Association Between BMP-2 and Carcinogenicity.
METHODS
Literature review.


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


BACKGROUND
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.


CONCLUSIONS
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.


METHODS
2.
*Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY †Department of Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY ‡Department of Orthopaedics and Rehabilitation, University of Wisconsin, Madison, WI.
Branko
B
Skovrlj
Steven M
SM
Koehler
Paul A
PA
Anderson
Sheeraz A
SA
Qureshi
Andrew C
AC
Hecht
James C
JC
Iatridis
Samuel K
SK
Cho
D055396:Bone Morphogenetic Protein 2 / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013123:Spinal Fusion / Q000009:adverse effects / Q000379:methods / Q000706:statistics & numerical data*; D013131:Spine / Q000601:surgery; D016212:Transforming Growth Factor beta / Q000009:adverse effects* / Q000627:therapeutic use*
D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2