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What's New in Spine Surgery

Jack E. Zigler, MD
Texas Back Institute, 6300 West Parker Road, Plano, TX 75093

Scott Boden, MD
The Emery Spine Center, 2165 North Decatur Road, Decatur, GA 30033-5307

Paul A. Anderson, MD
Orthopaedics International, 1600 East Jefferson, Suite 400, Seattle, WA98122-5698

Keith Bridwell, MD
Barnes Hospital Plaza, Suie 11300, St. Louis, MO 63110

Alexander Vaccaro, MD
925 Chestnut Street, 5th Floor, Philadelphia, PA 19107

The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. Commercial entities (Medtronic, Sulzer, Osteotech, and Wright Medical) paid or directed, or agreed to pay or direct, benefits to a research fund, foundation, educational institution, or other charitable or nonprofit organization with which one of the authors (S.B.) is affiliated or associated.

Specialty Update has been developed in collaboration with the Council of Musculoskeletal Specialty Societies (COMSS) of the American Academy of Orthopaedic Surgeons.

Sources for this annual review include the 2001 Annual Meetings of the American Spinal Injury Association, the Cervical Spine Research Society, the North American Spine Society, the Scoliosis Research Society, and the American Academy of Orthopaedic Surgeons (AAOS) as well as the Federation of Spine Associations presentations during the AAOS Specialty Day. Major contributions published in The Journal of Bone and Joint Surgery , Spine, and other selected journals during 2001 will also be discussed.

Genetic therapy and other offshoots of molecular biological research are becoming increasingly important components of the basic-science research in all areas involving the spine. Accordingly, a separate section, written by Scott Boden, MD, will be a regular addition to the yearly updates of the four traditional specialty areas involving the spine: the cervical spine, spinal deformities, the lumbar spine, and spinal injury.

What's New in the Treatment of the Cervical Spine

Cervical Disc Replacement
Early European experience with the Bryan Cervical Disc demonstrated a 79% rate of good-to-excellent results at six months and a 92% rate at one year. Patients with poor segmental mobility preoperatively did not regain motion postoperatively, suggesting that facet joint involvement may block motion at that level after insertion of the implant.

Limited English experience with the Bristol Disc, a stainless-steel ball-and-trough design, indicates that it may have some future role in the treatment of a transitional breakdown adjacent to a previous fusion, sparing the patient an extension of the fusion.

Anatomic Considerations
Bicortical fixation of the first cervical lateral mass has been described as an alternative to transarticular screws. Preoperative axial computed tomography images of the first cervical ring should be examined to determine the relationship of the internal carotid artery to the anterior aspect of the first cervical ring. In some specimens with malrotation of the first and second cervical vertebrae, the artery was <1 mm away from the anterior cortex of the atlas.

Intraoperative radiographic guidance has been used in a limited number of centers for particularly challenging cases. Woodward et al. described the use of intraoperative magnetic resonance imaging for nine patients and reported that it provided accurate and rapid localization, easy determination of screw trajectory, and confirmation of adequacy of decompression. Dandie et al. used image-guided frameless stereotaxy in complex procedures including transoral decompression, insertion of transarticular screws at the first and second cervical levels, placement of cervical and high thoracic pedicle screws, and resection of complex spinal tumors.

Vertebral artery injury during anterior cervical surgery is a rare complication, which may be associated with a more medial course of the artery. This can be noted on preoperative axial images, which should be carefully inspected to rule out an anomalous or ectatic foramen transversarium that intrudes medially into the more central area of the vertebral body1. If the artery is lacerated, tamponade should be used initially, followed by an attempt at direct repair, or ligation if the injury is unrepairable.

Surgical Management of Cervical Spondylotic Myelopathy
Chiba et al. studied the cases of seventy-six patients with cervical spondylotic myelopathy who had been treated surgically and followed for a minimum of fourteen years. Of forty-nine patients treated with anterior decompression and fusion (without internal fixation), 57% showed degenerative disc disease at adjacent levels compared with only 7% of twenty-seven treated with laminaplasty. Overall, cervical alignment and outcome tended to deteriorate over time in the patients treated with anterior surgery, and 10% of those patients ultimately required posterior salvage surgery.

