Stimulation of EP4 Receptor Enhanced Bone Consolidation during Distraction Osteogenesis

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The objective of this study was to confirm whether an agonist of prostaglandin E receptor subtype EP4 can enhance bone consolidation in distraction osteogenesis. A rat distraction osteogenesis model was generated.Aunilateral external fixator was fixed to the left femur of the rats of this model after osteotomy. Seven days later, 0.25 mm/12 h or 0.5 mm/12 h elongation was performed for 2 weeks. A systemic administration of an EP4 receptor agonist (ONO 4819 • CD, 3, 10, 30 μg/kg) or normal saline by subcutaneous injection was also performed for 2 weeks. The animals were sacrificed 10, 14, 17, 21, and 42 days after the operation. Radiographic examination, histological examination, and measurements of bone mineral density (BMD) and distraction-callus hardness were performed to qualitatively and quantitatively evaluate new bone formation. Twenty-one days after the operation, the experimental group had a higher BMD and a higher distraction-callus hardness than that of the control group. Forty-two days after the operation,BMDwas similar among all of the groups. But the hardness of the experimental groups increased more than that of the control group, so the statistical differences in distraction-callus hardness became more distinct between the two groups, indicating an improved remodeling of the distraction callus. These findings are also supported by histological examination. Subcutaneous injection of an EP4 receptor agonist can promote bone formation and remodeling during distraction osteogenesis. ONO 4819 •CD might be a potential candidate for shortening the treatment time of distraction osteogenesis. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:221–229, 2007

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