Bone Morphogenetic Protein: The State of the Evidence of On-Label and Off-Label Use [Internet]

Excerpt

Background: Bone morphogenetic proteins (BMP) are key factors necessary for bone regeneration and healing. Recombinant DNA techniques have been used to produce BMP2 and BMP7 as alternatives to autograft bone to enhance healing of bony defects and fractures in patients where autograft bone harvest is unfeasible or contraindicated.

Currently, two rhBMPs and four associated carrier/delivery systems (one of which has been voluntarily withdrawn from the U.S. market) have received approval as devices from the U.S. Food and Drug Administration (FDA). The InFUSE® system (Medtronic Sofamor Danek, Inc.) consists of rhBMP2 on an absorbable collagen sponge carrier. OP-1® (Stryker Biotech) consists of rhBMP7 and bovine collagen, which is reconstituted with saline to form a paste. The addition of carboxymethylcellulose forms putty.

Methods: This assessment is based on an electronic search of the literature as follows:

1. MEDLINE® (January 1, 1998, through July 28, 2009)

2. EMBASE® (January 1, 1998, through July 28, 2009)

3. Cochrane Controlled Trials Register (no date restriction)

The searches were updated in February 2010.

The interventions of interest for all Key Questions (see table, following) are the use of either of the two commercially available BMP products in the U.S. Interventions were considered to be delivered on-label when administered according to the indication specified in the FDA-approved marketing label. All other uses and applications of BMP products were considered off-label.

Studies were selected to address 10 Key Questions identified for this technology assessment. In general, we abstracted data from full-length randomized, controlled trials (RCTs) and nonrandomized, comparative trials that utilized BMP therapy in patients with a bony defect that required intervention and reported at least one outcome of interest.

The quality of included studies was assessed using the general approach to grading evidence developed by the U.S. Preventive Services Task Force (USPSTF). The strength of the overall body of evidence was assessed using a framework developed by AHRQ for the EPC Methods Guide, based on a system developed by the GRADE Working Group.

Results: The electronic literature search yielded 1,992 records. Among those, 1,738 were excluded at initial title and abstract review and 254 were retrieved for full text examination. Forty-one articles describing results of comparative studies were abstracted.