Variability across ten production lots of a single demineralized bone matrix product.

Background: Demineralized bone matrix is an osteoinductive allograft derived from processed bone that is commonly mixed with autogenous bone in fusion procedures to treat diseases of the spine. An increasing number of demineralized bone matrix-based products are commercially available for spinal fusion procedures, but osteoinductive variability has been found not only across different products but also among production lots from the same demineralized bone matrix formulation. The purpose of this study was to assess the lot-to-lot variability across a single demineralized bone matrix-based product in terms of both extracted bone morphogenetic protein (BMP) concentrations (in vitro) and fusion performance in rats (in vivo). The goal was also to determine whether the in vitro measures could sufficiently and accurately predict the in vivo fusion performance of different demineralized bone matrix-based product lots.

Methods: BMP-2 and BMP-7 were extracted from ten production lots of InterGro DBM Putty and quantified with use of ELISA (enzyme-linked immunosorbent assay). A posterolateral lumbar spinal fusion was performed on forty athymic rats with implantation of a demineralized bone matrix-based product. Fusion success was determined at eight weeks with use of radiographs and manual palpation of the segments. Logistic regression was used to determine the predictive abilities of BMPs.

Results: Significant lot-to-lot variability was found in terms of both BMP concentrations (22 to 110 pg of BMP-2 per milligram of product and 44 to 125 pg of BMP-7 per milligram of product) and in vivo rates of fusion (0% to 75%; p < 0.04 for all). BMP-2 and BMP-7 concentrations correlated positively with each other across lots (r = 0.77, p < 0.0001). Most notably, extracted amounts of BMP-2 and BMP-7 each predicted in a dose-dependent manner the in vivo fusion performance in rats (R(2) = 0.32, p < 0.01 for BMP-2, and R(2) = 0.22, p < 0.009 for BMP-7).

Conclusions: Assays for demineralized bone matrix-extracted BMP-2 and BMP-7 levels may be feasible and sufficient for predicting spinal fusion performance of individual production lots from the same demineralized bone matrix-based product.