Edwards and Heller retrospectively studied matched cohorts of thirteen patients each who had undergone laminaplasty or multilevel corpectomy. The duration of follow-up was three to four years. Patients treated with laminaplasty required less pain medication and had a lower perioperative complication rate. Wada et al. reported that pseudarthrosis was a major complication of corpectomy, while stiffness and axial neck pain were the main problems after laminaplasty2.

Houten and Cooper reported on twenty-eight patients with cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament treated with multilevel laminectomy and plate fixation of the lateral masses. At twenty-nine months postoperatively, 100% of the patients reported relief of sensory symptoms in the hands and 94% reported improved gait. None of the constructs failed.

Reconstruction
Fessler et al. reported the satisfactory use of anterior cervical plate fixation without posterior fixation in ninety-six patients undergoing multilevel corpectomies for degenerative or neoplastic disorders. At eighteen months postoperatively, five patients had a broken screw, but none required further treatment. No graft or plate dislodged.

Swank reported on fifty consecutive patients with cervical spinal stenosis involving three levels or more. He performed posterior decompression and posterolateral fusion with instrumentation immediately followed by anterior multilevel corpectomy, grafting, and anterior plate insertion. At an average of twenty-four months, all patients had fusion. Forty of forty-eight surviving patients had neurologic improvement, but the complication rates were high.

Epstein reported on eighty patients with diffuse cervical spondylostenosis and ossification of the posterior longitudinal ligament treated with anterior decompression. The first twenty-two patients were not treated with instrumentation, and the remaining patients had augmentation with one of three plate systems. Anterior graft extrusion occurred in three (14%) of the twenty-two patients who had not been treated with a plate. Plate and graft extrusion occurred in two (9%) of twenty-two treated with the fixed plate-fixed screw Orion system and in three (19%) of sixteen treated with the fixed plate-variable screw Atlantis system. There were no failures in twenty patients treated with dynamic ABC plates. All of the dynamic plates migrated, an average of 6.1 mm cephalad and 5.8 mm caudad.

Biomechanics
Eck et al. studied the effect of cervical spine fusion on intradiscal pressure at adjacent levels. Intradiscal pressure was measured in six cadaver spines before and after anterior plate fixation at the fifth and sixth cervical levels. After plate fixation, pressures with the cervical spine in flexion increased by 73% at the fourth and fifth cervical levels and by 45% at the sixth and seventh cervical levels. Pressures did not increase substantially at these adjacent levels with the cervical spine in extension.

Alignment
To help determine the optimal angle for fusion, Yoshimoto et al. retrospectively studied the results in seventy-nine patients following posterior arthrodesis at the first and second cervical levels. The preoperative and postoperative first and second cervical angles averaged 18.4° and 26.9°, respectively. Increased lordosis at the first and second cervical levels following surgery was compensated for by progression of the subaxial kyphosis, so that the overall alignment of the cervical spine did not change substantially. To avoid compensatory subaxial kyphosis, surgeons were urged to study the preoperative first and second cervical angles, to consider atlanto-occipital mobility, and not to cause hyperlordosis at the first and second cervical levels by approximating the spinous processes in the fusion construct.

What's New in Spinal Deformity Surgery

Idiopathic Scoliosis
There continues to be interest in the use of pedicle screws, anterior-only correction, and thoracoscopic techniques for the treatment of thoracic scoliosis. Suk et al. thought that using pedicle screws allowed the surgeon to stop at the first neutral vertebra caudally rather than at the first stable vertebra and thus spare a caudad level from fusion. Other groups pointed out that often the pedicles are very small in the upper thoracic spine and generally are smaller on the concavity, where the spinal cord tends to rest in a coronal and axial deformity.

The results of anterior fusion and instrumentation at two centers were reported to be excellent, with greater coronal and sagittal correction and less decompensation compared with what has generally been found with the posterior technique.

With regard to the thoracoscopic approach, investigators at the Texas Scottish Rite Hospital in Dallas pointed out that in many instances the tip of the screw may be very close to the aorta.

