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Abstract
Background: Using agonists that selectively stimulate PGE2 receptors, the adverse effects that have limited the clinical utility of PGE2 can be avoided and there may be potential for their use as therapeutic agents in the treatment of bone loss in humans. Objective: A comprehensive review of the recent literature on the effect of prostaglandins and their agonists on bone mineral density and fracture healing. Methods: In vitro and in vivo evidence was collected using medical search engines MEDLINE® (1950 to March 2008) and EMBASE (1980 to March 2008) databases. Results/conclusion: EP4 receptors have been identified in human osteoblast cell lines and have also been shown to activate osteoblast directly and osteoclast indirectly via osteoblastic activation. Although there are strong in vitro and in vivo collective data indicating that EP2 receptors may have a role in mediating the anabolic effects of PGE2 on bone, to date no functional EP2 receptors have been identified on human osteoblasts or osteoclasts. This suggests that PGE2 effect on bone formation and resorption in humans may be governed by activation of the EP4 receptor on osteoblasts. Selective EP4 receptor agonists may therefore provide therapeutic potential for systemic use in the treatment of osteoporosis and fracture healing. Further studies need to be carried out in order fully elicit the role of EP2 receptor agonists in fracture healing and bone formation in humans.