Association Between BMP-2 and Carcinogenicity

Spine (Phila Pa 1976). 2015 Dec;40(23):1862-71. doi: 10.1097/BRS.0000000000001126.


Study design: Literature review.

Objective: To evaluate the association between recombinant human bone morphogenetic protein-2 (rhBMP-2) and malignancy.

Summary of background data: The use of rhBMP-2 in spine surgery has been the topic of much debate as studies assessing the association between rhBMP-2 and malignancy have come to conflicting conclusions.

Methods: A systematic review of the literature was performed using the PubMed-National Library of Medicine/National Institute of Health databases. Only non-clinical studies directly addressing BMP-2 and cancer were included. Articles were categorized by study type (animal, in vitro cell line/human/animal), primary malignancy, cancer attributes, and whether BMP-2 was pro-malignancy or not.

Results: A total of 4,131 articles were reviewed. Of those, 515 articles made reference to both BMP-2 and cancer, 99 of which were found to directly examine the role of BMP-2 in cancer. Seventy-five studies were in vitro and 24 were animal studies. Forty-three studies concluded that BMP-2 enhanced cancer function, whereas 18 studies found that BMP-2 suppressed malignancy. Thirty-six studies did not examine whether BMP-2 enhanced or suppressed cancer function. Fifteen studies demonstrated BMP-2 dose dependence (9 enhancement, 6 suppression) and one study demonstrated no dose dependence. Nine studies demonstrated BMP-2 time dependence (6 enhancement, 3 suppression). However, no study demonstrated that BMP-2 caused cancer de novo.

Conclusion: Currently, conflicting data exist with regard to the effect of exogenous BMP-2 on cancer. The majority of studies addressed the role of BMP-2 in prostate (17%), breast (17%), and lung (15%) cancers. Most were in vitro studies (75%) and examined cancer invasiveness and metastatic potential (37%). Of 99 studies, there was no demonstration of BMP-2 causing cancer de novo. However, 43% of studies suggested that BMP-2 enhances tumor function, motivating more definitive research on the topic that also includes clinically meaningful dose- and time-dependence.

Level of evidence: 2.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Bone Morphogenetic Protein 2 / adverse effects*
  • Bone Morphogenetic Protein 2 / therapeutic use*
  • Humans
  • Neoplasms / epidemiology*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Spinal Fusion / adverse effects
  • Spinal Fusion / methods
  • Spinal Fusion / statistics & numerical data*
  • Spine / surgery
  • 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