Adult Spinal Deformity
Combined anterior and posterior surgery for fixed sagittal plane deformity of the lumbar spine was advocated by a group from the University of California at San Francisco, who also noted that thoracic pseudarthrosis can usually be managed with a Smith-Petersen extension osteotomy without additional anterior surgery. A study from Baltimore demonstrated that a very high percentage of structural femoral ring allografts had incorporated by the time of a two to eight-year follow-up, suggesting that structural anterior column allograft does incorporate and maintains anterior column height in a majority of patients. Posterior vertebral column resection for the treatment of severe rigid three-dimensional deformities has been discussed by several groups. Key technical points include wide decompression and shortening of the spine.

Spondylolisthesis
There continues to be interest in the association between pelvic incidence and spondylolisthesis. Pelvic incidence, which is a combination of sacral slope and pelvic tilt, refers to the relationship between the lumbosacral junction with the pelvis and the femoral heads. Increased pelvic incidence is associated with higher-grade spondylolisthesis. Furthermore, increasing dysplasia of the posterior elements at the fifth lumbar level is associated with a higher risk of spondylolisthesis.

Congenital Scoliosis
In a study performed in San Antonio, Texas, Campbell reported on lengthening of the thoracic spine with expansion thoracoplasty, even in patients who had posterior segmental bars.

Spinal Fusion
The use of recombinant bone morphogenetic protein-2 (rBMP-2) to enhance spinal fusion has been reported at several centers. Clinical work has been promising, suggesting that fusion rates in patients treated with rBMP-2 may be slightly higher than those in patients treated with autograft. Likewise, the technique of thoracoscopically removing discs and inserting rBMP-2 to achieve fusion has seemed promising in animal models.

Braun and Ogilvie produced a tethering lordoscoliosis model in goats and demonstrated not only the ability to create apical vertebral wedge deformities in the thoracic spine but also the ability to correct them, which may ultimately allow treatment of juvenile scoliosis without the need for spinal fusion.

Biomechanics and Spinal Pelvic Fixation
Studies from Cunningham's laboratory in Baltimore have shown the benefits of using iliac fixation to protect the sacral screws in long fusion constructs. Lebwohl et al. also analyzed porous ingrowth intervertebral disc prostheses in a nonhuman primate model (twenty mature male baboons) and demonstrated ingrowth coverage of the vertebral bone-metal interface3.

Etiology
Miller et al.4 and Wise et al.5 have continued to make progress with their work on the genetics of scoliosis. Miller et al. presented evidence of an X-linked susceptibility locus, and Wise et al. discussed the positional cloning of candidate genes for familial idiopathic scoliosis. A study by Inoue from Chiba University in Japan suggests that there may be an association between estrogen receptor gene polymorphism and idiopathic scoliosis and that DNA analysis may potentially be used to predict curve progression.

Outcomes
Asher et al. and Haher have worked together to further refine the Scoliosis Research Society outcomes instrument for idiopathic scoliosis6. The SRS-24 questionnaire is now being replaced with the SRS-22 questionnaire, which appears to be reliable, valid, and responsive.

Spinal Cord Research
By providing specific nerve growth factors with use of gene therapy, Antonacci et al. achieved regeneration of central nervous system axons across a complete spinal cord injury in many of their adult rats7. In a study at Washington University in St. Louis, Yukawa et al. showed that early initiation of Bcl-2 gene transfer improved cell and tissue recovery by limiting apoptotic cell death following neural insults.

Complications
A multicenter study from Denver, Chicago, and Austin included four patients with an average age of sixty years (range, thirty-six to eighty-six years) in whom sacral insufficiency fracture developed "as a consequence of spinal instrumentation." Two patients required surgical revision. Patient selection and protection of sacral instrumentation with iliac fixation are potential considerations.

What's New in the Treatment of the Lumbar Spine

Lumbar Fusion Cages
Lumbar interbody fusion in selected individuals has been shown to reliably and effectively relieve pain in most patients with degenerative disc disease for whom conservative management has failed. A variety of surgical approaches to gain access to the intervertebral disc has been described. These include anterior, posterior, transforaminal, and combined surgical approaches.

