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Evidence of Osteoinduction by Grafton Demineralized Bone Matrix in Nonhuman Primate Spinal Fusion

Louis-Ugbo, John, MD; Murakami, Hideki, MD; Kim, Hak-Sun, MD; Minamide, Akihito, MD; Boden, Scott D., MD

doi: 10.1097/01.BRS.0000090823.12652.F9
Basic Science
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Study Design.  A nonhuman primate posterolateral lumbar intertransverse process arthrodesis model was used to evaluate osteoinductive bone graft materials.

Objectives.  To test two new formulations of Grafton demineralized bone matrix (Flex and Matrix) for evidence of osteoinduction and their potential efficacy as an extender or enhancer for autogenous bone in a previously validated nonhuman primate posterolateral lumbar fusion model.

Summary of Background Data.  Whereas several demineralized bone matrix formulations have been shown to be variably osteoinductive in rodent ectopic bone assays and rabbit spine applications, few have demonstrated efficacy in higher species and in more challenging applications such as posterolateral spine fusion. The authors are not aware of any published studies describing any demineralized bone matrix that has been tested in a nonhuman primate posterolateral spine fusion model.

Methods.  After approval by the institutional animal care and use committee, eight skeletally mature rhesus macaques underwent single-level posterolateral arthrodesis. In four animals, autograft (4 g/side) was implanted with a piece of human Grafton Flex demineralized bone matrix. In the other four animals, rhesus Grafton Matrix demineralized bone matrix, a new and more porous formulation of Flex, was implanted with autograft (4 g) on one side of the spine, and Matrix with half the amount of autograft (2 g) was implanted on the opposite side. Radiographs were taken at intervals until the animals were killed at 24 weeks. Spinal fusion was evaluated by manual palpation (status was fused or not fused), and computed tomography was done to visualize the amount of bone formation.

Results.  Fusion was ascertained by palpation in two of four monkeys receiving Flex with autograft and in three of four monkeys receiving Matrix with autograft. Evidence of osteoinduction was seen in all four monkeys on the Matrix with 4 g autograft side, which had larger fusion masses than in the other treatments. Histologic examination showed that the bone formed was normal.

Conclusions  The rhesus Matrix formulation performed better than the human Flex. Evidence of osteoinduction was seen in all four monkeys that received Matrix, which improved the fusion success of autograft. This alone suggested that it might play a role as a graft enhancer, not merely as a graft extender. Human studies arewarranted.

A new form of demineralized bone matrix was successfully tested in a nonhuman primate model of posterolateral spine fusion. The new form, based on fibers of demineralized bone rather than particles, is more osteoconductive and is the first formulation to have documented efficacy in a primate model of spine fusion.

From The Emory Spine Center, Department of Orthopaedic Surgery, Emory University School of Medicine, The Atlanta Veterans Administration Medical Center, and the Yerkes National Primate Center, Atlanta, Georgia, USA.

Supported in part by Osteotech, Inc., and The Atlanta Research and Education Foundation.

The device(s)/drug(s) that is/are the subject of this manuscript is/are exempt from FDA or corresponding national regulations because they are not regulated by FDA due to minimal tissue manipulation guidelines.

Corporate/industry and Foundation funds were received to support this work. One or more of the author(s) has/have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript in the form of honoraria, gifts, consultancies, and/or royalties, stocks, stock options, decision making position.

Acknowledgment date: August 26, 2002.

Revision date: February 25, 2003.

Acceptance date: March 4, 2003.

Address correspondence to Scott D. Boden, MD, 2165 North Decatur Road, Decatur, GA 30033. E-mail: Scott_Boden@emoryhealthcare.org

© 2004 Lippincott Williams & Wilkins, Inc.