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Clinical significance of bone morphogenetic protein in osteosarcoma: A systematic review

Lin, James S. MD; Santiago, Juan E. MD; Mayerson, Joel L. MD; Scharschmidt, Thomas J. MD

doi: 10.1097/BCO.0000000000000804
Systematic Review

Background: The literature suggests that endogenous bone morphogenetic proteins (BMP) have both beneficial and deleterious effects on osteosarcoma. Therapeutic use of exogenous BMP after osteosarcoma resection to enhance skeletal reconstruction is controversial.

Methods: We conducted a systematic review to determine the association of endogenous BMP expression and overall survival for osteosarcoma patients to determine the association of BMP expression and metastasis, and to evaluate the extent of clinical evidence regarding use of recombinant human BMP (rhBMP) in patients with osteosarcoma.

Results: Eight studies were included; all except one reported on endogenous BMPs or BMP receptor. The four clinical studies on an association between BMPs and prognosis had mixed results; one associated BMP-7 expression with improved overall survival (OS) in osteosarcoma, while another found no correlation between BMP-6, 7, or 8 with OS. In contrast, one found a negative correlation between BMP expression and prognosis. The final study of these four investigated BMP-2 single nucleotide polymorphisms (SNP) in osteosarcoma and reported an association of a specific SNP mutation with improved prognosis. All three studies addressing metastasis reported increased risk for metastasis of osteosarcoma with either BMP-2 receptor or BMP-2 or 4 expression. Only one study evaluated application of therapeutic rhBMP-2 after osteosarcoma resection, finding no effect on clinical outcomes and no detrimental effects such as tumor recurrence.

Conclusions: Endogenous BMP or BMP receptor expression may be associated with osteosarcoma metastasis but are of uncertain prognostic significance. Any harmful or beneficial effects of exogenous therapeutic BMP application in this setting are unproven.

The Ohio State University Wexner Medical Center, Columbus, OH

Financial Disclosure: The authors report no conflicts of interest.

Correspondence to: Thomas J. Scharschmidt, MD, Associate Professor of Orthopaedics The Arthur James Cancer Hospital at The Ohio State University 725 Prior Hall Columbus, OH 43210 Tel: +614-293-4420; fax: +614-293-3747; e-mail:

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