TY - JOUR
T1 - Characterizing the host response to rhBMP-2 in a rat spinal arthrodesis model
AU - Hsu, Wellington K.
AU - Polavarapu, Mahesh
AU - Riaz, Rehan
AU - Larson, Andrew C.
AU - Diegmueller, Jared J.
AU - Ghodasra, Jason H.
AU - Hsu, Erin L.
PY - 2013/5/20
Y1 - 2013/5/20
N2 - Objective. This 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 Data. Although 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. Methods. One 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- μ g 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. Results. Qualitative 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 1 β, interleukin 18, tumor necrosis factor α, macrophage inflammatory protein 1 α, and monocyte chemotactic protein 1 in animals treated with rhBMP-2/ACS relative to ACS alone. Conclusion. Our data suggest that the in vivo host response to rhBMP-2 in an animal model may be associated with circulating proinflammatory and osteoclastic cytokines.
AB - Objective. This 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 Data. Although 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. Methods. One 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- μ g 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. Results. Qualitative 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 1 β, interleukin 18, tumor necrosis factor α, macrophage inflammatory protein 1 α, and monocyte chemotactic protein 1 in animals treated with rhBMP-2/ACS relative to ACS alone. Conclusion. Our data suggest that the in vivo host response to rhBMP-2 in an animal model may be associated with circulating proinflammatory and osteoclastic cytokines.
KW - BMP
KW - BMP-2
KW - Bone morphogenetic protein
KW - Bone resorption
KW - Complications
KW - Cytokine
KW - MRI
KW - Magnetic resonance imaging
KW - Mechanism
KW - Osteolysis
KW - RhBMP-2
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U2 - 10.1097/BRS.0b013e31828cb977
DO - 10.1097/BRS.0b013e31828cb977
M3 - Article
C2 - 23429681
AN - SCOPUS:84879076950
VL - 38
SP - E691-E698
JO - Spine
JF - Spine
SN - 0362-2436
IS - 12
ER -