Although anterior stand-alone cages have come under increased scrutiny over the last several years as a result of their less than satisfactory outcomes in multilevel applications, two-year follow-up data were presented on a new design that involves a tapered sagittal profile. Zdeblick and McDonough reported on 266 patients with single-level degenerative disc disease who had been treated with a laparoscopic technique involving placement of two paired, tapered, stand-alone anterior interbody cages filled with iliac crest autograft8. These patients were compared with sixty-two patients who had undergone an anterior interbody fusion with femoral ring allograft filled with iliac crest autograft. Thirteen percent of thelaparoscopic procedures required conversion to an open technique. At the time of follow-up, the group treated with thetapered cages had a 90% rate of radiographic fusion compared with a 52% rate in the control group. The improved fusion rate was associated with a higher degree of clinical improvement as assessed on the basis of Oswestry and Short Form-36 scores.

Complications related to the use of cages continues to be an area of concern. The effect of cage size, a factor that is considered paramount for optimal foraminal distraction and enhanced stability, was evaluated by Cunningham et al. In a human cadaveric study, lower lumbar spine segments were mechanically tested by applying increasing loads to the intact spine, following placement of correctly sized, paired cylindrical cages (as determined by the use of preoperative radiographic templates), and following placement of cages one size (2 mm) smaller than was appropriate. These researchers found that undersizing the cages did not substantially affect the flexion-extension stability of the construct or the overall range of motion.

Concern that cylindrical cages may inadequately confer the necessary lordosis to an instrumented interspace led to the development of tapered interbody implants. Goldstein et al. examined 111 patients treated for single-level degenerative disc disease at either the fourth and fifth lumbar levels or the fifth lumbar and first sacral levels with use of a cylindrical BAK cage. A posterior approach was used in fifty-two of these patients and an anterior approach, in fifty-nine. After two years of follow-up, the authors noted a substantial decrease in lordosis associated with the posterior approach. Clinical outcomes, however, were not substantially different between the two patient populations and were not associated with the final degree of lordosis.

There have been continued efforts to develop interbody devices that are radiolucent to allow visualization of fusion maturation while still maintaining the strength and stability needed to facilitate fusion. These efforts have led to the development of various radiolucent carbon-fiber materials and, recently, bioabsorbable implants. Outcome studies evaluating their efficacy are still in progress.

Translaminar Facet Screws
The use of stand-alone cages in patients with radiographically documented segmental instability has often resulted in early cage failure. An increasingly popular, minimally invasive strategy to enhance segmental stability following anterior cage placement is the application of adjunctive posterior translaminar facet screws. Phillips et al. performed a cadaveric study of the biomechanical contribution of adjunctive bilateral translaminar facet screws following an anterior lumbar interbody fusion9. Lumbar spine specimens were mechanically tested under physiologic loads in the intact state, following the insertion of two cylindrical BAK cages at the fifth lumbar and first sacral levels, and following the insertion of bilateral translaminar facet screws. Bilateral translaminar facet screws enhanced stability under low compressive preloads, although they offered less relative stability at higher preloads.

Transforaminal Lumbar Interbody Fusion
The transforaminal interbody approach, a relatively new approach for gaining access to the intervertebral space, was studied by several researchers. Humphreys et al. compared forty patients who had been surgically managed with that approach with thirty-four who had undergone a posterior lumbar interbody fusion over a period of thirteen months. They reported no substantial differences in blood loss, operative time, or hospital stay in the group treated with single-level fusion. However, in the group treated with multiple-level fusions, there was substantially less blood loss following the transforaminal interbody approach. Interestingly, no complications were reported following the transforaminal interbody fusion, but multiple complications were reported following the posterior lumbar interbody fusion.

Whitecloud et al. conducted a financial analysis comparing the transforaminal interbody fusion with a combined anterior-posterior approach for lumbar degenerative disc disease10. Forty patients who had undergone a one-level transforaminal interbody fusion were compared with forty patients who had undergone a one-level anterior-posterior 360° fusion. The authors noted considerably greater operative time, blood loss, and hospital stays for patients who had had the combined procedure. Use of the transforaminal interbody procedure saved, on the average, approximately $15,000 per admission.

