LOCAL STIMULATION OF NEW BONE-FORMATION BY PROSTAGLANDIN-E1 - QUANTITATIVE HISTOMORPHOMETRY AND COMPARISON OF DELIVERY BY MINIPUMPS AND CONTROLLED-RELEASE PELLETS

E-series prostaglandins (PGE) given systemically or locally in vivo can have powerful anabolic effects on bone. The comparative dose-response relationships from PGE1 given by osmotic minipump or controlled-release pellet on periosteal and intracortical bone envelopes were determined. Graded doses of PGE1 were delivered by osmotic minipump (0.0 to 16.7 mg PGE1/week) or controlled-release pellet (0.0 to 16.7 mg PGE1/week) to the lateral mandibular surface of adult dogs (2-5 years old). PGE1 was given for three weeks and tissues were collected for histology and histomorphometry one week later. At sites of maximal response, there were dose-related increases in the periosteal surface with new bone formation, average new bone thickness, maximum thickness, and new bone area. Subperiosteal bone formation was greater for comparable doses when PGE1 was delivered by minipumps. The proliferation of new bone at those sites treated with the pellets was greatest with the 8.3 mg PGE1/week/three week treatment. Periosteal bone formation did not appear to be preceded by a resorption phase, indicating that PGE1 treatment stimulated bone modeling in the formation mode. The new bone consisted of woven bone, particularly at sites with high accretion rates, and primary lamellar bone. There were some dose-related changes in intracortical remodeling indices including increases in cortical porosity, single and double-labeled surface, numbers of formation, reversal and resorption osteons, radial closure rate, and surface- and volume-referent bone formation rates. Increases in the bone formation rates indicate that PGE1 increased the recruitment of osteoblasts. Increases in the mineral appositional rate, observed at a higher dose, indicates that PGE1 stimulated bone production at the cellular level. Increased intracortical remodeling space, due to the activation of bone remodeling, was associated with an increased vascularization. These results suggest that locally delivered PGE1 may be useful in generating new bone in clinical situations of local bone deficit such as the local bone defects of the periodontal diseases and in situations where increased osteogenesis may be desired, such as with bone implants or prosthetic devices.