• Wellington K Hsu, Mahesh Polavarapu, Rehan Riaz, Andrew C Larson, Jared J Diegmueller, Jason H Ghodasra, and Erin L Hsu.
• *Department of Orthopaedic Surgery †Departments of Radiology and Biomedical Engineering, Northwestern University Feinberg School of Medicine, Chicago, IL; and ‡Department of Research and Development, Medtronic Sofamor Danek, Inc, Memphis, TN.
• Spine. 2013 May 20;38(12):E691-8.

Study DesignProspective, randomized, controlled preclinical trial.ObjectiveThis study seeks to characterize the localized and systemic host response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a well established rodent spine arthrodesis model utilizing cytokine analysis and magnetic resonance imaging (MRI).Summary Of Background DataAlthough high fusion rates are achieved with rhBMP-2 in the spine, several complications have also been reported, including a localized response leading to radiculitis and seroma formation. The mechanism in which this occurs clinically is yet unknown.MethodsOne hundred female Fischer rats underwent a posterolateral intertransverse lumbar spinal fusion, with paraspinal muscle tissue resection, using iliac crest autograft, type I absorbable collagen sponge (ACS), 10- or 100-μg rhBMP-2/ACS. The animals underwent magnetic resonance imaging evaluation, serum cytokine analysis, manual palpation, and gross tissue inspection at 2, 4, 7, 10, and 21 days, postoperatively.ResultsQualitative evaluation of MR images demonstrated a transient fluid collection at the surgery site in the rhBMP-2 animals as early as 4 and 7 days that was greater than the autograft or ACS groups. Quantitative analysis on T2-weighted axial images demonstrated greater signal intensity in the rhBMP-2 animals compared with the ACS and autograft groups in a time-dependent fashion. Higher concentrations of several cytokines were also detected at 2, 4, and 7 days, including interleukin 1β, interleukin 18, tumor necrosis factor α, macrophage inflammatory protein 1α, and monocyte chemotactic protein 1 in animals treated with rhBMP-2/ACS relative to ACS alone.ConclusionOur data suggest that the in vivo host response to rhBMP-2 in an animal model may be associated with circulating proinflammatory and osteoclastic cytokines.

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