Intervertebral Disc Replacement
The investigational use of intervertebral disc prostheses represents the frontier of surgical management of lumbar disc disease. One theoretical benefit of preserving interbody motion is a decrease in the incidence of junctional degeneration ("transitional syndrome"). These devices may improve functional outcome compared with that after motion-ablating procedures and can ultimately be revised with a fusion procedure in case of failure; results from ongoing clinical investigation are pending. Two devicesæthe SB Charité III (for single-level indications) and the ProDisc (for one and two-level disease)æare currently undergoing Food and Drug Administration-approved clinical trials in the United States.

Replacement of the nucleus pulposus is one option being developed to maintain intervertebral motion. This procedure offers the benefits of preserving the anulus fibrosus, the vertebral end plates, and the intervertebral ligaments. The Prosthetic Disc Nucleus consists of a hydrogel core encased in a woven polyethylene jacket. The device is implanted in a dehydrated state. The hydrophilic gel subsequently absorbs fluid, increasing in volume until it is restricted by the jacket. Wilke et al. reported on the biomechanical effects of this device.

A number of total disc replacement devices that generally sandwich a shock-absorbing polymer between metal end plates have been developed. The Link Charité III device consists of a nonconstrained biconvex polyethylene spacer and two separate cobalt-chromium end plates. The ProDisc uses metal-alloy end plates with midline keels to control rotation, with an ultra-high molecular weight polyethylene convex component snap-fit into the lower metal end plate.

Birnbaum et al. compared the changes in adjacent intervertebral motion between a cadaveric specimen treated with the Link Charité III disc prosthesis and a specimen treated with a single-level spinal fusion. The authors noted a 15% loss of motion at adjacent segments in the specimen with the prosthesis compared with a 60% loss in the specimen with the one-level fusion.

As with any arthroplasty implant, the potential for wear debris or inflammatory joint reaction leading to prosthetic instability is a major concern for the developers of these devices. Moore et al. reported on the effects of wear particles after experimental injection of the AcroFlex artificial disc into rats and sheep. They found that the pulverized polyolefin particles (average diameter, 3.5 m) induced a normal foreign-body reaction, similar to that seen with larger polyethylene implants. Thickening of the dura was also noted in animals in which particles had been directly layered onto the dura.

What's New in the Treatment of Spinal Cord Injury

The purpose of this discussion is to review protocols recently used to evaluate and clear the cervical spine (determine that it is free of injury) in obtunded patients. Until the cervical spine has been cleared in these patients with altered mental status, itshould be immobilized in a hard collar and special spine-related precautions should be taken. During the tertiary phase of resuscitation, the cervical spine can be more fully evaluated.

Evaluation and Clearance of theCervical Spine in Obtunded Patients
The American College of Surgeons publishes the Advanced Trauma Life Support (ATLS) manual, which includes guidelines for evaluation of the cervical spine. ATLS recommends that lateral, anteroposterior, and open-mouth cervical radiographs be made for all obtunded patients. The lateral radiograph should show the spine from the occiput to the first thoracic vertebra. When a patient has normal findings on theradiographs, the extrication collar can be removed after evaluation by an orthopaedic or neurologic surgeon. If radiographs are inadequate, a computed tomography scan should be performed. The scientific basis for these criteria was not presented in the manual.

The Eastern Association for the Surgery of Trauma (EAST) published guidelines for evaluation of the cervical spine based on a meta-analysis of the literature. When a patient is expected to have altered mental status for longer than twenty-four hours, three-view radiographs and upper cervical computed tomography are recommended. A spine is considered stable if these evaluations reveal negative findings. These guidelines were examined in a prospective study of 1356 patients with altered mental status11. All patients were evaluated with three-view plain radiographs and spiral computed tomography extending from the occiput to the third cervical level performed at the time of computed tomography of the head. The cervical computed tomography was substantially superior to plain radiographs. It identified sixty-seven of the seventy injuries, whereas the radiographs demonstrated only thirty-eight. All injuries were identified when both studies were utilized, a finding that supports the efficacy of the EAST guidelines.

