Complications associated with recombinant human bone morphogenetic protein use in pediatric craniocervical arthrodesis

Clinical article

Restricted access


Management of pediatric occipitocervical instability remains especially challenging. The off-label use of recombinant human bone morphogenetic protein (rhBMP)-2 for spinal fusion has increased with a well-documented increase in fusion rate in many case series. Unfortunately, recent reports have documented complications associated with rhBMP use in adult spinal fusions. Complications associated with the use of rhBMP in pediatric spinal surgery is less well understood. In this study the authors report on the fusion rate and complications associated with rhBMP in pediatric occipitocervical arthrodesis.


The authors reviewed the medical records of those patients 18 years old and younger who underwent dorsal occipitocervical fusion from January 2004 to December 2007 at the University of Iowa Hospitals and Clinics. Forty-eight patients were identified who received rhBMP-augmented fusion. The clinical outcome and complications of these fusions were analyzed.


All 48 patients had fusion confirmed on lateral radiographs within 4–14 months with an average fusion time of 6.7 months. There were 6 complications, 5 of which included seroma formation. Two of 5 patients who developed postoperative seroma presented with symptoms suggesting brainstem compression and obstructive hydrocephalus requiring emergency reoperation. One patient developed heterotopic bone formation causing cervicomedullary compression requiring reoperation.


The use of rhBMP to augment autograft in occipitocervical fusion allows for a high rate of successful arthrodesis, but is associated with potentially life-threatening complications in pediatric patients.

Abbreviations used in this paper: BMP = bone morphogenetic protein; EVD = external ventricular drain; Oc = occiput; rhBMP = recombinant human BMP.

Article Information

Address correspondence to: Arnold H. Menezes, M.D., Department of Neurosurgery, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa 52242. email:

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Case 1. An axial CT scan of the head obtained at the onset of apneic spells revealed epidural fluid in the posterior fossa and evidence of obstructive hydrocephalus (A). A sagittal MR image (B) revealed epidural fluid extending from the surgical site into the epidural space causing mass effect on the craniocervical junction. Case 2. An emergency axial CT scan of the head obtained at the onset of progressive somnolence revealed a large epidural fluid collection and obstructive hydrocephalus (C).

  • View in gallery

    Case 3. Preoperative 3D CT scans demonstrate posterior (A) and lateral (B) views of the previous suboccipital craniectomy and C-1 laminectomy. A repeat 3D CT was performed 15 months after the dorsal Oc–C2 fusion augmented with rhBMP. The posterior view (C) and superior view looking down through the foramen magnum (D) reveal extensive bone formation entirely occluding the prior decompression, causing recurrent symptoms.


  • 1

    Ahmed RTraynelis VCMenezes AH: Fusions at the craniovertebral junction. Childs Nerv Syst 24:120912242008

  • 2

    Baskin DSRyan PSonntag VWestmark RWidmayer MA: A prospective, randomized, controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the ATLANTIS anterior cervical plate. Spine (Phila Pa 1976) 28:121912252003

  • 3

    Benglis DWang MYLevi AD: A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery. Neurosurgery 62:5 Suppl 2ONS423ONS4312008

  • 4

    Boakye MMummaneni PVGarrett MRodts GHaid R: Anterior cervical discectomy and fusion involving a polyetheretherketone spacer and bone morphogenetic protein. J Neurosurg Spine 2:5215252005

  • 5

    Cahill KSChi JHDay AClaus EB: Prevalence, complications, and hospital charges associated with use of bonemorphogenetic proteins in spinal fusion procedures. JAMA 302:58662009

  • 6

    Fahim DKWhitehead WECurry DJDauser RCLuerssen TGJea A: Routine use of recombinant human bone morphogenetic protein-2 in posterior fusions of the pediatric spine: safety profile and efficacy in the early postoperative period. Neurosurgery 67:119512042010

