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Cyst-Like Osteolytic Formations in Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Augmented Sheep Spinal Fusion

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Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro–computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2–affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone.

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Supported by California Institute for Regenerative Medicine Early Translational II Research Award TR2-01821 (K.T. and X.Z.); NIH/National Institute of Dental and Craniofacial Research grants R21 DE0177711 (C.S., K.T., and X.Z.) and RO1 DE16107-01 (C.S. and X.Z.); University of California Discovery grant 07-10677 (K.T., X.Z., and C.S.); Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Innovation Award (C.S., K.T., and X.Z.); and Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute and the National Research Foundation of Korea (NRF) grants HI16C1559 and 2016R1D1A1A02937040 (S.L.).

H.C.P., S.L., and K.T. contributed equally to this work.

X.Z. and C.S. contributed to this work equally as senior authors.

Disclosures: None declared.