Identifying Ligamentous Injuries
Chiu et al. evaluated the efficacy of the EAST guidelines for identifying ligamentous injuries in patients with altered mental status12. Their retrospective study included 14,577 patients, 614 of whom had an injury of the cervical spine. Of the patients with a cervical injury, 143 had a Glasgow coma score of <15. Fourteen of these patients had ligamentous injury, and the remaining had identifiable fractures. Plain three-view radiographs identified the ligamentious injury in thirteen of the fourteen patients, and an upper cervical computed tomography scan demonstrated it in the remaining patient. Thus, use of the EAST guidelines led to the identification of all known ligamentous injuries, which are thought to be the most likely to be missed by physical examination and on plain radiographs. However, both this study and the one described above11 were limited by an absence of follow-up data.

Potentially unstable ligamentous injuries may be missed on plain radiographs, especially in obtunded patients. Many have suggested that dynamic flexion-extension radiographs be made to identify these lesions. The ATLS manual recommends that the head and neck never be forced into flexion or extension passively. The Oxford protocol includes three-view plain radiographs, computed tomography when visualization is inadequate, and dynamic flexion-extension with use of image intensification performed by the trauma surgeon. This method led to the identification of two additional fractures inseventy-eight patients with head injury. Sees performed bedside fluoroscopy on twenty patients with a Glasgow Coma Score of <10 and negative findings on radiographs. A complete examination (visualizing the first thoracic level) was possible for only 70% of the patients. One patient was found to have an occult ligamentous injury and required surgery. Harris et al.13 performed intraoperative fluoroscopy on 153 patients undergoing surgery for other injuries. Three were found to have a previously unknown ligamentous injury. No patient in any of these three studies sustained a neurologic injury as a result of the dynamic radiographs.

Specialized Imaging Studies
Helical spinal computed tomography offers the opportunity to rapidly obtain fine-section images with reconstructions of the cervical spine at the same time as a head injury is being evaluated. As discussed above, the EAST guidelines recommend that upper cervical computed tomography be done routinely. Jelly compared computed tomography with plain radiography in a study of seventy-three patients with a head injury. Twenty patients had cervical fractures, twelve of which had occurred at the seventh cervical and first thoracic levels. Plain radiographs failed to identify five of these injuries, all of which were confirmed by computed tomography. Keenan found that helical spinal computed tomography performed at the time of computed tomography of the head substantially reduced the cost and overall number of radiographs required to clear the cervical spine in children. Barba prospectively utilized a similar protocol and found that computed tomography identified all fractures whereas plain radiographs demonstrated only 54%.

Magnetic resonance imaging is highly sensitive to acute osseous and soft-tissue injuries. However, the cost and the logistical problems of caring for a severely injured patient in ascanner have limited its use. Geck reviewed the images of eighty-nine patients with known unstable injuries. Seven were identified only by the magnetic resonance imaging. D'Alise performed magnetic resonance imaging of 121 obtunded patients who had negative or suspicious findings on radiographs. Ninety patients were found to be free of injury, and thirty-one had soft-tissue injury. Many of the injuries were trivial, although eight patients were treated with surgical stabilization.

In conclusion, obtunded patients should be carefully evaluated for occult injury of the cervical spine. These patients require three-view radiographs, and computed tomography is recommended either for areas that were poorly visualized on the plain radiographs or, according to the EAST guidelines, on a routine basis. Flexion-extension fluoroscopy, helical computed tomography, and magnetic resonance imaging may be useful in some cases. It is recommended that hospitals and trauma teams establish protocols to expeditiously clear the cervical spine in all obtunded patients.

What's New in Biological Topics for the Spine

One of the most exciting advances in the treatment of spinal disorders is related to the improved understanding of the biology of spine fusion, disc degeneration, and tissue regeneration. Moreover, an increased willingness of spine researchers to embrace the techniques of modern molecular biology and genetics is on the verge of paying large dividends in clinical practice. There are three areas with particularly notable activity in the past year: bone graft substitutes, gene therapy for spine fusion, and gene therapy for intervertebral disc disease.

Bone Graft Substitutes
Promising preclinical studies with the powerful bone morphogenetic proteins (BMPs) have led to pilot clinical trials that are just being reported at the spine societies and have not yet been subjected to careful peer review. One of the reasons BMPs can produce variable results is a suboptimal carrier or delivery matrix. Work such as that of Minamide etal. continues to highlight the importance of testing and optimizing carriers to deliver BMPs for specific spine applications14.

