Intervariability and intravariability of bone morphogenetic proteins in commercially available demineralized bone matrix products.
METHODS
Enzyme-linked immunosorbent assay was used to detect bone morphogenetic proteins (BMPs) 2, 4, and 7 in 9 commercially available ("off the shelf") demineralized bone matrix (DBM) product formulations using 3 different manufacturer's production lots of each DBM formulation.


OBJECTIVE
To evaluate and compare the quantity of BMPs among several different DBM formulations (inter-product variability), as well as examine the variability of these proteins in different production lots within the same DBM formulation (intra-product variability).


BACKGROUND
DBMs are commonly used to augment available bone graft in spinal fusion procedures. Surgeons are presented with an ever-increasing variety of commercially available human DBMs from which to choose. Yet, there is limited information on a specific DBM product's osteoinductive efficacy, potency, and constancy.


METHODS
There were protein extracts from each DBM sample separately dialyzed 4 times against distilled water at 4 degrees C for 48 hours. The amount of BMP-2, BMP-4, and BMP-7 was determined using enzyme-linked immunosorbent assay. RESULTS.: The concentrations of detected BMP-2 and BMP-7 were low for all DBM formulations, only nanograms of BMP were extracted from each gram of DBM (20.2-120.6 ng BMP-2/g DBM product; 54.2-226.8 ng BMP-7/g DBM). The variability of BMP concentrations among different lots of the same DBM formulation, intra-product variability, was higher than the variability of concentrations among different DBM formulations, inter-product variability (coefficient of variation range BMP-2 [16.34% to 76.01%], P < 0.01; BMP-7 [3.71% to 82.08%], P < 0.001). BMP-4 was undetectable.


CONCLUSIONS
The relative quantities of BMPs in DBMs are low, in the order of 1 x 10(-9) g of BMP/g of DBM. There is higher variability in concentration of BMPs among 3 different lots of the same DBM formulation than among different DBM formulations. This variability questions DBM products' reliability and, possibly, efficacy in providing consistent osteoinduction.
Bae
Hyun W
HW
Spine Research Foundation, Spine Institute at Saint John's Health Center, Santa Monica, CA 90404, USA. hbae@espineinstitute.com
Zhao
Li
L
Kanim
Linda E A
LE
Wong
Pamela
P
Delamarter
Rick B
RB
Dawson
Edgar G
EG
D001688:Biological Products / Q000737:chemistry*; D018775:Bone Demineralization Technique; D001857:Bone Matrix / Q000737:chemistry*; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D006801:Humans; D009994:Osmolar Concentration; D016212:Transforming Growth Factor beta / Q000032:analysis
C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525819:BMP7 protein, human; D001688:Biological Products; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D016212:Transforming Growth Factor beta