac crests and mid-tibial shafts of nine intact young adult dogs were evaluated following 31 days of treatment. Histomorphometric bone changes were characterized from in vivo fluorescent double-labeled undecalcified bone specimens. PGE2 caused an increase in cancellous bone remodeling evidenced by increased in activation frequency; increased percent eroded and formation surfaces; increased mineral apposition and bone formation rates; and shortened resorption, formation, and total bone remodeling periods. Activated cancellous bone remodeling did not lead to decreased cancellous bone mass, indicating an imbalance between bone resorption and formation in favor of formation (activation → resorption → stimulated formation; A → R → F ↑) at remodeling sites. The PGE2 treatment activated bone modeling in the formation mode (activation → formation; A → F) at the periosteal and endocortical surfaces and increased activation frequency of intracortical bone remodeling in the tibial shaft. Increased modeling activation converted quiescent bone surfaces to formation surfaces with stimulated osteoblastic activity (i.e., increased percent labeled periosteal and endocortical surfaces, mineral apposition rates, and woven and lamellar trabecular bone formation) leading to 9- to 26-fold increases in newly formed bone mass in subperiosteal, subendosteal, and marrow regions, compared to controls. However, increased intracortical bone remodeling elevated remodeling space (i.e., increased cortical porosity), producing a bone loss that partially offsets the bone gain. The combined events lead to a positive bone balance in PGE2-treated cortical bone, compared to a negative bone balance in control bones. Collectively our data suggest that in vivo PGE2 is a powerful activator of cancellous and cortical bone formation, which may be able to build a peak bone mass to prevent and/or correct the skeletal defects to cure osteoporosis. © 1990.