Transpedicular Lumbar Interbody Fusion by Means of an OP-1 (BMP-7) Enhanced Hydroxyapatite Cement: A Study in the Sheep Spine**

· (a – Stryker Biotech)

Introduction: Antero-posterior procedures for the treatment of thoracolumbar burst fractures usually combine posterior instrumentation with anterior techniques that achieve primary stability for axial loading: tricortical strut-graft from the iliac crest, anterior plating-systems, or cages. In comparison to dorsal transpedicular autograft, these methods bear the burden of the additional anterior approach. Transpedicular autograft in contrast, does not prove to be clinically sufficient because of a lack of primary axial stability. In a sheep model, we therefore developed a method with posterior approach providing primary stability for axial loading. Using this model and method we tested the efficacy of the OP-1 enhanced hydroxyapatite cement to form an interbody fusion.

Methods: In 36 sheep, L4/L6 were instrumented posteriorly, intervertebral disc L4/L5 was removed under transpedicular endoscopic control via a bilateral transpedicular approach, and end plates L4/L5 were decorticated. In 12 sheep, the empty disc space was filled transpedicularly with an OP-1 enhanced hydroxyapatite cement. This composite sets after approx. 7 minutes gaining a degree of stability for axial loading which is superior to uninjured vertebrae. Another 12 sheep were treated with the hydroxyapatite cement without OP-1. The remaining 12 animals were treated with autograft. Animals were euthanized 8 weeks post op. and specimens were evaluated by means of radiological (plain X-ray and CT), histological, and histomorphometric analysis with fluorochrome labeling.

Results: Radiologically, in 10/12 cases of the OP-1 enhanced hydroxyapatite cement treated group, a solid block of OP-1 enhanced cement was seen reaching from end plate to end plate with one consistent horizontally running crack-line in the area of the former disc space. Histologically in these cases, the OP-1 enhanced cement was fully integrated at the site of the bone interface and entirely sheathed by newly formed callus. No signs of fragmentation or gross resorption of the OP-1 enhanced cement were seen in these animals. No general or local signs of inflammatory reactions were noted.

For the group treated with the hydroxyapatite cement without OP-1, bony fusion of the motion segment was seen in only 2/ 12 animals. In the fused cases, there was a solid block of cement reaching from end plate to end plate and showing one horizontal fracture line. The bone/cement integration was seen histologically at the site of the interface (entirely in 1 case, and partially in 1 case). The remaining 10 sheep showed heavy fragmentation of the cement, with gross resorption and without signs of osseous integration. Four of these animals showed severe signs of aseptic inflammatory reactions at the implantation site.

In the autograft treated group, only 10/12 sheep could be evaluated due to post op. paraplegia in 2 cases resulting in early sacrifice. In 6 of the 10 remaining sheep, a contact between the autograft and the upper end plate was seen radiologically. However, only 1/10 featured solid unilateral interbody fusion both radiologically and histologically. No general or local signs of inflammatory reactions were seen in these animals.

Discussion and Conclusions: Autograft in this model only led to a 1/10 interbody fusion rate. Hydroxyapatite cement without OP-1 (interbody fusion rate 2/12) does not seems to be superior to autograft, despite enabling primary stability for axial loading of the motion segment under investigation. Obviously, the process of biointegration of the osteoconductive cement does not proceed fast enough to make use of its primary axial stability to enhance interbody fusion. Consequently, shear-forces caused early fracture of the cement and subsequent fragmentation along with gross resorption initiating severe inflammatory reactions in 4/12 cases. The OP-1 enhanced hydroxyapatite cement cannot prevent the early horizontal fracture in the cement mass resulting from shear forces. However, the osteoinductive effects of OP-1 enhanced hydroxyapatite cement accelerated the process of biointegration of the cement resulting in full osseous integration and callus sheathing in 10/12 cases.
If compared to both control groups, transpedicular lumbar interbody fusion was successful in 10/12 cases at eight weeks post op. when the OP-1 enhanced hydroxyapatite cement was implanted (p = 0.0016). The morbidity of harvesting autograft, as well as the additional anterior surgical approach were avoided.

** The FDA has not cleared a drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed in an “off-label” use).

· If noted, the author indicates something of value received. The codes are identified as: a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options.