Expectations on the part of clinicians remain high; however, concern persists about several yet to be answered key questions. First, will the nearly 100% rate of success of BMPs seen in carefully designed preclinical trials be achieved in widespread clinical use? Will all BMPs perform similarly in the spine, or will some be better than others? Will different doses of osteoinductive protein be needed for different clinical situationsæe.g., for patients with diabetes or smokers? Will the cost be justified by direct savings derived from eliminating the need for bone graft harvest and other fusion adjuncts? What will be the role of less costly demineralized bone matrix products, some of which have begun to attain better validation in stringent spine fusion models? Time willtell.

Gene Therapy for Spine Fusion
One alternative to delivery of large quantities of recombinant or purified BMP is delivery of the gene or complementary deoxyribonucleic acid (cDNA) sequence encoding for the protein. Such a gene therapy strategy allows the patient's own cells to serve as a bioreactor and make the BMP at the site where the bone needs to be formed. Many obstacles must be overcome before this approach can be used in patients, but several groups are pursuing such gene therapy strategies.

Several investigators have reported on adenoviral delivery of cDNA for osteoinductive proteins, with varying results. These approaches have been limited by one or more of three potential drawbacks: (1) requirement of high doses of adenovirus, (2) inability to consistently form bone in immunocompetent animals, (3) a long time required to achieve viral infection (e.g., overnight), or (4) the need for complex cell isolation or expansion requiring days or weeks.

A novel approach was recently reported by Viggeswarapu et al.15. This strategy involves a ten-minute infection with very low-dose adenovirus to deliver the LIM mineralization protein-1 (LMP-1) cDNA with use of peripheral blood cells obtained at the time of surgery. Solid fusions were achieved consistently in the posterolateral aspects of the lumbar spines of adult immunocompetent rabbits. This intracellular protein appears to be active at very low doses and may induce a cascade of osteoinductive proteins, thereby requiring only a brief period of gene expression, which is ideal for gene therapy.

Gene Therapy for Intervertebral Disc Disorders
A group at the University of Pittsburgh has been active in demonstrating the ability of gene therapy, even with simple vectors such as early-generation adenovirus, to successfully express a transgene in disc cells in vitro and in vivo for prolonged periods of time. This group has also shown that intervertebral disc cells from humans can undergo gene transfer successfully16. The focus in the future will be to identify the appropriate factor or factors required to retard age-related disc degeneration, repair annular defects, and eventually regenerate intervertebral discs.

Upcoming Meetings and EventsRelated to Spine Surgery

1. The next Annual Meeting of the Scoliosis Research Society will be held on September 19, 20, and 21, 2002, at the Seattle Westin Hotel in Seattle, Washington. Fundamentals of Spine Deformity-Part 2 will be held on September 18 in Seattle.

2. The next Annual Meeting of the Cervical Spine Research Society will be held on December 5, 6, and 7, 2002, at the Fontainebleau Hilton Hotel in Miami Beach, Florida. There will be no Instructional Course at this meeting.

3. The next Annual Meeting of the North American Spine Society will take place on October 29 through November 2, 2002, in Montreal, Quebec, Canada. Spine Across the Sea, a meeting with the Japanese Spine Research Society, will be held on July 27 through 31, 2003, at the Ritz Carlton Kapalua Hotel in Maui, Hawaii. World Spine II, a combined effort with the Joint Section on Spine of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Spine and Peripheral Nerves, will be held on August 10 through 13, 2003, at the Hyatt Regency Hotel in Chicago, Illinois.

4. The Federation of Spine Associations will present the spine program at Specialty Day on Saturday, February 8, 2003, during the Annual Meeting of the American Academy of Orthopaedic Surgeons in New Orleans, Louisiana.

5. The next Annual Meeting of the American Spinal Injury Association will be held on April 4, 5, and 6, 2003, at the Intercontinental Hotel in Miami Beach, Florida. This will be a combined meeting with the Brazilian Spinal Injury Association and the Latin American Paraplegia Society.

References

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