Effects of Direct Current Electrical Stimulation on Gene Expression of Osteopromotive Factors in a Posterolateral Spinal Fusion Model

In Brief Study Design. An in vivo model was used to determine levels of mRNA expression in response to direct current (DC) electrical stimulation in a rabbit posterolateral fusion model. Objectives. This study tested the possibility that DC stimulation at the surgery site would increase expression of genes related to bone formation relative to expression in autograft alone. Summary of Background Data. DC electrical stimulation as an adjunct treatment in spinal surgery has shown increased fusion rates when compared with autograft alone, yet the biology of such treatment is not fully understood. Methods. Thirty New Zealand White rabbits were entered into the study. A posterolateral, intertransverse process fusion was performed bilaterally at L4–L5, with autogenous bone graft. An implantable DC stimulator was placed across the decorticated transverse processes before placement of autograft. Animals were killed at 3, 7, 14, 21, and 28 days. mRNA levels of BMP-2, 4, 6, 7, VEGF, FGF-2, TGF-β, ALK-2, and ALK-3 were evaluated with real-time RT-PCR. Results. mRNA expression was significantly higher in the DC stimulated animals versus the control animals for several of the genes studied. In particular, levels of mRNA were elevated for BMP-2, BMP-6, and BMP-7. Conclusions. This study shows for the first time that DC stimulation results in a sustained increase of multiple osteogenic genes, suggesting that the biologic mechanism for the DC-induced increase in the rate and extent of bone formation observed clinically may be mediated by the up-regulation of these osteoinductive factors. The mechanism of action behind direct current electrical stimulation was found to involve up-regulation of the osteoinductive factors BMP-2, BMP-6, and BMP-7. These factors are normal physiologic regulators of bone formation.