STUDY DESIGN: An experimental animal study aimed at achieving posterolateral intertransverse process fusion with rhBMP-2 in combination with the local delivery of an EP4 receptor agonist. OBJECTIVE: To determine whether an EP4 receptor agonist (EP4A) can reduce the amount of BMP required to achieve posterolateral spinal fusion in rabbits. SUMMARY OF BACKGROUND DATA: In the clinic, BMP retaining implants are used for spinal fusion and the treatment of pseudarthrosis after long bone fracture. However, the requirement of high doses of BMP-2 for bone formation in humans makes the implants expensive and limits their use in the clinic. Previous studies in our laboratory using a new delivery system involving a synthetic polymer/beta-TCP powder composite had shown it was possible to reduce the total BMP-2 amount to 30 microg per fusion in a rabbit model. To further reduce the dose of BMP required for a successful fusion, we explored the use of a chemical compound to enhance the bone-inducing action of BMP-2. METHODS: In order to prepare 1 implant to bridge the unilateral L5 and L6 transverse processes, 300 mg of polymer gel (PLA-DX-PEG block copolymer), 300 mg of beta-TCP powder, rhBMP-2 (7.5, 3.75, or 0 microg), with or without EP4A (45 microg) were mixed and manually shaped to resemble a rod. Through a posterolateral approach, 2 implants were placed on both sides (1 per side) by surgery in order to bridge the transverse processes of adult New Zealand white rabbits (n = 48). The lumbar vertebrae were recovered 6 weeks after surgery. The posterolateral fusion was examined by manual palpation, radiography, biomechanical testing, and histology. RESULTS: All of 8 rabbits that received 7.5 microg of BMP-2 and EP4A consistently showed fusion by significant amount of new bone formation. However, solid fusion was seen in only 3 of 8 rabbits that received 7.5 microg of BMP-2 without the EP4 receptor agonist. CONCLUSION: Local administration of an EP4 receptor agonist enhanced the bone-inducing activity of BMP-2 in a rabbit posterolateral lumbar spinal fusion model and as a result, the dose of BMP-2 required for this outcome was reduced by 50% compared with our previous report. The coadministration of this compound via a local delivery system may help to reduce the costs of spine fusion with use of BMP-2 in the clinic.
STUDY DESIGN: An experimental animal study aimed at achieving posterolateral intertransverse process fusion with rhBMP-2 in combination with the local delivery of an EP4 receptor agonist. OBJECTIVE: To determine whether an EP4 receptor agonist (EP4A) can reduce the amount of BMP required to achieve posterolateral spinal fusion in rabbits. SUMMARY OF BACKGROUND DATA: In the clinic, BMP retaining implants are used for spinal fusion and the treatment of pseudarthrosis after long bone fracture. However, the requirement of high doses of BMP-2 for bone formation in humans makes the implants expensive and limits their use in the clinic. Previous studies in our laboratory using a new delivery system involving a synthetic polymer/beta-TCP powder composite had shown it was possible to reduce the total BMP-2 amount to 30 microg per fusion in a rabbit model. To further reduce the dose of BMP required for a successful fusion, we explored the use of a chemical compound to enhance the bone-inducing action of BMP-2. METHODS: In order to prepare 1 implant to bridge the unilateral L5 and L6 transverse processes, 300 mg of polymer gel (PLA-DX-PEG block copolymer), 300 mg of beta-TCP powder, rhBMP-2 (7.5, 3.75, or 0 microg), with or without EP4A (45 microg) were mixed and manually shaped to resemble a rod. Through a posterolateral approach, 2 implants were placed on both sides (1 per side) by surgery in order to bridge the transverse processes of adult New Zealand white rabbits (n = 48). The lumbar vertebrae were recovered 6 weeks after surgery. The posterolateral fusion was examined by manual palpation, radiography, biomechanical testing, and histology. RESULTS: All of 8 rabbits that received 7.5 microg of BMP-2 and EP4A consistently showed fusion by significant amount of new bone formation. However, solid fusion was seen in only 3 of 8 rabbits that received 7.5 microg of BMP-2 without the EP4 receptor agonist. CONCLUSION: Local administration of an EP4 receptor agonist enhanced the bone-inducing activity of BMP-2 in a rabbit posterolateral lumbar spinal fusion model and as a result, the dose of BMP-2 required for this outcome was reduced by 50% compared with our previous report. The coadministration of this compound via a local delivery system may help to reduce the costs of spine fusion with use of BMP-2 in the clinic.
Authors: Katherine A Blackwell; Peter Hortschansky; Srdan Sanovic; Shilpa Choudhary; Lawrence G Raisz; Carol C Pilbeam Journal: Prostaglandins Other Lipid Mediat Date: 2009-09-08 Impact factor: 3.072