Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery

Spine J. 2014 Mar 1;14(3):552-9. doi: 10.1016/j.spinee.2013.08.060. Epub 2014 Jan 8.


Background context: Recombinant human bone morphogenetic protein 2 (rhBMP-2) is a very potent osteogenic growth factor that has been used successfully in various spine fusions, obviating the need for autologous iliac crest bone graft harvest and therefore avoiding the associated morbidities.

Purpose: In the past few years, a tremendous increase in rhBMP-2 usage was noted, and concerns regarding costs, benefits, and safety issues were raised by many. The goal of this work was to provide a comprehensive review of the adverse events and complications associated with use of rhBMP-2.

Study design: Literature review.

Methods: This is a review of the current literature on the reported adverse events, complications, and concerns associated with rhBMP-2 use.

Results: This article discusses the wide spectrum of adverse outcomes related to rhBMP-2 use in the lumbar and the cervical spine; retrograde ejaculation, antibodies formation, postoperative radiculitis, postoperative nerve root injury, ectopic bone formation, vertebral osteolysis/edema, dysphagia and neck swelling, hematoma formation, interbody graft lucency, and wound healing complications are reviewed. Cost-related concerns, dosage considerations, carrier types, and theoretical carcinogenesis concerns were also presented.

Conclusions: Despite the excellent spinal fusion rates promoted by this powerful molecule, the increasingly reported adverse outcomes associated with bone morphogenetic protein usage have created real concerns. This article will provide the reader with a good understanding of the reported complications associated with rhBMP-2 use and ultimately help recognize its safety spectrum and limits for better clinical application.

Keywords: Bone morphogenetic protein; Complications; Ectopic bone; Fusion; Osteolysis; Radiculitis; Retrograde ejaculation; Spine; rhBMP-2.

Publication types

  • Review

MeSH terms

  • Bone Morphogenetic Protein 2 / adverse effects*
  • Bone Morphogenetic Protein 2 / therapeutic use
  • Cervical Vertebrae / surgery*
  • Dose-Response Relationship, Drug
  • Hematoma / epidemiology
  • Hematoma / etiology
  • Humans
  • Lumbar Vertebrae / surgery*
  • Ossification, Heterotopic / epidemiology
  • Ossification, Heterotopic / etiology
  • Radiculopathy / epidemiology
  • Radiculopathy / etiology
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Risk Factors
  • Spinal Fusion / adverse effects
  • Spinal Fusion / methods*
  • Transforming Growth Factor beta / adverse effects*
  • Transforming Growth Factor beta / therapeutic use


  • Bone Morphogenetic Protein 2
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2