Cytokine-Mediated Inflammatory Reaction Following Posterior Cervical Decompression and Fusion Associated With Recombinant Human Bone Morphogenetic Protein-2

Abstract

Acute inflammatory reactions to rhBMP-2 can occur in the posterior cervical spine and can lead to significant morbidity. Host factors, BMP-2 dosage, and carrier factors all likely play a role in these complex reactions and must be considered every time an "off label" usage of rhBMP-2 is considered. More study is clearly indicated.

BMP2-Induced Inflammation Can Be Suppressed by the Osteoinductive Growth Factor NELL-1

“…21,22,28 Although most studies focus solely on osteogenesis and bone formation, it has been thoroughly demonstrated that BMP2 possesses inflammatory effects in addition to its osteoinductive properties. [18][19][20][21] Here we observed that BMP2 induces both acute and chronic inflammation, which is associated with increased expression of the proinflammatory cytokines TNFa and IL6. In vitro, BMP2 elicited substantial increases in generation of ROS and induction of NFkB activity.…”

“…6,7 Commonly reported adverse effects include heterotopic bone formation, 2,[8][9][10][11][12] bone resorption from osteoclast activation, [13][14][15] cyst-like bone void formation, [15][16][17] and postoperative inflammatory swelling. [18][19][20][21] In the case of anterior cervical spinal fusion, BMP2 has an estimated 40% increased risk of adverse events, including life threatening cervical swelling. 22 In fact, the FDA has issued a warning of the potential life threatening complications of BMP2.…”

Surgical seroma formation following posterior cervical laminectomy and fusion without rhBMP-2

“…In 2010, Robin et al 14 described the case of a 66-yearold patient who developed a postoperative seroma following posterior cervical decompression and fusion with rhBMP-2 for the treatment of myelopathy. They argued that rhBMP-2 set off an inflammatory cascade that included IFN-g, TNF-a, IL-1, IL-8, and MCP-1 that contributed to seroma formation.…”

“…Recently, attempts have been made to attribute the formation of spinal seromas to the use of rhBMP-2, 1,3,4,[13][14][15] which is a recombinant human protein that has been used off label to promote bone arthrodesis in patients undergoing laminectomy and spinal fusion. It is believed to act through cellular, nuclear, and cytokine signaling to induce osteoblast differentiation and thus facilitate new bone growth.…”

“…However, there have been several reports demonstrating an association between sterile postsurgical seroma formation and the use of rhBMP-2. 1,3,4,[12][13][14] Traditionally it is believed that these sterile seromas form as a result of trauma-induced inflammatory mediators that cause increased tissue capillary permeability in excess of local lymphatic drainage capacity. Surgical drainage of the fluid collection is often required, particularly in cases of neurological deterioration, and early detection is critical to prevent sequelae from cord compression.…”