  • 7

    Garrett MPKakarla UKPorter RWSonntag VK: Formation of painful seroma and edema after the use of recombinant human bone morphogenetic protein-2 in posterolateral lumbar spine fusions. Neurosurgery 66:104410492010

  • 8

    Lu DCSun PP: Bone morphogenetic protein for salvage fusion in an infant with Down syndrome and craniovertebral instability. Case report. J Neurosurg 106:6 Suppl4804832007

  • 9

    McKay BSandhu HS: Use of recombinant human bone morphogenetic protein-2 in spinal fusion applications. Spine (Phila Pa 1976) 27:16 Suppl 1S66S852002

  • 10

    Menezes AH: Pathogenesis, dynamics, and management of os odontoideum. Neurosurg Focus 6:6e21999

  • 11

    Meyer RA JrGruber HEHoward BATabor OB JrMurakami TKwiatkowski TC: Safety of recombinant human bone morphogenetic protein-2 after spinal laminectomy in the dog. Spine (Phila Pa 1976) 24:7477541999

  • 12

    Mimatsu KKishi SHashizume Y: Experimental chronic compression on the spinal cord of the rabbit by ectopic bone formation in the ligamentum flavum with bone morphogenetic protein. Spinal Cord 35:7407461997

  • 13

    Miyamoto STakaoka KYonenobu KOno K: Ossification of the ligamentum flavum induced by bone morphogenetic protein. An experimental study in mice. J Bone Joint Surg Br 74:2792831992

  • 14

    Ong KLVillarraga MLLau ECarreon LYKurtz SMGlassman SD: Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine (Phila Pa 1976) 35:179418002010

  • 15

    Papakostidis CKontakis GBhandari MGiannoudis PV: Efficacy of autologous iliac crest bone graft and bone morphogenetic proteins for posterolateral fusion of lumbar spine: a meta-analysis of the results. Spine (Phila Pa 1976) 33:E680E6922008

  • 16

    Paramore CGLauryssen CRauzzino MJWadlington VRPalmer CABrix A: The safety of OP-1 for lumbar fusion with decompression—a canine study. Neurosurgery 44:115111561999

  • 17

    Robertson SCMenezes AH: Occipital calvarial bone graft in posterior occipitocervical fusion. Spine (Phila Pa 1976) 23:2492551998

  • 18

    Sawin PDTraynelis VCMenezes AH: A comparative analysis of fusion rates and donor-site morbidity for autogeneic rib and iliac crest bone grafts in posterior cervical fusions. J Neurosurg 88:2552651998

  • 19

    Shahlaie KKim KD: Occipitocervical fusion using recombinant human bone morphogenetic protein-2: adverse effects due to tissue swelling and seroma. Spine (Phila Pa 1976) 33:236123662008

  • 20

    Shields LBRaque GHGlassman SDCampbell MVitaz THarpring J: Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine (Phila Pa 1976) 31:5425472006

  • 21

    Sorescu GPSykes MWeiss DPlatt MOSaha AHwang J: Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response. J Biol Chem 278:31128311352003

  • 22

    Taggard DAMenezes AHRyken TC: Instability of the craniovertebral junction and treatment outcomes in patients with Down's syndrome. Neurosurg Focus 6:6e31999

  • 23

    Urist MR: Bone: formation by autoinduction. Science 150:8938991965

  • 24

    Urist MRHuo YKBrownell AGHohl WMBuyske JLietze A: Purification of bovine bone morphogenetic protein by hydroxyapatite chromatography. Proc Natl Acad Sci U S A 81:3713751984

  • 25

    Walker DHWright NM: Bone morphogenetic proteins and spinal fusion. Neurosurg Focus 13:6e32002

  • 26

    Xiao YTXiang LXShao JZ: Bone morphogenetic protein. Biochem Biophys Res Commun 362:5505532007


Cited By



All Time Past Year Past 30 Days
Abstract Views 70 70 5
Full Text Views 39 39 0
PDF Downloads 96 96 0
EPUB Downloads 0 0 0


Google Scholar