Bone Morphogenetic Proteins
Evolving technological sophistication has allowed the development of minimal access surgery. Equally exciting is the ongoing research into biologically based techniques for spinal fusion and their nascent clinical applications. Receiving particular attention from spine surgeons are the bone morphogenetic proteins (BMPs). In 1965 the existence of BMPs, a class of low-molecular-weight glycoproteins, was first proposed, and BMPs are now recognized as playing vital roles in inducing bone formation (103-105). They appear to play critical roles in the formation and maturation of skeletal tissues, with isoforms BMP-2 and BMP-7 receiving particular attention.
Naturally, the osteoinductive ability of BMPs, leading to de novo bone formation, has led to considerable interest in using these proteins to enhance spinal arthrodesis, either in concert with auto- or allograft or as stand-alone fusion inducers. Early clinical trials with recombinant human BMP-2 (rhBMP-2) have been encouraging. Boden et al. (106) compared lumbar interbody arthrodesis using autograft iliac crest vs a tapered cylindrical threaded fusion cage filled with rhBMP-2 and collagen carrier protein. The study included 14 patients with single-level lumbar degenerative disc disease refractory to nonoperative management who were randomly placed into either the rhBMP-2 group or the control autograft group. After 6 mo, radiographic arthrodesis had occurred more reliably in the rhBMP-2 group with superior outcomes measures (106). Other studies have shown successful laparoscopic ALIF fusions using rhBMP-2-soaked collagen sponges placed within tapered titanium cages (107). In addition, other authors have shown superior rates of lumbar fusion using tapered titanium fusion cages "packed" with rhBMP-2 compared with laparoscopic ALIF utilizing autologous iliac crest bone graft (108).
The demonstrated efficacy of BMP-2 for inducing bony fusion—and the absence of associated serious side effects—has led to Food and Drug Administration approval of rhBMP-2 for lumbar interbody fusion with titanium cages. Continued research will focus both on appropriate carrier matrices through which to deliver and release recombinant BMPs and the potential for rhBMP-2 delivery by gene therapy (109).
New techniques for stabilizing adjacent spinal segments while waiting for bony fusion are also emerging. Although conventional metallic spinal implants are effective in maintaining spinal alignment and preventing graft migration, they have disadvantages such as degraded imaging, occasional failure and migration, and fusion stress shielding. Thus, interest in bioabsorbable implants has emerged. Bioabsorbable polymers have several advantages: they are radi-
olucent, lack of metallic implant migration, have no of radiographic artifact, and have the ability to transfer axial loads from implant to bone as the implant degrades over time (110,111) (Fig 10). The polymers utilized most often for spinal applications are poly-lactic acid (PLA) and poly-glycolic acid (PGA).
The utility of bioabsorbable plates in anterior cervical discectomy has been demonstrated in a small number of patients. The bioabsorbable implants showed enough structural strength to maintain disc space height during the fusion process but appeared to prevent stress shielding, thereby enhancing bony fusion (112). More recent work demonstrated successful fusion in one-and two-level anterior cervical discectomies using the Macropore bioabsorbable plate and screw system (Macropore, San Diego, CA). This plate has the added benefit that the PLA construct is translucent, thereby allowing visualization of the endplates and disc space during plate application (113). In posterior appli cations, 3-yr follow-up using PLA cages in lumbar interbody fusion in animal models has shown adequate fusion and maintenance of cage height at 6 mo, as well as 50% cage reabsorption at 36 mo (114). Subach et al. (115) reported on a series of 15 patients with spondylosis or spondylolisthesis in whom bioab-sorbable cages were placed bilaterally with posterior instrumentation; 6-mo follow-up showed maintenance of disc height and foraminal diameter.
The clear advantages of a bioabsorbable system include the stability of adjacent segments during bony fusion, the eventual transfer of axial load from implant to bone as the implant degrades over time, and the avoidance of metal-related complications such as migration and imaging artifact. Larger scale studies will determine efficacy and feasibility on a statistically significant scale.
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